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

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.

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.

Eligibility Criteria:
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)