Dexamethasone vs Dexmedetomidine for iPACK + ACB in TKA

Overview

This randomized, double-blind, controlled trial is designed to compare the analgesic efficacy and safety of perineural dexamethasone versus perineural dexmedetomidine as adjuvants to ropivacaine for ultrasound-guided interspace between the popliteal artery and the capsule of the posterior knee (iPACK) and adductor canal blocks in patients undergoing primary unilateral total knee arthroplasty (TKA). Elderly participants scheduled for elective TKA will be randomized into three parallel groups: ropivacaine alone (control), ropivacaine combined with perineural dexamethasone, or ropivacaine combined with perineural dexmedetomidine. The primary objective is to determine whether the addition of either adjuvant reduces postoperative opioid consumption compared with ropivacaine alone and to assess potential differences in analgesic efficacy between the two adjuvants. Secondary outcomes include pain intensity at rest and during mobilization, time to first rescue analgesia, quality of early functional recovery, and the incidence of adverse events, including postoperative nausea and vomiting, motor impairment, and hemodynamic instability.

Total knee arthroplasty (TKA) is associated with substantial postoperative pain, which may delay rehabilitation, prolong hospital stay, and increase opioid consumption. Ultrasound-guided peripheral nerve blocks are an integral component of multimodal analgesia for TKA, particularly the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) block and the adductor canal block (ACB). These techniques provide effective analgesia while preserving quadriceps motor function, thereby facilitating early mobilization. Ropivacaine is the most commonly used local anesthetic for iPACK and ACB; however, its relatively limited duration often necessitates additional analgesic interventions. Perineural adjuvants have attracted increasing interest as a means to prolong block duration and enhance the quality of peripheral nerve blockade. Dexamethasone and dexmedetomidine are among the most extensively studied adjuvants; however, their relative clinical efficacy and safety when administered perineurally in TKA remain uncertain. Dexamethasone has been shown to prolong block duration and reduce postoperative pain and opioid requirements, likely through anti-inflammatory and glucocorticoid-mediated mechanisms. Dexmedetomidine, an α2-adrenergic agonist, may further enhance analgesia and sensory block duration but has been associated with adverse effects such as sedation and bradycardia in susceptible patients. Comparative evidence between these agents in the specific context of combined iPACK and ACB is limited, and no clear consensus currently exists regarding their optimal use. This randomized, double-blind, controlled clinical trial is designed to compare the efficacy and safety of perineural dexamethasone versus perineural dexmedetomidine as adjuvants to ropivacaine for ultrasound-guided iPACK and adductor canal blocks in elderly patients undergoing primary unilateral total knee arthroplasty. Eligible participants will be randomized into three parallel groups: ropivacaine alone (control), ropivacaine with perineural dexamethasone, or ropivacaine with perineural dexmedetomidine. All nerve blocks will be performed according to a standardized protocol by experienced anesthesiologists. Surgical, anesthetic, and postoperative analgesic management will be standardized across groups to minimize potential confounding factors. Participants, care providers, investigators, block practitioners, nursing staff, and outcome assessors will remain blinded to treatment allocation. The primary outcome is cumulative opioid consumption during the first 24 postoperative hours, expressed as intravenous morphine equivalents. Secondary outcomes include pain intensity at rest and during mobilization, time to first rescue analgesia, motor-sparing profile, hemodynamic effects, quality of early recovery, and the incidence of adverse events such as postoperative nausea and vomiting, hypotension, bradycardia, and neurological symptoms. Functional recovery will additionally be evaluated using standardized physiotherapy milestones. It is hypothesized that both perineural dexamethasone and dexmedetomidine will reduce postoperative opioid consumption compared with ropivacaine alone, and that one adjuvant may demonstrate superior analgesic efficacy or a more favorable safety profile. The findings of this study may provide clinically relevant evidence to guide the selection of perineural adjuvants for iPACK and adductor canal blocks in total knee arthroplasty, with the potential to improve pain control, accelerate rehabilitation, and reduce opioid exposure in an elderly, at-risk population.