Ultraprotective Ventilation Without Extracorporeal Circulation During COVID 19 Pneumonia

For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.

All-cause mortality with analysis in intention to treat, i.e. each patient will be analyzed in his initial randomization group regardless of whether the allocated strategy was effectively applied or not.

VFD will be computed as follows from the day of inclusion:

VFD= 0 if the patient dies between inclusion and day 60 VFD = 60-x if the patient is successfully weaned from invasive mechanical ventilation x days after inclusion. Successful weaning from mechanical ventilation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) VFD= 0 if the patient is mechanically ventilated for more than 60 days after inclusion

Per protocol analysis will be carried out by comparing the group of patients in whom median daily tidal volume from inclusion to weaning of deep sedation will be lower of equal to 4.2 ml/kg of predicted body weight to the group of patients in whom median tidal volume from inclusion to weaning of deep sedation will be greater than 4.2 ml/kg of predicted body weight, whatever the patients' initial randomization group.

Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

Successful extubation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) Data will be right censored at 60 days and death will be taken into account as a competing risk.

Data will be right censored at 90 days and death will be taken into account as a competing risk.

Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

Doses of the following drugs used for deep sedation will be assessed daily: midazolam, propofol and opioid. Opioid dose will be expressed as morphine equivalent with the following conversion factor: 1µg of sufentanil = 10 µg of fentanyl = 1 mg of morphine

Rescue therapies are any therapy among the following ones: neuromuscular blocking agents, prone position, nitric oxide, recruitment maneuvers, ECMO

Severe mixed acidosis is defined by the association of pH<7.15 and PaCO2>45 mm Hg.

Ventilator associated pneumonia will be defined as any pneumonia acquired under mechanical ventilation after inclusion.

Acute cor pulmonale is defined by the association of right ventricle dilatation (right ventricle surface / left ventricle surface >0,6) and septal dyskinesia assessed by echocardiography

Barotrauma is defined by any pneumothorax OR pneumomediastinum OR subcutaneous emphysema, OR pneumatocele of more than 2 cm detected on image examinations.

Serious adverse event is any life threatening event OR any event resulting in death.

The Telephone Montreal Cognitive Assessment score will be assessed by phone call. The total score ranges from 0 to 30; higher scores being associated to a better outcome.

The RAND 36-Item Health Survey (SF-36) score will be assessed by phone call. The score ranges from 0 to 100; higher scores being associated to a better outcome.

The Impact of Event Scale - revised (IES-R) score will be assessed by phone call. The total score ranges from 0 to 88; higher scores being associated to a worse outcome.

The cost-efficacy ratio will be computed as the ratio of cost difference on efficacy difference between the intervention arm and the reference arm. The costs taken into account will be the direct hospitalized costs. The efficacy will be assessed as the number of days alive free from mechanical ventilation.