A new large meta-analysis was published. The results showed the likelihood that liposomal bupivacaine and nerve blocks no longer offer significant contribution. Decision was made to terminate the study.

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

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.

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.