Ultraprotective Ventilation Without Extracorporeal Circulation During COVID 19 Pneumonia

Mortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O).

Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.


Eligibility Criteria:
Inclusion Criteria:

* Adults aged 18 years or older
* ARDS according to the Berlin definition
* COVID-19 pneumonia confirmed by RT-PCR
* Acute respiratory failure not fully explained by left ventricular failure or sodium overload
* Bilateral pulmonary radiological opacities not fully explained by pleural effusions or atelectasis or nodules
* Invasive mechanical ventilation with PaO2/FiO2 ≤ 150 mm Hg and PEEP ≥ 5 cm H2O with a tidal volume below or equal to 6 ml per kilogram of predicted body weight
* Continuous intravenous sedation as part of ARDS treatment

Exclusion Criteria:

* Exclusion criteria related to ARDS history

  * ARDS onset more than 48 hours before inclusion
  * previous inclusion in present study
* Exclusion criteria related to ARDS severity or complications

  * arterial pH \< 7.21 despite respiratory rate set to 35/min at the time of inclusion
  * patient under any extracorporeal CO2 removal technique or ECMO
  * pneumothorax or bronchopleural fistula
* Exclusion criteria related to comorbidities

  * suspected intracranial hypertension
  * severe chronic obstructive pulmonary disease defined by a GOLD score ≥ 3
  * chronic respiratory failure under home oxygen or non-invasive ventilation
  * chronic respiratory failure requiring long term oxygen or non-invasive ventilation
  * obesity with body weight over height ratio greater than 1 kg/cm
  * sickle cell disease
  * bone marrow transplant \< 6 months
  * burn injury with extension greater than 30% of body surface area
  * cirrhosis with Child-Pugh score C
  * advance directives to withhold or withdraw life sustaining treatment
* Exclusion criteria related to legislation

  * Patient under an exclusion period relative to participation to another clinical trial, or inclusion into a clinical trial interfering with the ventilatory strategies
  * pregnancy, lactating women
  * patient under a legal protective measure.
  * lack of affiliation to social security as required by French regulation
  * lack of written informed consent by patient or next of kin (unless if recourse to the emergency procedure in the absence of a loved one)