Intraoperative Liposomal Bupivacaine vs. Bupivacaine for Total Hip Replacement Pain Management

Post-surgical Pain Care Pathways During Enhanced Recovery Surgery Using Exparel (Bupivacaine Liposome Injectable Suspension) Plus Bupivacaine With Epinephrine Versus Bupivacaine.

The purpose of this study is to compare two medications currently injected intra-operatively to help decrease pain after surgery in patients undergoing a primary total hip replacement (THR). The two medications are Exparel® (bupivacaine liposome injectable suspension) plus bupivacaine with epinephrine versus bupivacaine with epinephrine. This study is looking to see if one medication works better than the other in managing post-operative pain after THR. The study hypothesis is that Exparel® plus bupivacaine with epinephrine will demonstrate better pain management in THR patients post-operatively. Both medications are FDA-approved for post-operative analgesia.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Liposomal Bupivacaine; Drug: 0.25% Bupivacaine with epinephrine; Drug: Saline

Detailed Description

All surgeries were performed by the same orthopaedic surgeon. Two groups, one receiving Exparel® (bupivacaine liposome injectable suspension) plus bupivacaine with epinephrine (LB group) and the other receiving bupivacaine with epinephrine (Control group), will be compared using post-operative pain scores, hospital length of stay, time to ambulation, falls, narcotic use, and narcotic-related adverse effects. Aside from hospital length of stay, all outcomes were recorded for up to 72 hours following surgery. An a priori power analysis was performed to calculate the total number of patients that needed to be enrolled to achieve a minimum 90% power, with the threshold of statistical significance set to 0.05. Based on a previous study reporting a mean oral opioid consumption of 57.04mg ± 25.6 at 24 hours post THR, a mean difference of 17.14mg was considered to be clinically significant. Thus, at least 26 patients were necessary in each group for an adequately powered assessment. The diagnosis for osteoarthritis was determined by patient history, physical examination, and imaging findings. Each patient received a thorough explanation of the protocol, and willing patients signed an informed consent form. All patients underwent a personal preoperative education program regarding pre, intra-, and post-procedural information including physical therapy, expectations, discharge goals, home therapy, and pain management. After written consent was collected, the form was sent to the hospital pharmacy for randomization. Envelopes were randomized, sealed, numbered, and given to the pharmacy staff, ultimately dispensing the envelopes to the nurse in the operating room in numerical order. The pharmacy documented the required information, selected medication, and drug accountability forms according to the contents of the envelopes.

A nurse delivered study drugs to the operating room in a sealed, non-descriptive envelope. During the standard anterior approach procedure, an anesthesiologist administered fentanyl or hydromorphone as needed for analgesia. The local anesthetics were administered after reduction of the implants. Patients in the LB group received 20cc liposomal bupivacaine, 40cc 0.25% bupivacaine with epinephrine, and 20cc of normal saline. Each patient in the control group received 60cc of 0.25% bupivacaine with epinephrine. Using a 20-gauge spinal needle, the local anesthetics were injected using a deep tissue administration technique. Structures innervated by the femoral nerve, superior gluteal nerve, or lateral femoral cutaneous nerve were considered suitable for injection. Throughout administration, frequent aspirations were performed to check for blood and minimize the risk of intravascular injection. The patients, surgical team, and floor staff was blinded to the local anesthetic drugs given.

During hospitalization, patients were observed, evaluated and treated according to postoperative protocols. Patients received opioids for pain management as needed, which was routinely documented by hospital staff. Opioids included fentanyl, hydromorphone, oxycodone, codeine, tramadol, morphine, and hydrocodone. All opioid dosages were converted into morphine equivalent dosages for analysis. Each patient began physical therapy within the first 24 hours postoperatively. Patients were discharged when they were able to begin self-care, their pain was controlled utilizing an oral regimen, and they were able to tolerate oral medication intake.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Adventist Hinsdale Hospital
    • Westmont, Illinois, United States, 60559
      • American Hip Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients scheduled to undergo primary unilateral total hip replacement
• Patients diagnosed with hip osteoarthritis
• Patients failed to improve with conservative measures
• Patients willing and able to sign informed consent

Exclusion Criteria:

• Revision total hip replacement
• Bilateral total hip replacement
• Birmingham hip resurfacing
• Patients with hepatic/kidney disease
• Patients with a known allergy to bupivacaine or other local anesthetics

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liposomal bupivacaine; Periarticular infiltration cocktail of 20cc of liposomal bupivacaine with 20cc of normal saline and 40cc of 0.25% bupivacaine with epinephrine	Drug: Liposomal Bupivacaine; 266mg liposomal bupivacaine; Other Names: Exparel; Drug: 0.25% Bupivacaine with epinephrine; 0.25% bupivacaine with epinephrine; Other Names: Marcaine; Drug: Saline; Normal saline; Other Names: Saline solution
Active Comparator: Bupivacaine with epinephrine; Periarticular infiltration cocktail of 60cc of 0.25% bupivacaine with epinephrine	Drug: 0.25% Bupivacaine with epinephrine; 0.25% bupivacaine with epinephrine; Other Names: Marcaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Morphine Equivalent Consumption	All opioid doses were administered to the patient at 12-hour intervals post-surgery. Doses were recorded till either of the following criteria was met, the patient was discharged or the 72-hour post-surgery timeframe ended. The doses were then collected and converted to OMEs, in milligrams.	72 hours postoperation, divided into six 12-hour periods
Change in Patient-reported Visual Analog Scale (VAS) Pain Intensity Score	Patient-reported VAS pain intensity score (0 = no pain, 10 = worst pain possible) will be collected. Mean VAS scores for the 72-hour period were calculated using the cohort's reported average pain scores at each 12-hour interval.	72 hours post-operation, divided into six 12-hour periods
Time to Ambulation More Than 20 Feet (in Hours)	The length of time (in hours) until the patient first ambulates more than 20 feet from the time of surgery will be recorded.	from time of surgery until patient first ambulates more than 20 feet or 72 hours post-surgery or patient discharge, whichever comes first
Length of Stay (LOS, in Days)		From time of surgery until patient is discharged, an average of 1.5 days.
Number of Patients That Experienced a Fall		72 hours postoperation

Collaborators and Investigators

• Sponsor: American Hip Institute
• Investigators: Principal Investigator: Benjamin G Domb, MD, American Hip Institute

Publications and helpful links

General Publications

• Perets I, Walsh JP, Mu BH, Yuen LC, Ashberg L, Battaglia MR, Domb BG. Intraoperative Infiltration of Liposomal Bupivacaine vs Bupivacaine Hydrochloride for Pain Management in Primary Total Hip Arthroplasty: A Prospective Randomized Trial. J Arthroplasty. 2018 Feb;33(2):441-446. doi: 10.1016/j.arth.2017.09.013. Epub 2017 Sep 20.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: November 8, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: bupivacaine; total hip replacement; Exparel
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Bupivacaine; Epinephrine
• Other Study ID Numbers: AHI-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO