Effective postoperative pain management remains a cornerstone of enhanced recovery protocols following total knee arthroplasty (TKA). Inadequate analgesia not only compromises patient satisfaction but also impedes early mobilization and rehabilitation, thereby increasing the risk of perioperative complications. Current multimodal analgesic strategies frequently incorporate regional techniques, with the adductor canal block (ACB) and infiltration between the popliteal artery and capsule of the knee (IPACK) block emerging as established modalities that provide motor-sparing analgesia.

Despite their widespread adoption, the optimal local anesthetic regimen for these blocks remains undefined. While liposomal bupivacaine has garnered interest for its extended duration of action, its clinical efficacy relative to conventional local anesthetics combined with perineural adjuncts remains a subject of ongoing debate. Specifically, perineural dexamethasone and dexmedetomidine have each demonstrated the capacity to prolong the analgesic duration of ropivacaine; however, direct comparative data among these three distinct strategies-liposomal bupivacaine alone versus ropivacaine supplemented with either adjunct-are notably limited.

Given the absence of head-to-head randomized trials evaluating these three clinically viable techniques, the optimal approach to maximize analgesic duration while minimizing opioid-related adverse effects remains unclear. This study therefore aims to compare the analgesic efficacy and safety profiles of liposomal bupivacaine, ropivacaine with perineural dexamethasone, and ropivacaine with perineural dexmedetomidine when administered via ACB and IPACK blocks in patients undergoing TKA.

Inclusion Criteria:

• Patients scheduled for elective primary unilateral total knee arthroplasty
• Age ≥ 18 years and ≤ 80 years
• American Society of Anesthesiologists (ASA) physical status I-III
• Body mass index (BMI) ≥ 18 kg/m² and ≤ 35 kg/m²
• Ability to understand and provide written informed consent

Exclusion Criteria:

• Known allergy or contraindication to local anesthetics (bupivacaine, ropivacaine), dexamethasone, dexmedetomidine, or opioids
• Infection at the injection site
• Coagulopathy or current use of anticoagulants
• Severe cardiovascular disease (New York Heart Association [NYHA] functional class III or IV, or recent myocardial infarction within 6 months)
• Severe hepatic impairment (Child-Pugh class C) or renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg despite medical therapy)
• Uncontrolled diabetes mellitus (HbA1c > 8.5%)
• Bilateral TKA or revision TKA
• Chronic opioid use (daily opioid consumption for > 3 months prior to surgery)
• Participation in another interventional clinical trial within 30 days prior to enrollment
• Inability to communicate with study personnel or complete pain assessments (e.g., language barrier, cognitive impairment)

Data sharing is not permitted due to restrictions in the informed consent form and institutional policy. Participants did not provide consent for sharing their data beyond the primary study. Additionally, the Institutional Review Board has not approved a data sharing plan for this trial.