Inhaled Sevoflurane for ARDS Prevention

longitudinal evolution in the PaO2/FiO2 ratio

Progression to ARDS will be assessed according to the Berlin criteria, including chest radiographs

Pneumonia will be defined according to the 3 following criteria:

• Two chest radiographs showing signs of pneumonia, or one in absence of cardiomyopathy or underlying pulmonary condition.
• One item among: body temperature ≥38.3°C without evident cause, leukocytes <4000/mm3 or ≥12000/mm3
• Two items among: purulent secretions, cough or dyspnea, increased need for oxygen supplementation or ventilatory assistance.

Ventilator free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or dies prior to day 28, VFDs will be zero.

Organ failure is defined as present when the most abnormal vital signs or clinically available lab value meets the definition of clinically significant organ failure according to SOFA scores. Patients will be followed daily from randomization to day 5 for development of organ failures.

The occurrence of death in the ICU will be recorded until day 28.

The total number of days from admission to ICU discharge will be recorded until day 28

• Oxygenation Index on study days 1-5

• PaCO2 on study days 1-5

• Arterial pH on study days 1-5

• Level of PEEP (and static auto-PEEP in patients under controlled ventilation) on study days 1-5

• Plateau pressure, static compliance of the respiratory system on study day 1-5

• Development of pneumothorax through day 28

• Time to switching from controlled to pressure-support ventilation through day 5

• Airway occlusion pressure at 0.1 s (P0.1), an index of respiratory drive, on the day the patient is switched to pressure-support ventilation if within 5 days since randomization

• Hemodynamic measures (mean arterial pressure, dose of infused norepinephrine or other vasopressor, serum lactate level) on study days 1-5

• KDIGO criteria for acute kidney injury 24 through day 5

• Supraventricular tachycardia (SVT) or new onset atrial fibrillation through day 5

The Confusion Assessment Method for the ICU (CAM-ICU, Appendix C )97 will be assessed daily from study entry to study day 28, death or ICU discharge, whichever comes first.

Plasma samples will be collected from indwelling catheters (when available) at study entry and on days 1, 2, 3, 4, 5 in order to assemble a biological collection aimed at further investigating the effects of inhaled sedation with sevoflurane in patients with ARDS.

The investigators will also collect whole blood samples at study entry and on day 2 for future studies of macrophage activation profiles and RNA and DNA studies.