Two hundred twenty-eight elderly patients undergoing unilateral total knee arthroplasty were randomized to receive either NOX-guided intraoperative analgesia (n=114) or routine monitoring based on BIS alone (n=114). The primary outcome was the incidence of postoperative delirium (POD) within 3 days post-surgery, assessed by the Confusion Assessment Method. Secondary outcomes included VAS pain scores at 24, 48, and 72 hours, anesthetic drug dosages, length of hospital stay, analgesic pump usage, and intraoperative BIS and NOX values. Outcomes were assessed during the first 3 postoperative days. Overall, the results revealed a significantly lower POD incidence on postoperative day 1 in the NOX group (7%) compared to the routine group, though no significant differences were found on subsequent days. The study concludes that intraoperative analgesia guided by NOX significantly reduces early POD, suggesting a key role of pain control in improving cognitive outcomes after surgery.