Analgesic Efficacy of Different Liposomal Bupivacaine Doses in the Adductor Canal Block for Total Knee Arthroplasty

Analgesic Efficacy of Different Liposomal Bupivacaine Doses in the Adductor Canal Block for Total Knee Arthroplasty: a Randomized Controlled Trial

Total knee arthroplasty is a commonly performed orthopaedic surgery for the treatment of end-stage osteoarthritis when conservative management becomes ineffective. TKA is associated with significant acute postoperative pain and many patients experience severe postoperative pain despite the use of multimodal analgesia. Poor acute postoperative pain control impacts rehabilitation, prolongs recovery and increases opioid consumption and chronic post-surgical pain.

Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals Inc, Parsippany, New Jersey, USA) is a multivesicular formulation of bupivacaine that prolongs drug release and can extend the duration of analgesia. The adductor canal block (ACB) has been shown to reduce pain intensity and opioid consumption after total knee arthroplasty. The use of liposomal bupivacaine in the adductor canal block has recently been FDA-approved. However, the results of its efficacy from existing clinical trials have been mixed. In addition, the doses in the clinical trials have been different, and the optimal dose for perineural application of liposomal bupivacaine is unclear, including for the adductor canal block.

In this project, the investigators propose to conduct a randomized controlled trial to investigate the effect of different doses of liposomal bupivacaine in the adductor canal block on acute postoperative pain intensity and opioid consumption after robotic assisted total knee arthroplasty. The investigators will also assess secondary outcomes including knee functional scores, chronic pain and quality of recovery.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Total Knee Arthroplasty; Analgesic Effect; Liposomal Bupivacaine; Dose Response Relationship, Drug
• Intervention / Treatment: Drug: 0.5% standard bupivacaine only; Drug: 1.33% liposomal bupivacaine with 0.5% standard bupivacaine; Drug: 1.33% liposomal bupivacaine only

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Stanley S.C. Wong, MD (HKU); Phone Number: (852) 2255 3303; Email: wongstan@hku.hk

Study Locations

• Hong Kong
  • Hong Kong
    • Hong Kong, Hong Kong, Hong Kong
      • Recruiting
      • The University of Hong Kong
      • Contact: Stanley S.C. Wong, MD (HKU); Phone Number: (852) 2255 3303; Email: wongstan@hku.hk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ASA I-III
• Age 18-80 years old
• Scheduled for elective primary unilateral total knee arthroplasty (TKA) with robotic surgery
• Able to speak and understand Cantonese or Mandarin or English
• Able to provide informed oral and written consent

Exclusion Criteria:

• Revision TKA
• Single-stage bilateral TKA
• Complex primary TKA requiring use of stem/augment/constrained liner
• Surgeries with significant intraoperative complications which may alter rehabilitation protocol eg collateral ligament injury, fracture requiring fixation
• Known allergy to opioids, local anaesthetic drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
• History of chronic pain other than chronic knee pain
• History of immunosuppression
• Chronic use of glucocorticoids
• Chronic opioid use (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
• History of congestive heart failure (NYHA 2)
• Alcohol or drug abuse
• Impaired renal function (defined as effective glomerular filtration rate < 30ml/min/1.73m2
• Impaired liver function (defined as plasma bilirubin over 34mol/L; international normalized ratio [INR] >= 1.7, alanine aminotransferase [ALT] over 100U/L, aspartate aminotransferase [AST] over 100U/L)
• Coagulopathy (platelet count <100,000/ml and/or INR >= 1.5) or the use of anticoagulants (not including aspirin) that precludes the use of adductor canal blocks
• Pre-existing neurological or muscular disorders
• Psychiatric illness
• Impaired mental state
• Pregnancy
• Local infection
• On immunosuppressants
• High body mass index (BMI) (>=40)
• Patient refusal for regional nerve blocks or to conduct clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACB using 20ml 0.5% standard bupivacaine (SB-ACB); adductor canal block with 20ml 0.5% standard bupivacaine only	Drug: 0.5% standard bupivacaine only; 20ml 0.5% standard bupivacaine only
Experimental: ACB using 10ml 1.33% liposomal bupivacaine with 10 ml 0.5% standard bupivacaine (LB10-ACB); adductor canal block with 10ml 1.33% liposomal bupivacaine (133mg) plus 10ml 0.5% standard bupivacaine	Drug: 1.33% liposomal bupivacaine with 0.5% standard bupivacaine; 10ml 1.33% liposomal bupivacaine (133mg) plus 10ml 0.5% standard bupivacaine
Experimental: ACB using 20ml 1.33% liposomal bupivacaine only (LB20-ACB); adductor canal block with 20ml 1.33% liposomal bupivacaine (266mg)	Drug: 1.33% liposomal bupivacaine only; 20ml 1.33% liposomal bupivacaine (266mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted area under curve (AUC) pain score	Pain severity would be rated at rest after surgery using numerical rating scale (NRS) with 0 to 10 where 0=no pain and 10=the worst possible pain	The first 48 hours after surgery when the patient is at rest

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS pain scores	NRS pain scores at rest and with movement (active knee flexion) from after surgery to postoperative day (POD) 7, ranging 0-10, with higher scores indicating more severe pain.	from after surgery to postoperative day 7
Oxynorm consumption	Oxynorm consumption from postoperative day (POD) 1-7	Postoperative day 1-7
Overall Benefit of Analgesic Score (OBAS)	Overall Benefit of Analgesic Score (OBAS) from postoperative day (POD) 1-7 (range, 0 [best] to 28 [worst])	Postoperative day (POD) 1-7
Quality of Recovery Questionnaire (QoR-9)	Quality of Recovery Questionnaire (QoR-9) on postoperative day 1, ranging from 0 to 18, with higher scores indicating good recovery after anaesthesia.	Postoperative day 1
Rehabilitation parameters (range of maximal active knee flexion)	Range of maximal active knee flexion will be assessed by the physiotherapists while the patient is in hospital.	While the patient is in hospital from postoperative day 0, day 1, and day 2.
Rehabilitation parameters (quadricep power)	Quadricep power will be assessed by the physiotherapists while the patient is in hospital. Ratings: 0 - no muscle contraction; - Move w/o gravity; - Raise then drop down immediately; - Raise against gravity w/o resistance; - Raise against gravity w/some resistance; - Raise against gravity w/ full resistance	While the patient is in hospital from postoperative day 0, day 1, and day 2.
Rehabilitation parameters (ability to perform straight leg raising)	Ability to perform straight leg raising will be assessed by the physiotherapists while the patient is in hospital. Ratings (Yes/ No).	While the patient is in hospital from postoperative day 0, day 1, and day 2.
Rehabilitation parameters (walking distance)	Walking distance (in metres) will be assessed by the physiotherapists while the patient is in hospital.	While the patient is in hospital from postoperative day 0, day 1, and day 2.
Rehabilitation parameters (Duration of hospital stay)	No. of hospitalization days from admission to discharge	estimated on average of postoperative day 7 at the date of discharge from hospital
Rehabilitation parameters (discharge location)	Home or rehabilitation center	estimated on average of postoperative day 7 at the date of discharge from hospital
Opioid-related side effects	Presence or absence of pruritus, dizziness, nausea, and vomiting will be recorded.	While the patient is in hospital from postoperative day 0, 1, and 2.
Potential side effects related to adductor canal block (ACB)	Presence or absence of local anaesthetic toxicity, neurological injury, and intravascular injection will be recorded.	While the patient is in hospital from postoperative day 0, 1, and 2.
Analgesic block duration	Measured in time to return of pain (When did your pain relief from the block completely wear off?), time to sensory resolution (When did your numbness completely resolve and return to normal?), and time to motor resolution (When did your arm or hand weakness resolve and return to normal?)	While the patient is in hospital at postoperative day 1
Sensory and motor assessment	The affected lower limb will be measured. Sensory assessment (Sensation to pin prick), rating from 0 (no sensation) to 10 (normal sensation) Motor assessment; Straight leg raising achieved Ratings (Yes/ No); Quadriceps power Ratings: 0 - no muscle contraction; - Move w/o gravity; - Raise then drop down immediately; - Raise against gravity w/o resistance; - Raise against gravity w/some resistance; - Raise against gravity w/ full resistance	While the patient is in hospital from post-block 2 hours, 6 hours, 12 hours, and 24 hours.
quality of life (SF12v2)	Eight domains of SF-12v2 (HK) are measured on a scale ranging from 0 to 100. A higher domain score indicates a better HRQoL.	at 6 weeks and at 3 and 6 months after surgery
Identification Pain Questionnaire for Neuropathic Pain (ID-NeP)	Neuropathic pain will be assessed using Identification Pain Questionnaire for Neuropathic Pain (ID-NeP), consisting of six items: "Yes" answers to questions 1-5 were given a score of 1, while "yes" answer to question 6 scored -1. "No" answers to questions 1-5 were given a score of 0, while "yes" answer to question 6 scored 0.	at 6 weeks, 3 months and 6 months postoperatively
Knee Society Knee Function Score	Knee Society Knee Function Score at 6 weeks, 3 months and 6 months postoperatively, from 0 to 100 with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions.	at 6 weeks, 3 months and 6 months postoperatively
Chronic post-surgical pain	The presence or absence of chronic post-surgical pain, pain scores if present.	at 6 weeks, 3 months and 6 months postoperatively
Plasma level of bupivacaine and ropivacaine	Plasma level of bupivacaine and ropivacaine before and after surgery	Blood will be collected during induction, at 12 hours, 24 hours, 48 hours, and 72 hours after ACB.

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Publications and helpful links

General Publications

• Jiang X, Wang QQ, Wu CA, Tian W. Analgesic Efficacy of Adductor Canal Block in Total Knee Arthroplasty: A Meta-analysis and Systematic Review. Orthop Surg. 2016 Aug;8(3):294-300. doi: 10.1111/os.12268.
• Lam ET, Lam CL, Fong DY, Huang WW. Is the SF-12 version 2 Health Survey a valid and equivalent substitute for the SF-36 version 2 Health Survey for the Chinese? J Eval Clin Pract. 2013 Feb;19(1):200-8. doi: 10.1111/j.1365-2753.2011.01800.x. Epub 2011 Nov 29.
• Rawal N. Current issues in postoperative pain management. Eur J Anaesthesiol. 2016 Mar;33(3):160-71. doi: 10.1097/EJA.0000000000000366.
• Lavand'homme PM, Kehlet H, Rawal N, Joshi GP; PROSPECT Working Group of the European Society of Regional Anaesthesia and Pain Therapy (ESRA). Pain management after total knee arthroplasty: PROcedure SPEcific Postoperative Pain ManagemenT recommendations. Eur J Anaesthesiol. 2022 Sep 1;39(9):743-757. doi: 10.1097/EJA.0000000000001691. Epub 2022 Jul 20.
• Culliton SE, Bryant DM, MacDonald SJ, Hibbert KM, Chesworth BM. Validity and Internal Consistency of the New Knee Society Knee Scoring System. Clin Orthop Relat Res. 2018 Jan;476(1):77-84. doi: 10.1007/s11999.0000000000000014.
• Portenoy R. Development and testing of a neuropathic pain screening questionnaire: ID Pain. Curr Med Res Opin. 2006 Aug;22(8):1555-65. doi: 10.1185/030079906X115702.
• Chan MT, Lo CC, Lok CK, Chan TW, Choi KC, Gin T. Psychometric testing of the Chinese quality of recovery score. Anesth Analg. 2008 Oct;107(4):1189-95. doi: 10.1213/ane.0b013e318184b94e.
• Lehmann N, Joshi GP, Dirkmann D, Weiss M, Gulur P, Peters J, Eikermann M. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument. Br J Anaesth. 2010 Oct;105(4):511-8. doi: 10.1093/bja/aeq186. Epub 2010 Aug 6.
• Cohen, J., Statistical power analysis for the behavioral sciences. 2013: routledge.
• Quaye A, McAllister B, Garcia JR, Nohr O, Laduzenski SJ, Mack L, Kerr CR, Kerr DA, Razafindralay CN, Richard JM, Craig WY, Rodrigue S. A prospective, randomized trial of liposomal bupivacaine compared to conventional bupivacaine on pain control and postoperative opioid use in adults receiving adductor canal blocks for total knee arthroplasty. Arthroplasty. 2024 Feb 1;6(1):6. doi: 10.1186/s42836-023-00226-y.
• Malige A, Pellegrino AN, Kunkle K, Konopitski AK, Brogle PJ, Nwachuku CO. Liposomal Bupivacaine in Adductor Canal Blocks Before Total Knee Arthroplasty Leads to Improved Postoperative Outcomes: A Randomized Controlled Trial. J Arthroplasty. 2022 Aug;37(8):1549-1556. doi: 10.1016/j.arth.2022.03.073. Epub 2022 Mar 26.
• Hungerford M, Neubauer P, Ciotola J, Littleton K, Boner A, Chang L. Liposomal Bupivacaine vs Ropivacaine for Adductor Canal Blocks in Total Knee Arthroplasty: A Prospective Randomized Trial. J Arthroplasty. 2021 Dec;36(12):3915-3921. doi: 10.1016/j.arth.2021.08.017. Epub 2021 Aug 21.
• Hubler CP, Bevil KM, Greiner JJ, Hetzel SJ, Borden SB, Cios HA. Liposomal Bupivacaine Versus Standard Bupivacaine in the Adductor Canal for Total Knee Arthroplasty: A Randomized, Controlled Trial. Orthopedics. 2021 Jul-Aug;44(4):249-255. doi: 10.3928/01477447-20210621-01. Epub 2021 Jul 1.
• Lv J, Huang C, Wang Z, Ou S. Adductor canal block combined with local infiltration analgesia versus isolated adductor canal block in reducing pain and opioid consumption after total knee arthroplasty: a systematic review and meta-analysis. J Int Med Res. 2020 Aug;48(8):300060520926075. doi: 10.1177/0300060520926075.
• Li Y, Li A, Zhang Y. The efficacy of combined adductor canal block with local infiltration analgesia for pain control after total knee arthroplasty: A meta-analysis. Medicine (Baltimore). 2018 Dec;97(49):e13326. doi: 10.1097/MD.0000000000013326.
• Zuo W, Guo W, Ma J, Cui W. Dose adductor canal block combined with local infiltration analgesia has a synergistic effect than adductor canal block alone in total knee arthroplasty: a meta-analysis and systematic review. J Orthop Surg Res. 2019 Apr 11;14(1):101. doi: 10.1186/s13018-019-1138-5.
• Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021 Feb 1;134(2):283-344. doi: 10.1097/ALN.0000000000003630.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: November 29, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: total knee arthroplasty; opioid consumption; liposomal bupivacaine; local infiltration analgesia; adductor canal block
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Bupivacaine
• Other Study ID Numbers: UW24-691

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No