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Tidal Volume and Positive End-expiratory Pressure and Postoperative Hypoxemia during General Anesthesia: A Single-center Multiple Crossover Factorial Cluster Trial

Background: Intraoperative mechanical ventilation is a major component of general anesthesia. The extent to which various intraoperative tidal volumes and positive end-expiratory pressures (PEEP) effect on postoperative hypoxia and lung injury remains unclear. We hypothesized that adults having orthopedic surgery, ventilation using different tidal volumes and PEEP levels affect the oxygenation within first hour in the postoperative care unit. Methods: We conducted a two-by-two factorial crossover cluster trial at the Cleveland Clinic Main Campus. We enrolled patients having orthopedic surgery with general anesthesia who were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. The primary outcome was the effect of tidal volume or PEEP on time-weighted average peripheral oxygen saturation measured by pulse oximetry divided by the fraction of inspired oxygen (Spo2/Fio2 ratio) during the initial postoperative hour. Results: We enrolled 2,860 patients who had general anesthesia for orthopedic surgery from September 2018 through October 2020. The interaction between tidal volume and PEEP was not significant (P = 0.565). The mean ± SD time-weighted average of Spo2/Fio2 ratio was 353 ± 47 and not different in patients assigned to high and low tidal volume (estimated effect, 3.5%; 97.5% CI, –0.4% to 7.3%; P = 0.042), for those assigned to high and low PEEP (estimated effect, –0.2%; 97.5% CI, –4.0% to 3.6%; P = 0.906). We did not find significant difference in ward Spo2/Fio2 ratio, pulmonary complications, and duration of hospitalization among patients assigned to various tidal volumes and PEEP levels. Conclusions: Among adults having major orthopedic surgery, postoperative oxygenation is similar, with tidal volumes between 6 and 10 ml/kg and PEEP between 5 and 8 cm H2O. Our results suggest that any combination of tidal volumes between 6 and 10 ml/kg and PEEP between 5 versus 8 ml cm H2O can be used safely for orthopedic surgery. A total of 2,860 orthopedic surgical patients having general anesthesia were assigned in a 2 x 2 factorial cluster trial to 6 versus 10 ml/kg tidal volume and to 5 versus 8 cm H2O PEEP. There was no interaction between VT and PEEP. The primary outcome, the Spo2/Fio2 ratio, was similar in each tidal volume and PEEP group. Secondary outcomes including postoperative oxygenation, duration of hospitalization, and composite pulmonary complications also did not differ significantly. Tidal volumes between 6 and 10 ml/kg and PEEP between 5 and 8 cm H2O are similar with respect to pulmonary outcomes.