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Liposomal Bupivacaine Shows Similar Length of Pain Relief as Standard Bupivacaine With Dexamethasone After Shoulder Surgery

A new Hospital for Special Surgery (HSS) study has found that liposomal bupivacaine appears non-inferior to standard bupivacaine with dexamethasone for pain relief following shoulder surgery. Researchers concluded that bupivacaine with dexamethasone can be used interchangeably with liposomal bupivacaine for pain relief in nerve blocks for these procedures, and that due to cost differences, bupivacaine with dexamethasone is often the better choice. These findings were presented at the 2022 Spring American Society of Regional Anesthesia and Pain Medicine (ASRA) Annual Meeting and acknowledged as one of the Best of Meeting Abstracts.1

The U.S. Food & Drug Administration recently approved liposomal bupivacaine for use in interscalene nerve blocks. Liposomal bupivacaine is an extended-release formulation of bupivacaine that theoretically sustains pain relief up to 72 hours. However, there is a lack of randomized controlled trials comparing liposomal bupivacaine with placebo (saline) or with “standard” bupivacaine. 

Investigators aimed to determine whether liposomal bupivacaine actually prolongs pain relief compared with standard bupivacaine plus dexamethasone as a regional anesthetic technique. HSS has been using standard bupivacaine with perineural dexamethasone as an adjuvant in order to lengthen pain relief from nerve blocks up to 30 hours, as there are several meta-analyses and systematic reviews supporting its safe and effective use in upper extremity blockade. This study is the first randomized controlled trial comparing the two drugs as injectates in nerve blocks.

Study on prolonging nerve blocks is imperative, as “prolonging analgesia with adjuvants may be key in decreasing opioid use after surgery,” said Dr. David Kim, anesthesiologist at HSS.

The study was conducted from August 2019 to March 2021 in 112 patients undergoing ambulatory shoulder surgery. Participants were divided into two groups: 56 patients who received a mixture of 5 mL of 0.5% standard bupivacaine with 133 mg of liposomal bupivacaine; and 55 patients who received a mixture of 15 mL of 0.5% standard bupivacaine with 4 mg of dexamethasone. 

The primary outcome was average numerical rating scale (NRS) pain scores at rest over a period of 72 hours, but the researchers also examined analgesic block duration, motor and sensory resolution, opioid use, and NRS pain scale scores when resting and moving on days 1, 4 and 7 after surgery. They also examined patient satisfaction, readiness for PACU discharge, and adverse side effects related to the interscalene block. 

The results indicated that the pain score after 72 hours in the liposomal bupivacaine group was non-inferior to the bupivacaine with dexamethasone group (mean (SD), 2.4 (1.9) versus 3.4 (1.9), mean difference (95%CI), -1.1 (-1.8, -0.4), p <0.001 for noninferiority). Additionally, there was also no significant difference in the length of pain relief between the two groups. Furthermore, there was no difference in opioid consumption, readiness for PACU discharge, or adverse events. 

“Liposomal bupivacaine is noninferior to preservative-free dexamethasone when used as an adjuvant for the interscalene nerve block,” Dr. Kim noted. “Even though there was a statistically significant difference in the pain scores, the differences are unlikely to be clinically relevant. As practicing clinicians, it was important for us to investigate interventions that provide meaningful clinical differences, not to only look for statistical significance in numbers.”

Dr. Kim concluded “Follow up research should include a large prospective randomized controlled trial comparing liposomal bupivacaine and preservative-free dexamethasone on total shoulder arthroplasties.”


1. Danya A. DeMeo BS, Ejiro Gbaje MPH, Jacques T. YaDeau MD PhD, Kethy M. Jules-Elysee MD, Yi Lin MD PhD, Enrique A. Goytizolo MD, David Kim MD, Richard L Kahn MD, Stephen C. Haskins MD, David J. Mayman MD, Douglas E. Padgett MD, Thomas P. Sculco MD, Chad M. Brummett MD, Geoffrey Westrich MD. “Interscalene brachial plexus block with liposomal bupivacaine versus standard bupivacaine with perineural dexamethasone: a noninferiority trial.” Presented at: 47th Annual Regional Anesthesiology and Acute Pain Medicine Meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA), March 31-April 2, 2021; Las Vegas, NV.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.