Observation Study of the Pharmacokinetics of Adductor Canal Block

An Observational Study of the Pharmacokinetics of Adductor Canal Block Using Liposomal Bupivacaine and Standard Bupivacaine in Total Knee Arthroplasty Patients

With the aging of the population, osteoarthritis of knees and hips become major orthopedic problems worldwide. Osteoarthritis of the knees and hips is associated with a significant pain problem and functional disability. Total joints replacement is the ultimate surgical procedure to deal with such problems. Multimodal analgesia, including periarticular local infiltration of analgesia (LIA), regional nerve block using adductor canal block (ACB), opioid and non-opioid have been shown to be effective in managing postoperative pain. Regional nerve block using femoral nerve block or adductor canal block (ACB) is also a well-established analgesic technique after total knee replacement. Standard bupivacaine (SB), levobupivacaine, ropivacaine were used in ACB in these studies. Whether combining ACB with periarticular LIA has the additional benefit of prolonging analgesia or with synergistic effect remains controversial, because the number of RCTs conducted is not enough. Liposomal bupivacaine (LB) may further prolong the analgesic effect of ACB, as the therapeutic levels of bupivacaine are below the toxic range and sustained for 72 hours after injection. The purpose of this study is to evaluate the safety and systemic levels of serum bupivacaine following adductor canal block using LB 66.5mg in patients undergoing TKA with LIA over a 72-hour period. This also serves as a pilot study to determine the dose and timing of blood taking for serum bupivacaine level of a previously IRB approved study - "Comparing the efficacy of combining periarticular local infiltration of analgesia and adductor canal block using liposomal bupivacaine and standard bupivacaine- A prospective randomized controlled trial".

Study Overview

• Status: Completed
• Conditions: Toxicity, Drug
• Intervention / Treatment: Drug: Liposomal bupivacaine

Detailed Description

After signing the consent form, participants will receive LIA with ACB using 5ml of 1.33% liposomal bupivacaine with 5ml of 0.9% normal saline.

Participants will receive routine preoperative, intraoperative, and postoperative treatments like other patients undergoing total knee replacement.

Blood will be collected during induction, at 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours after the performance of ACB through a designated 14-gauge cannula, and also at 24, 48, and 72 hours after the operation during routine blood taking.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients admitted for elective primary unilateral total knee replacement in Queen Mary Hospital.

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:

• Single-stage bilateral total knee replacement
• Complex primary total knee replacement requiring the use of stem/augment/constrained liner
• Surgeries with significant intraoperative complications which may alter rehabilitation protocol e.g. 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
• 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 micromol/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 immunosuppressants
• High BMI (>=40)
• Patient refusal

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
liposomal bupivacaine; Nerve block will be preformed using 5ml of 1.33% liposomal bupivacaine with 5ml of 0.9% normal saline.	Drug: Liposomal bupivacaine; 5ml of 1.33% liposomal bupivacaine with 5 ml of 0.9% normal saline will be given to treatment group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak concentration of serum bupivacaine	Serum bupivacaine will be quantified using High Performance Liquid Chromatography.	72 hours after the operation

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 7, 2021

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

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: UW20-589

Drug and device information, study documents

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