Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome

Inclusion Criteria: 1. Age ≥ 18 years 2. Ventilator-dependent ARDS, with all of the following (a-e): 1. Invasive ventilation with positive end-expiratory pressure (PEEP) ≥ 8 cm H2O or FiO2 ≥ 0.5 2. Hypoxemia as characterized by: • If arterial blood gas (ABG) available: the partial pressure of oxygen in the arterial blood (PaO2)/FiO2 ≤ 300 mm Hg, or, • if ABG not available OR overt clinical deterioration in oxygenation since last ABG: SpO2/FiO2 ≤ 316 with SpO2 ≤ 97% (both conditions) on two representative assessments between 1 to 6 hours apart. • If patient is positioned prone or receiving inhaled pulmonary vasodilator at time of screening: Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) that was recorded within the 6 hours immediately prior to initiating either of these therapies may be used for eligibility determination. • If PEEP has been increased by \> 5 cm H2O within the last 12 hours immediately prior to screening: Qualifying PaO2/FiO2 or SpO2/FiO2 (as defined above) prior to PEEP increase may be used for eligibility determination if recorded within this 12-hour window. 3. Bilateral lung opacities on chest imaging not fully explained by effusions, lobar collapse, or nodules 4. Respiratory failure not fully explained by heart failure or fluid overload 5. Onset within 1 week of clinical insult or new/worsening symptoms 3. Early in ARDS course * Full criteria for ARDS (#2 above) first met within previous 3 days * Current invasive ventilation episode not more than 4 days duration * Current severe hypoxemic episode (receipt of invasive ventilation, noninvasive ventilation, or high-flow nasal cannula) not more than 10 days duration Exclusion Criteria: 1. Esophageal manometry already in use clinically 2. Severe brain injury: including suspected elevated intracranial pressure, cerebral edema, or Glasgow coma score (GCS) ≤ 8 directly caused by severe brain injury (e.g., ischemia or hemorrhage) 3. Gross barotrauma or chest tube inserted to treat barotrauma (note: chest tube inserted strictly for drainage of pleural effusion is not an exclusion) 4. Esophageal pathology that, in judgement of the site investigator, significantly increases risk of esophageal catheter placement, including high-risk esophageal varices, recent oropharyngeal or gastroesophageal surgery; or past esophagectomy 5. Ongoing severe coagulopathy (platelet \< 5000/μL or INR \> 4) 6. Extracorporeal membrane oxygenation (ECMO) or CO2 removal (ECCO2R) 7. Neuromuscular disease that impairs spontaneous breathing (including but not limited to amyotrophic lateral sclerosis, Guillain-Barré syndrome, spinal cord injury at C5 or above) 8. Any of the following severe chronic lung diseases: cystic fibrosis, acute bronchiectasis exacerbation, acute exacerbation of a chronic interstitial lung disease (ILD), chronic pulmonary hypertension (PH) on PH-targeted vasoactive medication, or lung transplant 9. End-stage chronic cirrhosis with Child-Pugh Class C (Section 12.3) 10. ICU admission for burn injury 11. Current ICU stay \> 2 weeks or acute care hospital stay \> 4 weeks 12. Moribund patient not expected to survive 24 hours as assessed by the study physician; if cardiopulmonary resuscitation (CPR) was provided, assessment for moribund status must occur at least 6 hours after CPR was completed 13. Current limitation on life-sustaining care (other than do-not-resuscitate), or expectation by clinical team that a limitation on life-sustained care will be adopted within next 24 hours. 14. Treating clinician refusal or unwilling to use protocol-specified ventilator settings/modes 15. Prisoner 16. Previous enrollment in this trial