Improving Pain Management After Total Shoulder Replacement Using Bupivacaine Liposome

To improve pain control and decrease opioid requirements for subjects undergoing Total Shoulder Replacement.

Study Overview

• Status: Withdrawn
• Conditions: Pain, Postoperative; Shoulder Pain; Osteoarthritis of the Shoulder
• Intervention / Treatment: Drug: Bupivacaine Liposome Injection; Other: Standard Therapy

Detailed Description

For the pilot study the investigators will use a total of 20 cases per group.

A HIPAA Waiver will be used for screening purposes. The investigators will be using the electronic medical record system (EPIC) to screen for subjects in the University of Massachusetts Medical (UMass) system.

Subjects will be recruited and consented as described later in the study plan.

Subjects will be randomized to the two groups (standard therapy or BL) using a random number generator. The random number with the type of anesthetic will stored in envelopes and will be opened in sequence on each day of the interscalene nerve block (ISNB).

1. Group 1: Standard therapy

   1. Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, or age as currently determined by acute pain service (APS) anesthesiologist)
   2. Preoperative, ultrasound guided ISNB with a bupivacaine mixture: 20ml 0.5% bupivacaine and epinephrine 1:200,000.

2. Group 2: BL

   1. Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, age, or current therapy as currently determined by APS anesthesiologist)
   2. Pre-operative ultrasound guided ISNB with a 20ml mixture consisting of 10ml of 0.5% bupivacaine with epinephrine 1:200,000, and 10ml of BL 1.33%

In accordance with our current practice, all subjects will have premedication with midazolam and fentanyl and general anesthesia (GA) with endotracheal tube (ETT). Propofol will be used for induction of GA. During surgery, administration of short acting narcotics (fentanyl) will be at the discretion of the anesthesia team.

As BL will be used, no additional local anesthetics will be used during surgery (i.e. lidocaine for induction or maintenance of anesthesia, or local anesthetics for infiltration in the surgical field). Ketamine will not be used as an anesthetic / analgesic adjunct

After this, all patients will remain on our standard protocols. In the PACU, subjects will receive IV hydromorphone for pain control. Once on the post- operative floor, subjects pain will be managed with oxycodone as needed every 4 hours (5mg for moderate pain, 10mg for severe pain) and 0.4 mg IV hydromorphone for breakthrough pain.

Subject's postoperative opioid consumption and pain scores will be obtained from their charts. Subjects will fill out a Brief Pain Inventory Short Form pre-operatively, on post-operatively day (POD) 1, and POD 2 (if the patients have not been discharged from the hospital).

Blinding In this study, the investigators will work with the Investigational Drug Pharmacy, who will store the medications, and supply medications on the day of surgery. Subjects will be blinded, as all subjects will receive an ISNB. The surgeon, anesthesiology team, post-anesthesia care unit (PACU) and floor nurses will also be unaware of group assignment, and will use their clinical judgement and subjects' reporting when administering medications and recording pain scores. Surveys about subjects' satisfaction with pain control, as well as data collection from subjects' records will be done by study investigators that are not involved in performing injections.

The Anesthesiologists performing the nerve block will not be blinded (as the Bupivacaine Liposome solution is a suspension and is white, whereas bupivacaine solution is clear), but will not participate in further evaluations of the subjects or data collection.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adult subjects older than 18years old undergoing Total Shoulder Replacement (TSR) or reverse TSR surgery.
2. Meet criteria for regional nerve block.
3. Weight greater than 60kg (safety to keep liposomal bupivacaine and bupivacaine dosing below 3mg/kg).

Exclusion Criteria:

1. Recent drug use
2. Subjects on chronic buprenorphine therapy (either for opioid replacement or pain control).
3. Nerve injury (cervical stenosis, trauma, etc) of the surgical limb.
4. Coagulopathy
5. Subjects with significant liver disease (as amide type local anesthetics such as bupivacaine are metabolized by the liver).
6. Infection near or in the area of the nerve block.
7. Subject refusal of regional anesthesia.
8. Vulnerable populations (prisoners, mental impairment / dementia, etc).
9. Subjects requiring interpreter services (not proficient in English).
10. Subjects with poor cardio-pulmonary reserve who might not tolerate a hemi-diaphragmatic paralysis or hemi-diaphragmatic paresis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bupivacaine Liposome; Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, age, or current therapy as currently determined by APS anesthesiologist).; Pre-operative ultrasound guided ISNB with a 20ml mixture consisting of 10ml of 0.5% bupivacaine with epinephrine 1:200,000, and 10ml of BL 1.33%	Drug: Bupivacaine Liposome Injection; Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, age, or current therapy as currently determined by APS anesthesiologist); Pre-operative ultrasound guided ISNB with a 20ml mixture consisting of 10ml of 0.5% bupivacaine with epinephrine 1:200,000, and 10ml of BL 1.33%; Other Names: Standard Therapy and Bupivacaine Liposome 10ml 1.33%
Active Comparator: Standard therapy; Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, or age as currently determined by acute pain service (APS) anesthesiologist).; Preoperative, ultrasound guided ISNB with a bupivacaine mixture: 20ml 0.5% bupivacaine and epinephrine 1:200,000.	Other: Standard Therapy; Standard pre-operative and post-operative medical regimen including standing acetaminophen 650mg q6hours, gabapentin 300mg q8hours and as needed oxycodone every 4 hours (unless there are contraindications due to liver function, kidney function, or age as currently determined by acute pain service (APS) anesthesiologist); Preoperative, ultrasound guided ISNB with a bupivacaine mixture: 20ml 0.5% bupivacaine and epinephrine 1:200,000.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Equivalent Dose of Opioids	Morphine equivalent dose (MED) of opioids within the first 24 hours after surgery (including PACU and medications on the floor)	First 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine equivalent dose of opioids	Morphine equivalent dose (MED) of opioids within the first 24-48 hours after surgery (including PACU and medications on the floor)	24-48 hours
Visual Analogue Scale Pain Score	Visual Analogue Scale Pain Score (VAS) in the first 24 hours, and 24-48 hours after surgery	24-48 hours
Hospital Length of Stay	Hospital Length of Stay	Through study completion, an average of 2-3 days
Post-Operative Brief Pain Inventory Short Form	Brief Pain Inventory Short Form pre-operatively on POD 0, POD 1, and POD 2	<1 day, 1 day, and 2 days
Cost Analysis	Cost estimate of each technique	Through study completion, an average of 2-3 days
Opioid Administration	Time to administration of the first opioid	Up to 72 hours

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Investigators: Principal Investigator: Alexander Chan, MD, University of Massachusetts Chan Medical School

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): September 23, 2021
• Study Completion (Actual): September 23, 2021

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Pain Management; Exparel; Total Shoulder Replacement; Bupivacaine Liposome
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia; Pain, Postoperative; Shoulder Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: H00016941

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