Effectiveness of Adductor Canal Block Using Liposomal Bupivacaine

Comparing the Efficacy of Combining Periarticular Local Infiltration of Analgesia and Adductor Canal Block Using Liposomal Bupivacaine and Standard Bupivacaine in Total Knee Arthroplasty - A Prospective Randomized Controlled Trial

With aging of population, osteoarthritis of knees and hips become major orthopaedic problems in Hong Kong. Osteoarthritis of knees and hips are associated with significant pain problem and functional disability. Total joints replacement is the ultimate surgical procedures to deal with such problems.

However total joints replacement is associated with significant tissue damage and post-operative pain problems, which would affect post-operative recovery and rehabilitation.

The primary aims of total knee replacement are improvement in functional activities and reduce pain due to degenerated knee joints. However, there are around 20-30% of patients would develop significant pain problem despite uncomplicated total knee replacement. It accounts for major post-operative problems and burdens.

Procedure specific analgesic method with multi-model analgesia technique is well-known to be useful in post-operative pain management, which reduces the post-operative pain score. However, despite using of multi-modal analgesic technique, pain after total joint replacement is still the most unsolved issue. It prolongs the recovery period and increases post-operative analgesic consumptions.

Multimodal analgesia, including periarticular local infiltration of analgesia (LIA), regional nerve block, opioid and non-opioid have been shown to be effective in managing postoperative pain.

Periarticular LIA has been shown to be an effective way of pain management. Regional nerve block using femoral nerve block or adductor canal block (ACB) is also a well-established anlagesic technique after total knee replacement. Comparing with femoral nerve block, it involves more sensory blockade so has the advantage of quadriceps sparing, less affecting the post-operative mobilization.

From most recent systematic reviews and randomized controlled trials, it becomes clear that periarticular LIA has better pain control with less opioid consumption than ACB alone. However, duration of a single-dose LIA may not be long enough after total knee replacement. Recent meta-analysis has shown that combined ACB with LIA could significantly reduce pain scores and morphine consumption compared LIA alone after TKA. Standard bupivacaine, levobupivocaine, ropivocaine were used in ACB in these studies. They are local anaesthetic with half-life ranging from 3-6 hours.

With the availability of liposomal bupivacaine (LB), ACB using LB may further prolong the analgesic effect of ACB as the therapeutic levels of bupivacaine, which are below the toxic range and sustained for 72 hours after injection. Therefore, the issue is whether ACB using LB has even longer analgesic effect than plain bupivacaine or ropivacaine. There was only one study directly compared ACB using LB and 0.1% ropivociane infusion. It was shown that LB had significant impact in pain control in the first 36 hours. However, this was a retrospective study and there was difference in delivery of local anaesthetics (single shot injection for liposomal bupivacaine but continuous infusion for ropivacaine).

The primary aim of this study is to investigate whether ACB using liposomal bupivacaine has even longer analgesic effect than standard bupivacaine (SB) and its cost effectiveness. Secondary aims are to evaluate the pharmacokinetic data of standard bupivacaine and liposomal bupivacaine in adductor canal block and pharmacokinetic data of ropivocaine level in LIA.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: Bupivacaine Injection

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chi Wing Chan, MBBS; Phone Number: 2255 5791; Email: timmychancw@gmail.com

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
    • Contact: Chi Wing Chan, MBBS; Phone Number: 2255 5791; Email: timmychancw@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (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 replacement
• Chinese patients
• BMI < 40
• Able to speak and understand Cantonese
• Able to provide informed oral and written consent

Exclusion Criteria:

• Revision total knee replacement
• Single stage bilateral total knee replacement
• 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
• Daily use of glucocorticoids
• Daily use of strong opioids (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
• History of severe heart disease (NYHA 2)
• Alcohol or drug abuse
• Impaired renal function, defined as preoperative serum creatinine level over 120 μmol/L
• Pre-existing neurological or muscular disorders
• Psychiatric illness or neurologic or psychiatric diseases potentially influencing pain perception
• Impaired or retarded mental state
• Difficulties in using patient controlled analgesia (PCA)
• Pregnancy
• Local infection
• On immunosuppresants
• Patient refusal

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group LB; local infiltration of analgesia (LIA) with adductor canal block (ACB) will be given using 10ml of 1.33% liposomal bupivacaine with 10ml 0.5% standard bupivacaine	Drug: Liposomal bupivacaine; LIA with ACB will be given using 10ml of 1.33% liposomal bupivacaine + 10ml 0.5% standard bupivacaine
Active Comparator: group SB; LIA with ACB will be given using 20ml 0.5%standard bupivacaine	Drug: Bupivacaine Injection; LIA with ACB will be given using 20ml 0.5% standard bupivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain assessed by numerical rating scales (NRS) pain scores	NRS pain scores (from 0-10, where 0 is the least satisfaction and 10 most satisfaction) will be recorded during movement and at rest, by NRS (movement) and NRS (rest) respectively	at postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Range of motion (ROM) of knee	Active and Passive ROM of knee (flexion and extension) will be recorded.	from postoperative day 0 until postoperative day 6
Walking Distance	Walking distance will be measured in meters	from postoperative day 0 until postoperative day 6
Degree of assistance	Patients' ability to walk will be assessed. There are three categories including walking without help, walking with walking frame and being unable to walk	from postoperative day 0 until postoperative day 6
Ability to preform straight leg raising	Patients' ability to preform straight leg raising is recorded after surgery	from postoperative day 0 until postoperative day 6
Plasma level of bupivacaine and ropivacaine.	Blood sample would be collected and plasma level of bupivacaine and ropivacaine would be measured using liquid chromatography coupled mass spectrometry.	at before ACB, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours, and 72 hours after ACB.

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Chi Wing Chan, MBBS, Queen Mary Hospital, Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: total knee replacement; anaesthesia; post operative pain; acute pain; bupivacaine; LIA; ACB
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: UW19-304

Drug and device information, study documents

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