Intraoperative Liposomal Bupivacaine Injection in Primary Total Knee Arthroplasty

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain in primary total knee arthroplasty. The investigators hope to demonstrate equivalency of treatment modalities to provide an alternative to the commonly used treatment of femoral nerve blockade.

Detailed Description
-----------------
Postoperative pain control in total knee arthroplasty is generally managed by a multimodal approach of premedication, epidural and/or peripheral nerve blocks, narcotic medications, and anti-inflammatories. Multiple studies have evaluated the efficacy of anesthetic cocktails of various medications for local tissue infiltration to aide in controlling postoperative pain. A recent systematic review supported the use of local anesthetic infiltration in a single intraoperative dose as an adjunct to femoral nerve block in the relief of pain; with combinations of ropivacaine, ketorolac, and adrenaline providing the best results. Several studies noted decreases in opioid consumption and overall pain scores in the perioperative period. A novel compound, liposomal bupivacaine (EXPAREL®, Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA), has been proposed for use in total knee arthroplasty. To our knowledge, only one randomized controlled trial involving use of this compound in total knee arthroplasty has been published and was performed as a phase two dose ranging trial comparing liposomal bupivacaine to bupivacaine HCl. No statistically significant difference between the two compounds was shown, but a trend towards benefit in short term pain control was shown with EXPAREL 532mg. Our current pain management regimen utilizes the multimodal approach of neuraxial anesthesia, indwelling femoral nerve catheter, opioids, and anti-inflammatory medications. The regional anesthesia service manages postoperative pain while the indwelling femoral nerve catheter is in place. The epidural is utilized for early postoperative analgesia and thromboprophylaxis. The epidural is discontinued on post-operative day 1 and the femoral nerve catheter is removed by the morning of postoperative day 3. Although femoral nerve catheters provide excellent pain control following TKA, there are associated disadvantages. Most notably there is inherent quadriceps weakness which places the patient at increased fall risk. To reduce the risk of falling, patients must wear a knee immobilizer with ambulation until the catheter is removed and quadriceps function has returned. This may delay the ability to actively participate in physical therapy. The purpose of our present study is to evaluate the efficacy of local infiltration of liposomal bupivacaine versus use of an indwelling femoral peripheral nerve block in controlling early postoperative pain. The investigators aim to show equivalency between the two treatment modalities. Our hypothesis is that a systematic local infiltration of liposomal bupivacaine provided intraoperatively is equally efficacious as femoral indwelling peripheral nerve blockade in immediate postoperative pain control with more rapid progression with physical therapy.

Official Title
-----------------
Prospective Randomized Trial Comparing Intraoperative Liposomal Bupivacaine Injection With Indwelling Femoral Nerve Blockade in Early Postoperative Pain Control for Primary Total Knee Arthroplasty

Conditions
-----------------
Osteoarthritis, Osteoarthritis, Knee, Arthritis, Degenerative, Osteoarthrosis, Osteoarthrosis Deformans

Intervention / Treatment
-----------------
* Drug: Bupivacaine Liposome Injection
* Drug: Indwelling femoral nerve block


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age over 18 years old Undergoing unilateral primary total knee arthroplasty Exclusion Criteria: Revision total knee arthroplasty Bilateral total knee arthroplasty Prior allergy or adverse reaction to local anesthetic Hepatic dysfunction

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Femoral Nerve Blockade<br>Femoral nerve block delivered via indwelling femoral nerve catheter | Drug: Indwelling femoral nerve block<br>* Femoral nerve block delivered via indwelling femoral nerve catheter with 0.125% bupivacaine.<br>|
| Experimental: Bupivacaine Liposome Injection<br>Intraoperative intracapsular injection of bupivacaine liposome | Drug: Bupivacaine Liposome Injection<br>* Intraoperative intracapsular injection of 266mg of bupivacaine liposome injection diluted to 60mL with 0.9% normal saline.<br>* Other names: EXPAREL;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Pain Scale | 10cm VAS scale completed by the patient at set intervals postoperatively | 0-3 months | 
| Oral and Intravenous Opioid Consumption | Oral and intravenous opioid use calculated in terms of morphine equivalents | 0-5 days (during hospitalization) | 
| Hospital for Special Surgery (HSS) Knee Scores | Standardized functional clinical score for knee symptoms | 0-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospital Stay |  | 0-5 days | 
| Distance ambulated with physical therapy |  | 0-5 days (during hospitalization) | 
| Time to straight leg raise with physical therapy | Time to return of quadriceps function | 0-5 days (during hospitalization) | 
| Postoperative range of motion | Knee range of motion measure by physical therapy and in clinic | 0-3 months | 
| Postoperative complication rate | All intervention related complications for each arm of the study | 0-3 months | 
| Plasma bupivacaine concentrations | Plasma levels of bupivacaine monitored throughout hospital stay | 0-5 days (during hospitalization) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Total Knee Arthroplasty, Osteoarthritis, Femoral Nerve Blockade, Liposomal Bupivacaine