Mechanical ventilation can cause damage by overstretching the lungs, especially when the lungs are collapsed or edematous. Raising ventilator pressures can reduce lung collapse and this can prevent overstretching from mechanical ventilation. It remains uncertain how much pressure (PEEP - positive end-expiratory pressure) should be used on the ventilator and how to identify patients who will benefit from higher ventilator pressures vs. lower ventilator pressures. The investigators are using a unique new imaging technology, electrical impedance tomography (EIT), to study this problem and to determine the safest and most effective ventilator pressure level. The results of this study will inform future trials of higher vs. lower PEEP strategies in mechanically ventilated patients.

Patients participating in this physiological cross-over randomized trial will undergo a series of PEEP maneuvers designed to assess lung recruitability, PEEP responsiveness, and optimal PEEP. EIT imaging and esophageal manometry will be employed throughout the protocol to quantify the effect of PEEP on lung function. Patients will be randomized to be ventilated at PEEP levels supplied by the ExPRESS strategy or by the EIT hyperdistention/collapse algorithm. The biological response will be assessed by measuring serum cytokines.

Inclusion Criteria:

• Acute (≤7 days) hypoxemia with PaO2:FiO2 ratio less than or equal to 200 mm Hg
• Oral endotracheal intubation and mechanical ventilation
• Bilateral airspace opacities on chest radiograph or CT

Exclusion Criteria:

• Contraindication to EIT electrode placement (burns, chest wall bandaging limiting electrode placement)
• Contraindication to esophageal catheter placement (recent upper GI surgery, actively bleeding esophageal varices)
• Respiratory failure predominantly due to cardiogenic cause or fluid overload
• Ongoing hemodynamic instability (requiring 2 vasopressor agents by continuous infusion AND rising vasopressor infusion rate requirements in the previous 8 hours)
• Ongoing ventilatory instability (P/F < 70 mm Hg, pH < 7.2; ventilator driving pressures, PEEP, or FiO2 increasing by more than 25% in previous 30 minutes)
• Intracranial hypertension (suspected or diagnosed by medical team)
• Known or suspected pneumothorax recognized within previous 72 hours
• Bronchopleural fistula
• Bridge to lung transplant
• Recent lung transplantation (within previous 6 weeks)
• Attending physician deems the transient application of high airway pressures (>40 cm H2O) to be unsafe