Background A significant reduction in regional cerebral oxygen saturation (rSO 2 ) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO 2 , pulmonary oxygenation, and hemodynamics during OLV. Methods Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP—0 cmH 2 O, 5 cmH 2 O, and 10 cmH 2 O. The primary endpoint was rSO 2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. Results After exclusion, thirty-six patients (36.11% female; age range: 60–76 year) were assigned to six groups ( n = 6 in each group). The rSO 2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO 2 ) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). Conclusions PEEP with 10 cmH 2 O makes rSO 2 decrease compared with 0 cmH 2 O. Applying PEEP with 5 cmH 2 O during OLV in elderly patients can improve oxygenation and maintain high rSO 2 levels, without significantly increasing peak airway pressure compared to not using PEEP. Trial registration Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.
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