The search for the missing link between better physiology and patient outcomes: a reply

We thank Mukherjee and Elwakil for their thoughtful and constructive comments [1] on our study [2]. We agree that improvements in intra-operative physiological variables do not necessarily translate into improved clinical outcomes, which remains one of the central challenges in peri-operative lung-protective ventilation research. We acknowledge that most patients in our study were ASA physical status 2 with relatively preserved pulmonary function, and therefore our findings may not be applicable directly to frail or higher-risk populations. However, we believe this observation is clinically informative. Although individualised positive end-expiratory pressure (PEEP) improved respiratory mechanics and oxygenation, postoperative pulmonary complications were not reduced. This suggests that, in many older thoracic surgical patients with relatively preserved pulmonary reserve, current conventional lung-protective strategies may already provide sufficient protection. Under such circumstances, transient intra-operative physiological improvements may not necessarily translate into additional clinical benefit. We also agree that the composite postoperative pulmonary complication endpoint may have reduced sensitivity to detect ventilation-related effects, particularly as prolonged air leak is influenced predominantly by surgical and parenchymal factors rather than ventilatory management alone. Nevertheless, we selected this endpoint because of its widespread use and clinical relevance in peri-operative pulmonary research [3]. We would also like to clarify that the control group in our study received fixed PEEP of 5 cmH2O together with recruitment manoeuvres before transitions between one-lung and two-lung ventilation, reflecting our routine contemporary clinical practice. Therefore, our study should not be interpreted as a comparison between protective and non-protective ventilation, but rather between a conventional lung-protective strategy and an electrical impedance tomography-guided individualised approach. Our findings suggest that, in older thoracic surgical patients with relatively preserved pulmonary function, further escalation of PEEP guided by physiological optimisation may improve intra-operative respiratory variables without necessarily reducing postoperative pulmonary complications. Regarding dynamic titration, we agree that respiratory mechanics evolve continuously during thoracic anaesthesia. However, repeated electrical impedance tomography-guided titration may present important practical limitations in routine clinical practice, including workflow complexity, interruption of surgical progress and potential haemodynamic consequences. Our intention was therefore not to establish a continuously adaptive ventilation model, but rather to evaluate a pragmatic and clinically implementable individualised strategy.