EPVent 2- A Phase II Study of Mechanical Ventilation Directed by Transpulmonary Pressures

Inclusion Criteria: * Acute onset of ARDS as defined by the Berlin Consensus Conference definitions: 1. Hypoxemic respiratory failure with PaO2 / FIO2 ratio \< 200 mmHg 2. b) Bilateral alveolar/interstitial infiltrates on chest x-ray, with opacities not present for more than 7 days 3. Respiratory failure not fully explained by cardiac failure or fluid overload 4. Intubation on controlled ventilation and receiving PEEP ≥ 5 cm H2O * Age 16 years or older * Duration of ARDS 36 hours or less from meeting final Berlin criterion. Exclusion Criteria: * Received mechanical ventilation more than 96 hours * Recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement * Severe coagulopathy (platelet count \< 5000/microliter or INR \> 4) * History of lung transplantation * Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided * Evidence of active air leak from the lung * not committed to full support * Participation in other intervention trials for ARDS or for sepsis within the past 30 days. * Neuromuscular disease that impairs ability to ventilate spontaneously * Severe chronic liver disease, defined as Child-Pugh Score of ≥12 * Treating clinician refusal, or unwillingness to commit to controlled ventilation for at least 24 hours * Inability to get informed consent from the patient or surrogate. * Use of rescue therapies for prior to enrollment (e.g. nitric oxide, ECMO, prone positioning, high frequency oscillation). This does not exclude cases where these therapies were used as the initial mode of ventilation