Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

Study Overview
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Brief Summary
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The study investigates the role of positive pressure, inspired oxygen fraction and different decubiti (seated, supine, prone) on breathing effort (as assessed by esophageal pressure swings) in Covid-19 pneumonia (at different disease stages) and in other causes of respiratory failure. The hypothesis is that positive pressure might be deleterious in terms of breathing effort if the main pathological mechanism associated with Sars-CoV-2 infection in the lung is not alveolar damage (as in other causes of respiratory failure) but vascular impairment as previously reported. The effects of high inspired oxygen fractions and decubiti might also be different with respect to other causes of respiratory failure.

Detailed Description
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In spite of the overwhelming numbers of the current pandemic, many questions remain open regarding the pathophysiology of Covid-19 associated pneumonia. While some features of the disease (such as the oxygenation improvement associated with proning and/or continuous positive airway pressure) seem to line up with other causes of pneumonia characterized by primary alveolar damage, specific characteristics have been reported about Sars-CoV-2 lung infection which suggest a certain degree of parenchymal preservation and a predominant role of vascular impairment: the dissociation between lung volume and gas exchange, and the so called happy hypoxemia both evoke the possibility of mechanisms other than the loss of aeration as causes of hypoxia. Accordingly, evidence are now growing on the role of vascular dysregulation in this regard. It is probable, as previously put forward, that different stages exist in the disease which may account for the discordant findings of previous studies seeking to either associate or separate Covid-19 pneumonia and other causes of respiratory failure. In the present study we will compare the effects of three currently used approaches to improve gas exchange (continuous positive airway pressure, external oxygen administration and decubiti variations) in three different populations (1) early Covid-19 pneumonia, 2) severe late Covid-19 pneumonia and 3) non-Covid-19 pneumonia) in terms of breathing effort as assessed by esophageal pressure swings: our aim is to evaluate, in these populations, the real benefits (beyond the previously reported ones on gas exchange) of such strategies on lung rest. Our hypothesis is that, at least in the early stages of Covid-19 (and as opposed to other causes of respiratory failure), the application of positive pressure might be deleterious if no potential for recruitment, but rather a primary vascular impairment, is associated with hypoxia. If this will be the case the same (or a similar) degree of oxygenation improvement and a safer pattern of ventilation might be attained with the simple administration of oxygen or decubiti variations without the application of positive pressure, thus completely changing the current standards for the treatment of Covid-19 pneumonia.

Official Title
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Dynamic Transpulmonary Pressure in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Device: Esophageal catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1 (Covid-19 early pneumonia) Age > 18 Positive Sars-CoV 2 nasal swab interstitial pneumonia at either CT scan or chest X-ray Respiratory failure requiring CPAP for less than 48 hours FiO2 ≤0.5 and CPAP≤10 cmH2O Group 2 (Covid-19 severe pneumonia) Age > 18 Positive Sars-CoV 2 nasal swab interstitial pneumonia at either CT scan or chest X-ray Respiratory failure requiring CPAP Signs of severity with CPAP 10 cmH2O and FiO2 0.5: pulse oximetry (SpO2) ≤ 93% associated to either: Dyspnea Two or more signs of increased respiratory effort (respiratory rate ≥25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35) Group 3 (Non Covid-19 pneumonia) Age > 18 Negative Sars-CoV 2 nasal swab CT scan or chest X-ray non compatible with Covid-19 associated pneumonia Respiratory failure requiring CPAP Exclusion Criteria: Group 1 (Covid-19 early pneumonia) Concomitant chronic pulmonary disease Chronic heart failure New York Heart Association (NYHA) 3-4 Bacterial pulmonary associated infection (diagnosed or suspected) Pulmonary embolism Acute cardiogenic pulmonary edema Signs of severity with CPAP 10 cmH2O and FiO2 0.5: SpO2≤ 93% associated to either: Dyspnea Two or more signs of increased respiratory effort (respiratory rate ≥25 bpm, use of accessory inspiratory muscles , tirage, intercostal space depression, nasal flaring, expiratory abdominal efforts, PaCO2 < 35) At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration) Group 2 (Covid-19 severe pneumonia) Concomitant chronic pulmonary disease Chronic heart failure NYHA 3-4 Bacterial pulmonary associated infection (diagnosed or suspected) Pulmonary embolism Acute cardiogenic pulmonary edema At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration) Group 3 (Non Covid-19 pneumonia) Concomitant chronic pulmonary disease Chronic heart failure NYHA 3-4 Bacterial pulmonary associated infection (diagnosed or suspected) Pulmonary embolism Acute cardiogenic pulmonary edema At least one sign of respiratory fatigue/decompensation (pH<7.30 with PaCO2 >45, respiratory rate <15 bpm, paradoxal abdominal breathing, mental status alteration)

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spontaneous breathing, Venturi Mask FiO2 0.5, seated decubitus<br>Patient will be evaluated after 20 minutes of spontaneous breathing, with FiO2 0.5 (Venturi Mask), during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Spontaneous breathing, Non Rebreathing Mask, seated decubitus<br>Patient will be evaluated after 20 minutes of spontaneous breathing, with FiO2 1 (Non Rebreathing Mask), during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, seated decubitus<br>Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, supine decubitus<br>Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during supine decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 0.5, prone decubitus<br>Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 0.5, during prone decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 7 cmH2O, FiO2 1, seated decubitus<br>Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 1.0, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 0.5, seated decubitus<br>Patient will be evaluated after 20 minutes of CPAP (12 cmH2O), with FiO2 0.5, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|
| Experimental: Continuous Positive Airway Pressure (CPAP) 12 cmH2O, FiO2 1, seated decubitus<br>Patient will be evaluated after 20 minutes of CPAP (7 cmH2O), with FiO2 1.0, during seated decubitus. Respiratory, haemodynamics, and data on blood gas analysis will be obtained. | Device: Esophageal catheter<br>* Patients are equipped with an esophageal catheter: positioning is performed after accurate nasopharyngeal anesthesia with lidocaine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal pressure swings at different levels of positive end-expiratory pressure (PEEP) | The main outcome of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three levels of end expiratory pressure applied (0-7-12 cmH2O) | 160 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal pressure swings at different levels of inspired oxygen fraction | One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the two levels of FiO2 applied (0.5-1) | 160 minutes | 
| Esophageal pressure swings at different decubiti | One of the secondary outcomes of the study is represented by the difference in esophageal pressure swings (expiratory minus inspiratory) between the three decubiti applied (seated, supine, prone) | 160 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Pneumonia, Esophageal Pressure, Respiratory Drive