BACKGROUND The main concern regarding lung-protective ventilation strategies during neurosurgery is the reduction in venous return and increase in cerebral blood flow when using high positive end-expiratory pressure (PEEP). This study aimed to evaluate and compare the changes in regional cerebral oxygen saturations (rSO2) during the use of 5 cmH₂O and 10 cmH₂O PEEP in patients undergoing craniotomy for tumor resection. MATERIAL AND METHODS The study was designed as a prospective, single-blind randomized controlled study. Patients aged between 18 and 70 years, scheduled for an elective craniotomy for tumor resection, were divided into 2 groups: 5 cmH₂O PEEP (Group Low PEEP) and 10 cmH₂O PEEP (Group High PEEP). The PEEP was applied during general anesthesia, for controlled mechanical ventilation. The main outcome was the measurement of rSO2 before dura opening. Changes in rSO₂, hemodynamic parameters, and peripheral oxygen saturation (SpO₂) during different periods of surgery were compared between the groups. RESULTS Sixty-four patients were included. There were no significant differences between the 2 groups regarding demographic data. Mean arterial blood pressure and changes in SpO₂ were statistically similar in all periods between the groups (P=0.141 and P=0.081). When compared with the baseline value, SpO₂ increased significantly at all measurement times (P<
0.05). No difference was observed in rSO₂ values compared with baseline rSO₂ values between the groups (P=0.218). CONCLUSIONS PEEP at the level of 10 cmH₂O can be safely applied during craniotomy without altering hemodynamics, and without causing a decrease in rSO₂.