Esophageal balloon catheter placed within 4 hours of randomization. PEEP titrated to achieve end-expiratory transpulmonary pressure of 0-2 cmH2O (up to 8 cmH2O for P/F ratio <200). PEEP adjusted in 2 cmH2O increments with 5-minute stabilization periods. Safety limits: transpulmonary driving pressure <15 cmH2O, end-inspiratory transpulmonary pressure <20 cmH2O. Reassessment twice daily (approximately 0800 and 2200). Catheter removed prior to extubation or at 28 days, whichever occurs first.

PEEP management according to current standard practice. For patients meeting ARDS criteria, PEEP titrated using the ARDSNet PEEP/FiO2 table. For non-ARDS patients, PEEP titrated per local practice to optimize oxygenation while monitoring hemodynamic tolerance and respiratory mechanics. No esophageal pressure monitoring.

PEEP titration guided by transpulmonary pressure measurements using esophageal manometry. Esophageal balloon catheter inserted within 4 hours of randomization, positioned at 35-40 cm depth with position verified by cardiac oscillations and occlusion test. PEEP titrated in 2 cmH2O increments targeting end-expiratory transpulmonary pressure 0-2 cmH2O, with option to target up to 8 cmH2O for severe hypoxemia (P/F <200). Safety limits enforced: transpulmonary driving pressure <15 cmH2O, end-inspiratory transpulmonary pressure <20 cmH2O. Measurements performed twice daily. Catheter removed at extubation or day 28.

Composite feasibility assessment including: (1) Recruitment rate (patients enrolled per month, target 1-1.5/month); (2) Successful esophageal catheter placement rate in intervention arm; (3) Protocol adherence (percentage of scheduled transpulmonary pressure measurements completed, compliance with PEEP titration algorithm); (4) Data completeness for average PEEP over 7 days.

Key secondary endpoint. Mean positive end-expiratory pressure during mechanical ventilation

Difference in driving pressure between groups

Occurrence of esophageal catheter complications (perforation, bleeding)