This prospective, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of intraoperative ketamine and dexmedetomidine on the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing total joint arthroplasty. Given the high incidence of neurocognitive complications in elderly patients following major orthopedic surgeries, neuroprotective strategies during anesthesia are of growing interest. Both ketamine and dexmedetomidine have shown potential in reducing neuroinflammation and improving postoperative cognitive outcomes in previous studies.

Eighty adult patients (ASA I-III, aged 18-100) scheduled for elective total hip or knee arthroplasty under spinal anesthesia will be randomized into four groups: control (saline infusion), ketamine infusion, dexmedetomidine infusion, and combined ketamine + dexmedetomidine. Cognitive assessments will be performed preoperatively and on postoperative days 2 and 15 using the Mini Mental State Examination (MMSE). Delirium assessments will be conducted using the Confusion Assessment Method (CAM) postoperatively on days 1, 3, and 15.

Secondary outcomes include perioperative levels of cortisol, CRP, and fibrinogen, as well as postoperative pain scores (VAS) and analgesic consumption. The results are expected to clarify whether intraoperative administration of ketamine or dexmedetomidine can reduce the incidence of POD/POCD and improve postoperative recovery.

Inclusion Criteria:

• Scheduled for elective total joint arthroplasty (hip or knee)
• ASA physical status I-III
• Age between 18 and 100 years
• Ability to provide informed consent and comply with cognitive assessments

Exclusion Criteria:

• Pre-existing cognitive dysfunction or diagnosed neurodegenerative disease
• Hearing or language impairment interfering with MMSE/CAM evaluation
• Known allergy to ketamine or dexmedetomidine
• Significant cardiac arrhythmia (e.g., supraventricular tachycardia, 2nd or 3rd degree AV block)
• Renal insufficiency (GFR <30 mL/min/1.73 m²)
• Severe hepatic dysfunction