Novel Depot Bupivacaine Formulation Reduced Pain After Arthroscopic Subacromial Decompression

Sucrose acetate isobutyrate extended-release (SABER™)-bupivacaine reduces postoperative pain and opioid consumption among patients undergoing arthroscopic subacromial decompression (ASD), according to study findings published in Journal of the AAOS Global Research & Reviews.

SABER-Bupivacaine is a depot bupivacaine formulation designed to provide surgical site analgesia for up to 72 hours.

Patients undergoing elective ASD for impingement syndrome at 9 sites in 5 European countries were enrolled in the study. Patients were randomly assigned 2:1:1 to receive 5 mL SABER-Bupivacaine with 660 mg active bupivacaine, 5 mL SABER-Bupivacaine vehicle without active bupivacaine (placebo control), or 50 mg active bupivacaine (active control) administered subacromially prior to skin closure.

All patients received oral paracetamol for 72 hours at the maximum dose and 10 mg oral morphine at 1-hour intervals as needed. After 72 hours, paracetamol and oral morphine were administered as needed.

The primary study endpoints were pain intensity on 90° shoulder flexion and opioid consumption.

A total of 107 patients (53 in the SABER-Bupivacaine group; 25 in the placebo control group, and 29 in the active control group) were included in the study. The mean age of participants was 50.2 years; 60% were women.

The time-normalized area under the curve (AUC) during the first 72 hours after surgery (nAUC_1-72) was 5.16 for the SABER-Bupivacaine cohort, 6.43 for the SABER-Bupivacaine vehicle control (P =.012) cohort, and 5.16 for the active bupivacaine control cohort. The least-squares mean of pain intensity for the first 72 hours was significantly lower for the SABER-Bupivacaine group compared with the placebo control group (4.8 vs 6.6; P =.0001) and numerically lower than the active control group (5.3).

The SABER-Bupivacaine group required a median of 4.0 mg rescue opioids compared with 12.0 mg for the placebo control group (P =.010) and 8.0 mg for the active control group. The time-to-first opioid rescue was 12.4 hours for the SABER-Bupivacaine group, 1.2 hours for the placebo control group (P =.014), and 1.4 hours for the active control group. A higher percentage of SABER-Bupivacaine recipients remained opioid-free (39.6%) compared with those in the placebo control (16.0%; P =.027) and the active control (27.6%) groups.

A total of 37 patients reported a total of 65 treatment-emergent adverse events (TEAEs). Patients in the SABER-Bupivacaine, placebo control, and active control cohorts reported similar rates of TEAEs (30.2% vs 40.0% vs 37.9%, respectively). Most events were mild or moderate in severity. None of the patients withdrew from the study due to TEAEs.

At 6 months, 101 patients underwent magnetic resonance imaging (MRI). No notable changes from baseline or safety concerns were observed. Constant-Murley functionality improved from an average of 44.7 to 61.6 in the SABER-Bupivacaine group, 41.7 to 63.2 in the placebo control group, and 42.0 to 65.6 in the active control group.

One of the study limitations was that it was not designed to detect significant differences between the SABER-Bupivacaine and active control groups.

“The reduced opioid consumption that accompanied SABER-Bupivacaine treatment supports the contention that the observed pain relief was clinically meaningful,” the researchers noted.

Disclosure: This research was supported by Nycomed. Please see the original reference for a full list of disclosures.

Reference

Ekelund A, Peredistijs A, Grohs J, Meisner J, Verity N, Rasmussen S. SABER-Bupivacaine reduces postoperative pain and opioid consumption after arthroscopic subacromial decompression: a randomized, placebo-controlled trial. J Am Acad Orthop Surg Glob Res Rev. 2022;6(5). doi:10.5435/JAAOSGlobal-D-21-00287