Dexamethasone vs Dexmedetomidine for iPACK + ACB in TKA

Perineural Dexamethasone Versus Perineural Dexmedetomidine as Adjuvants to Ropivacaine in iPACK and Adductor Canal Blocks for Total Knee Arthroplasty: A Randomized, Double-Blind, Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Ropivacaine 0.2% Injectable Solution; Drug: Dexamethasone 4mg; Drug: Dexmedetomidine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Malgorzata Reysner, MD PhD; Phone Number: +48 61 873 83 03; Email: mreysner@ump.edu.pl

Study Locations

• Poland
  • Poznan, Poland, 62-701
    • Recruiting
    • Poznan University of Medical Sciences
    • Contact: Malgorzata Reysner, M.D. Ph.D.; Phone Number: +48 61 873 83 03; Email: mreysner@ump.edu.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 65 years
• Scheduled for primary unilateral total knee arthroplasty under standardized anesthetic protocol
• ASA physical status II-III (or I-III, zależnie jak planujesz)
• Ability to understand the study procedures and provide written informed consent

Exclusion Criteria:

• Contraindications to peripheral nerve blocks (infection at injection site, coagulopathy, patient refusal)
• Known allergy or hypersensitivity to amide local anesthetics, dexamethasone or dexmedetomidine
• Chronic opioid therapy or opioid use > 30 mg oral morphine equivalents per day in the last 3 months
• Severe hepatic or renal impairment
• Significant cognitive impairment, inability to cooperate with pain assessment
• Participation in another interventional trial affecting pain or analgesic consumption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Patients receive ultrasound-guided iPACK block and adductor canal block (ACB) on the operative limb with ropivacaine 0.2% alone, without any perineural adjuvant.	Drug: Ropivacaine 0.2% Injectable Solution; Ultrasound-guided iPACK block and adductor canal block are performed using ropivacaine 0.2% in a standardized volume per block (20 mL for iPACK and 20 mL for ACB; adjust according to protocol). No adjuvant is added to the local anesthetic solution.
Experimental: Perineural Dexamethasone; Patients receive ultrasound-guided iPACK and ACB with ropivacaine 0.2% combined with perineural dexamethasone.	Drug: Dexamethasone 4mg; Ultrasound-guided iPACK block and adductor canal block are performed using ropivacaine 0.2% in a standardized volume per block (20 mL + 20 mL). Preservative-free dexamethasone is added to the local anesthetic solution at a dose of (2 x 2 mg).
Experimental: Perineural Dexmedetomidine; Patients receive ultrasound-guided iPACK and ACB with ropivacaine 0.2% combined with perineural dexmedetomidine.	Drug: Dexmedetomidine; Ultrasound-guided iPACK block and adductor canal block are performed using ropivacaine 0.2% in a standardized volume per block (20 mL + 20 mL). Dexmedetomidine is added to the local anesthetic solution at a dose of 25ug, distributed between both blocks according to the study protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative opioid consumption in the first 24 hours after surgery	Total dose of rescue opioid analgesics administered within the first 24 hours after surgery, converted to intravenous morphine equivalents (mg). All opioids given in the post-anesthesia care unit and on the ward will be recorded and converted using standard equianalgesic ratios.	0-24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity at rest	Pain intensity at rest assessed using an 11-point Numeric Rating Scale (NRS, 0 = no pain, 10 = worst imaginable pain)	6 hours postoperatively
Pain intensity at rest	Pain intensity at rest assessed using an 11-point Numeric Rating Scale (NRS, 0 = no pain, 10 = worst imaginable pain)	12 hours postoperatively
Pain intensity at rest	Pain intensity at rest assessed using an 11-point Numeric Rating Scale (NRS, 0 = no pain, 10 = worst imaginable pain)	24 hours postoperatively
Pain intensity at rest	Pain intensity at rest assessed using an 11-point Numeric Rating Scale (NRS, 0 = no pain, 10 = worst imaginable pain)	48 hours postoperatively
Pain intensity during mobilization	Pain during active knee flexion and mobilization (e.g., physiotherapy session) assessed using NRS (0-10)	24 hours postoperatively
Pain intensity during mobilization	Pain during active knee flexion and mobilization (e.g., physiotherapy session) assessed using NRS (0-10)	48 hours postoperatively
Time to first rescue analgesia	Time from completion of the iPACK and ACB blocks to the administration of the first dose of rescue opioid analgesic (in minutes).	0-48 hours postoperatively
Incidence of postoperative nausea and vomiting (PONV)	Number of patients with at least one episode of nausea and/or vomiting requiring antiemetic treatment during the first 24 and 48 hours after surgery.	0-48 hours postoperatively
Motor function of the operated limb	Quadriceps muscle strength (knee extension and hip adduction) assessed using the Medical Research Council (MRC) scale, ranging from 0 (no muscular contraction) to 5 (normal strength), to evaluate the motor-sparing profile of each analgesic regimen.	6 hours postoperatively
Motor function of the operated limb	Quadriceps muscle strength (knee extension and hip adduction) assessed using the Medical Research Council (MRC) scale, ranging from 0 (no muscular contraction) to 5 (normal strength), to evaluate the motor-sparing profile of each analgesic regimen.	12 hours postoperatively
Motor function of the operated limb	Quadriceps muscle strength (knee extension and hip adduction) assessed using the Medical Research Council (MRC) scale, ranging from 0 (no muscular contraction) to 5 (normal strength), to evaluate the motor-sparing profile of each analgesic regimen.	24 hours postoperatively
Block-related and systemic adverse events	Incidence of bradycardia, hypotension, oversedation, local anesthetic systemic toxicity (LAST), neurological deficits, signs of infection at the injection site, or any serious adverse events possibly related to the study drugs or blocks.	Intraoperative and up to 48 hours postoperatively

Collaborators and Investigators

• Sponsor: Poznan University of Medical Sciences
• Investigators: Study Chair: Malgorzata Reysner, MD PhD, Poznan University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: January 29, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Imidazoles; Anilides; Amides; Aniline Compounds; Amines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Ropivacaine; Dexamethasone; Dexmedetomidine
• Other Study ID Numbers: 13/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie the results reported in the published article will be made available after de-identification. Data will include demographic characteristics, perioperative variables, intervention details, and primary and secondary outcomes.
• IPD Sharing Time Frame: The data will be available beginning 6 months after publication of the main results and for a period of at least 5 years.
• IPD Sharing Access Criteria: Data will be shared with qualified researchers for legitimate scientific purposes upon reasonable request. Access requires submission of a methodologically sound proposal, approval by the study investigators, and a data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No