Positive End‐Expiratory Pressure, Tidal Volume, and Fraction of Inspired Oxygen During General Anaesthesia in High‐Risk Patients—A Randomised Clinical Feasibility Trial

Background Optimal ventilatory settings during general anaesthesia are unknown. The goal of this trial was to test different ventilatory settings and blood pressure targets during general anaesthesia. This manuscript focuses on the ventilatory interventions. Methods This was a multicentre, randomised factorial trial conducted at eight hospitals in Denmark. Four hundred and eighty‐three patients ASA 3–5, scheduled for major surgery under general anaesthesia, were included. Patients were randomised to positive end‐expiratory pressure (PEEP) of 5, 8, or 10 cm H 2 O, tidal volume of 6, 8, or 10 mL/kg, and fraction of inspired oxygen (FiO 2 ) of 30% or 80%. The primary outcome was feasibility of delivering the ventilatory interventions, while secondary outcomes included intra‐ and postoperative complications, hospital length of stay, quality of life and recovery, and mortality. Results Feasibility goals were not met, but clear separation within each intervention was achieved. There were no differences between groups in most postoperative outcomes. Cardiac arrhythmias appeared more frequently in the PEEP‐8‐ and 10‐cm‐H 2 O groups (OR 9.32, 95% CI 1.59; 178 and OR 6.71, 95% CI 1.00; 134), compared to the PEEP‐5‐cm‐H 2 O group. Outcomes did not differ between tidal volume interventions. Pneumonia (OR 4.04, 95% CI 1.40; 14.6) and emergence delirium (OR 5.56, 95% CI 1.94; 20.4) were more frequent in patients allocated to FiO 2 of 80% than 30%. Conclusion Adherence to interventions was acceptable, although below feasibility goals. Few postoperative complications were more frequent in patients receiving PEEP 8 and 10, and in patients receiving FiO 2 of 80%. These findings should be interpreted with caution given the uncertainty of the estimates. Trial Registration: Clinicaltrials.gov: NCT06047119