In total knee arthroplasty (TKA), the use of a tourniquet and controlled hypotension is common. However, ischemia-reperfusion injury induced by the tourniquet and inappropriate controlled hypotension can lead to cardiac and cerebral damage in patients. Consequently, maintaining hemodynamic stability, ensuring adequate cerebral perfusion, and achieving controlled blood pressure during the perioperative period are critical factors influencing patient outcomes. Postoperatively, patients typically experience moderate to severe pain. Severe postoperative pain can result in prolonged hospital stays, increased readmission rates, elevated opioid consumption, and associated nausea and vomiting. Therefore, exploring effective multimodal postoperative pain management strategies is essential. Nalbuphine, an opioid analgesic acting as a full kappa-receptor agonist and a partial mu-receptor antagonist, is considered to provide analgesic efficacy equivalent to morphine while potentially offering advantages in maintaining hemodynamic stability. This study aims to investigate the effects of administering equivalent doses of nalbuphine at different perioperative time points on analgesia and hemodynamics in elderly patients undergoing knee arthroplasty.

Total knee arthroplasty (TKA) is a widely performed routine surgical procedure for treating end-stage osteoarthritis (OA) or rheumatoid arthritis, aiming to alleviate pain and improve the quality of life for participants . However, participants undergoing TKA frequently experience moderate to severe postoperative pain during the perioperative period, with some even suffering from extremely severe pain . Intense postoperative pain can lead to prolonged hospital stays, increased readmission rates, elevated opioid consumption, and associated complications such as nausea and vomiting. These factors diminish participant satisfaction and escalate healthcare costs . Consequently, effective postoperative pain management is crucial for promoting early recovery and improving participant outcomes.

During TKA, periarticular tissue dissection and osteotomy cause bleeding and traumatic inflammation. Techniques such as tourniquet application and controlled hypotension are commonly employed. However, tourniquet-induced ischemia-reperfusion injury and inappropriate controlled hypotension can result in cardiac and cerebral injury for participants. Therefore, maintaining hemodynamic stability, ensuring adequate cerebral perfusion, and achieving controlled blood pressure throughout the perioperative period are critical factors for participant prognosis .

Opioids remain the conventional medication for perioperative pain relief. While effective for analgesia, they are associated with adverse effects such as respiratory depression, postoperative nausea and vomiting (PONV), and pruritus. Nalbuphine, an opioid acting as a full κ-receptor agonist and partial μ-receptor antagonist, is considered to provide analgesic efficacy equivalent to morphine and is widely used for managing moderate to severe postoperative pain . Studies indicate that nalbuphine offers superior hemodynamic stability and analgesic effects compared to morphine across various surgical procedures. It not only alleviates postoperative pain but also demonstrates a lower incidence of PONV. Its analgesic and sedative properties are also considered safe for use in pediatric populations . Nevertheless, conclusive evidence regarding the analgesic and hemodynamic effects of nalbuphine in elderly participants undergoing knee arthroplasty during the perioperative period remains lacking.

Therefore, this study aims to investigate the impact of administering equivalent doses of nalbuphine at different perioperative time points on analgesia and hemodynamics in elderly participants undergoing total knee arthroplasty.

Inclusion Criteria:

• All study participants voluntarily enrolled in the trial and provided written informed consent after being fully informed of the trial's purpose and significance
• Participants underwent unilateral total knee arthroplasty under general anesthesia
• Elderly participants (age ≥ 65 years), regardless of gender
• Body mass index (BMI) ranging from 18 kg/m² to 30 kg/m²
• Absence of psychiatric disorders, normal consciousness, and ability to communicate effectively
• American Society of Anesthesiologists (ASA) physical status classification I-III;
• No contraindications to the study medications

Exclusion Criteria:

• Study participants with uncontrolled or untreated hypertension (resting systolic/diastolic blood pressure >180/100 mmHg)
• Individuals with severe respiratory diseases
• Subjects with abnormal liver or renal function (ALT and/or AST >2.5 times the upper limit of normal, total bilirubin >1.5 times the upper limit of normal, serum creatinine >1.5 times the upper limit of normal)
• Individuals with a history of drug abuse, illicit drug use, or alcohol abuse, where alcohol abuse is defined as an average daily alcohol intake exceeding 2 units (1 unit = 360 mL of beer, 45 mL of 40% alcohol by volume spirits, or 150 mL of wine)