Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial.

Summary

In a 74-site international Phase 3 RCT of 2200 thoracic surgery patients undergoing one-lung ventilation, higher PEEP with recruitment did not reduce postoperative pulmonary complications compared with lower PEEP without recruitment. High PEEP increased intraoperative hypotension and arrhythmias, while hypoxemia rescue maneuvers were more frequent in the low PEEP group.

Key Findings

• Primary outcome (postoperative pulmonary complications) did not differ: 53.6% (high PEEP) vs 56.4% (low PEEP); absolute risk difference -2.68 percentage points (95% CI -6.36 to 1.01); p=0.155.
• High PEEP increased intraoperative complications: hypotension 37.3% vs 14.3% and new arrhythmias 9.9% vs 3.9% compared with low PEEP.
• Extrapulmonary postoperative complications and total adverse events were similar between groups.

Clinical Implications

Avoid routine use of higher PEEP with recruitment during one-lung ventilation in patients with BMI <35; prefer lower PEEP with permissive atelectasis and individualized rescue maneuvers, with vigilant hemodynamic monitoring if higher PEEP is considered.

Limitations

• Generalizability limited by exclusion of patients with BMI ≥35 kg/m².
• Hemodynamic instability with high PEEP may confound interpretation of net clinical benefit in some subgroups.

Future Directions

Define optimal individualized PEEP targets during one-lung ventilation, integrate real-time hemodynamic/oxygenation monitoring, and assess outcomes in obese populations and high-risk subgroups.