PROtective Ventilation With FLOW-Controlled Ventilation to Improve Postoperative Pulmonary Outcome After THORACic Surgery - an International Multicenter Pilot Randomized Clinical Trial

The PROFLOW-THORACic pilot trial is an international multicenter randomized clinical pilot trial designed to evaluate the feasibility and safety of flow-controlled ventilation (FCV) during thoracic surgery requiring one-lung ventilation (OLV). The study specifically investigates whether FCV can be consistently and safely applied during all phases of intraoperative ventilation, particularly during OLV, across multiple international centers, and whether the study protocol itself is feasible for a future large-scale randomized clinical trial evaluating postoperative pulmonary outcomes. The trial further aims to generate exploratory clinical data regarding postoperative pulmonary complications (PPCs) and to provide the methodological foundation for a definitive efficacy trial. The study protocol was developed by the Department of Anaesthesiology, Rescue- and Pain Medicine at HOCH Health Ostschweiz, Cantonal Hospital St. Gallen, Switzerland, in collaboration with several international thoracic anesthesia centers.

Postoperative pulmonary complications remain among the most important causes of perioperative morbidity and mortality following thoracic surgery. Patients undergoing open, video-assisted, or robot-assisted thoracic procedures are particularly susceptible to pulmonary injury because of the physiologic challenges associated with OLV. During OLV, only one lung is ventilated while the contralateral lung is intentionally collapsed to facilitate surgical exposure. This results in reduced functional lung volume, impaired respiratory mechanics, ventilation-perfusion mismatch, increased airway pressures, and heterogeneous ventilation distribution. Despite advances in perioperative care and the implementation of lung-protective ventilation strategies using lower tidal volumes and moderate levels of PEEP, PPCs remain frequent after thoracic surgery and are associated with prolonged hospitalization, increased ICU admission, and higher mortality. Conventional ventilation strategies during OLV often require elevated inspired oxygen concentrations, recruitment maneuvers, and adjustments of airway pressures to maintain adequate oxygenation, potentially contributing to ventilator-induced lung injury, atelectasis, hemodynamic instability, and cyclic alveolar collapse.

Flow-controlled ventilation represents a novel ventilation mode that fundamentally differs from conventional pressure- or volume-controlled ventilation. FCV delivers constant inspiratory and expiratory flow throughout the entire respiratory cycle, resulting in linear changes in airway pressure and volume. In contrast to conventional ventilation modes, expiration during FCV is actively controlled rather than passive. Experimental and early clinical studies suggest that FCV may improve lung recruitment, optimize ventilation homogeneity, reduce cyclic alveolar collapse, and improve gas exchange. Preclinical studies demonstrated reductions in inflammatory lung injury and improved respiratory mechanics, while small clinical studies in obese patients and thoracic surgery patients reported improved oxygenation and carbon dioxide elimination compared with conventional ventilation. However, current evidence remains limited to small physiologic studies and single-center experiences. Therefore, before conducting a larger efficacy trial evaluating the impact of FCV on patient-centered postoperative outcomes, the feasibility and safety of implementing FCV in a multicenter thoracic surgery setting must first be established.

The PROFLOW-THORACic pilot trial is designed as a prospective, randomized, controlled pilot study involving multiple international centers in Switzerland, Austria, Germany, France, and the Netherlands. A total of 140 patients undergoing elective thoracic surgery requiring OLV will be enrolled. Patients will be randomized in a 1:1 ratio to either receive FCV or conventional volume-controlled ventilation (VCV). Randomization will be stratified by center using a block randomization process. The study follows a single-blinded design in which patients remain blinded to group allocation, while anesthesiologists cannot be blinded because different ventilators are required for the two ventilation strategies.

Eligible participants are adult patients aged 18 years or older who are scheduled for elective open, video-assisted, or robot-assisted thoracic surgery requiring OLV using a double-lumen tube and who are able to provide written informed consent. Major exclusion criteria include severe pulmonary disease such as COPD GOLD stage III or IV, severe emphysema, pulmonary fibrosis, pulmonary hypertension, previous lung surgery, planned postoperative mechanical ventilation, severe cardiac disease, intracranial pathology, bilateral thoracic procedures, pregnancy, and pre-existing severe respiratory failure or hypercapnia. The study specifically excludes patients with conditions that could substantially increase perioperative respiratory risk or interfere with interpretation of pulmonary outcomes.