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 this 28-country phase 3 RCT of 2200 thoracic surgery patients undergoing one-lung ventilation, a high PEEP plus recruitment strategy did not reduce postoperative pulmonary complications versus low PEEP without recruitment. High PEEP increased intraoperative hypotension and arrhythmias, whereas hypoxemia rescue maneuvers were more frequent with low PEEP.

Key Findings

• Primary outcome (postoperative pulmonary complications) was similar: 53.6% (high PEEP) vs 56.4% (low PEEP); absolute risk difference −2.68 pp (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%.
• Hypoxemia rescue maneuvers were more frequent with low PEEP (8.8% vs 3.3%).
• No differences in extrapulmonary postoperative complications or total adverse events between groups.

Clinical Implications

Avoid routine high PEEP with recruitment during one-lung ventilation in patients with BMI <35 kg/m2; adopt lower PEEP/permissive atelectasis with individualized rescue strategies to balance oxygenation and hemodynamics.

Limitations

• BMI ≥35 kg/m2 patients were not included, limiting generalizability to severe obesity.
• Blinding of intraoperative ventilation strategy is not feasible, potentially introducing performance bias.

Future Directions

Evaluate individualized PEEP titration and alternative lung-protective strategies in subgroups (e.g., obesity, compromised lung function) and assess longer-term pulmonary outcomes.