HemodynamIc eFfects of Lung Collapse and overdIstension During ARDS

• Change in PEEP (Other): Patients will undergo a decremental PEEP trial to determine the crossing-point PEEP. Secondly, three PEEP levels (low collapse PEEP, low overdistention PEEP and crossing point between lung collapse and overdistention PEEP) will be compared in a randomized order with 30-minute steps

Primary outcomes

• Impact of lung collapse on cardiac output [Assesment performed at the end of each of the three 30 minute steps]: Evaluation of the relative contribution of lung collapse (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
• Impact of lung collapse on pulmonary vascular resistance [Assesment performed at the end of each of the three 30 minute steps]: Evaluation of the relative contribution of lung collapse (arbitrary units) on pulmonary vascular resistance (dyn·s/cm\^5) at different PEEP levels
• Impact of lung overdistention on cardiac output [Assesment performed at the end of each of the three 30 minute steps]: Evaluation of the relative contribution of lung overdistention (arbitrary units) on patients' cardiac output at different PEEP levels (L/min)
• Impact of lung overdistention on pulmonary vascular resistance [Assesment performed at the end of each of the three 30 minute steps]: Evaluation of the relative contribution of lung overdistention (arbitrary units) on pulmonary vascular resistance (dyn·s/cm\^5) at different PEEP levels

Secondary outcomes

• Correlation between potential for lung recruitment and PEEP-induced changes in cardiac output [Assessment at the end of each of the three 30 minute steps]: The effects of PEEP on cardiac output (mL/min) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)
• Correlation between potential for lung recruitment and PEEP-induced changes in pulmonary vascular resistance [Assesment performed at the end of each of the three 30 minute steps]: The effects of PEEP on pulmonary vascular resistance (dyn·s/cm\^5) will be correlated through Pearson correlations with the individual potential for lung recruitment, as determined by the recruitment-to-inflation ratio (R/I)
• PEEP-induced effects on cardiac output in cardiac preload responsive vs. nonresponsive patients [Assesment performed at the end of each of the three 30 minute steps]: The effects of PEEP on cardiac output (L/min) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload responsiveness assessed through pulse-pressure variation, expressed in %)
• PEEP-induced effects on pulmonary vascular resistance in cardiac preload responsive vs. nonresponsive patients [Assesment performed at the end of each of the three 30 minute steps]: The effects of PEEP on pulmonary vascular resistance (dyn·s/cm\^5) will be compared through subgroup comparisons (student t-test) in patients who are preload responsive and patients who are not (preload resposnsiveness assessed through pulse-pressure variation, expressed in %)
• Relationship between transpulmonary pressures and central venous pressure variations [At the end of each of the three 30 minute steps]: The relationship between transpulmonary pressure variations (cmH2O) and central venous pressure variations (cmH2O) between PEEP levels will be assessed through Pearson correlations
• Lung hysteresis [At the end of each of the three 30 minute steps]: Lung hysteresis will be assessed at each of the tested PEEP levels and expressed as the area of the pressure-volume loop of the respiratory system obtained with a low-flow inflation/deflation maneuver from PEEP to a pressure of 30 cmH2O, in mL*cmH2O
• Lung aeration distribution [At the end of each of the three 30 minute steps]: Lung aeration distribution at each PEEP level tested will be assessed with electrical impedance tomography (EIT) and expressed as dorsal fraction of ventilation (% of total tidal volume)
• Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in pulmonary vascular resistance [Assesment performed at the end of each of the three 30 minute steps]: The effects of PEEP on pulmonary vascular resistance (dyn·s/cm\^5) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)
• Relationship between PEEP-induced changes in lung volume and PEEP-induced changes in cardiac output [Assesment performed at the end of each of the three 30 minute steps]: The effects of PEEP cardiac output (L/min) will be correlated through Pearson correlations with the individual PEEP-induced changes in lung volume (mL)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* acute respiratory failure with onset < 1 week from a predisposing risk factor, such as pneumonia, non-pulmonary infection, trauma, transfusion, aspiration, or shock;
* bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on lung ultrasound not fully explained by effusions, atelectasis, or nodules/masses;
* pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload, and hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis;
* PaO2/FiO2 ratio ≤ 200 during invasive controlled mechanical ventilation;

Exclusion Criteria:

* age <18 years;
* pregnancy;
* signs of barotrauma or documented pneumothorax;
* severe tachycardia (HR > 120 bpm) and severe lacticaemia (lac > 4 mmol/L)
* pre-existing decompensated heart failure (NYHA class 3-4 and/or documented left ventricular ejection fraction < 35%);
* contraindications to EIT placing (open chest wounds, presence of cardiac pacemaker);
* intubation as a result of an acute exacerbation of chronic pulmonary disease;
* contraindications to esophageal balloon placement (high bleeding risk, esophageal varices).

• Domenico Luca Grieco, MD, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS