Treatment of postoperative pain in shoulder surgery with SABER-Bupivacaine

Abstract

SABER-Bupivacaine (SB) is a long-acting depot formulation designed to deliver bupivacaine to surgical wounds over a 72 hour period to effectively control postoperative pain. SB is administered directly into the surgical wound in a 5 mL volume containing 660 mg of bupivacaine. SB was evaluated in a multicenter, double-blind, placebo and active controlled trial of 107 patients undergoing laparoscopic subacromial decompression surgery under general anesthesia. Efficacy co-primary endpoints were 1.) Pain intensity (PI) on shoulder movement assessed with a NRS at scheduled time points over 1-72 hours post-surgery expressed as time normalized AUC and 2.) Total rescue opioid use over 0-72 hours expressed as IV morphine equivalents. Patients were randomized in a 2:1:1 ratio to 5 mL SB (53 pts.), to bupivacaine-HCl, 20 mL of 0.25% (BUP) (29 pts.), or to SABER-Placebo, 5 mL (SP) (25 pts.). In addition to prn opioid rescue, all patients were given acetaminophen as preemptive analgesia (2-4 gm/day depending on body weight). The mean (SD) PI AUC1-72 was 5.16 (1.94) for SB, 5.16 (2.38) for BUP, and 6.43 (1.77) for SP (ANOVA p=0.012 SB vs. SP). SB significantly reduced PI AUC on post-operative days 1 and 2 compared to SP. In a repeated measures analysis, SB was statistically superior to BUP over the first 12 hours (p=0.01) and trended significant at 24 hours (p=0.07). Median morphine equivalents taken over 0-72 hours were 4.0 mg for SB, 8.0 mg for BUP, and 12.0 mg for SP (Wilcoxon p=0.013 SB vs. SP). All patients completed the trial normally and incidence of AEs was similar between treatment groups. The most frequent AEs were headache, nausea and musculoskeletal pain. Study supported by Nycomed and abstract by Durect. SABER-Bupivacaine (SB) is a long-acting depot formulation designed to deliver bupivacaine to surgical wounds over a 72 hour period to effectively control postoperative pain. SB is administered directly into the surgical wound in a 5 mL volume containing 660 mg of bupivacaine. SB was evaluated in a multicenter, double-blind, placebo and active controlled trial of 107 patients undergoing laparoscopic subacromial decompression surgery under general anesthesia. Efficacy co-primary endpoints were 1.) Pain intensity (PI) on shoulder movement assessed with a NRS at scheduled time points over 1-72 hours post-surgery expressed as time normalized AUC and 2.) Total rescue opioid use over 0-72 hours expressed as IV morphine equivalents. Patients were randomized in a 2:1:1 ratio to 5 mL SB (53 pts.), to bupivacaine-HCl, 20 mL of 0.25% (BUP) (29 pts.), or to SABER-Placebo, 5 mL (SP) (25 pts.). In addition to prn opioid rescue, all patients were given acetaminophen as preemptive analgesia (2-4 gm/day depending on body weight). The mean (SD) PI AUC1-72 was 5.16 (1.94) for SB, 5.16 (2.38) for BUP, and 6.43 (1.77) for SP (ANOVA p=0.012 SB vs. SP). SB significantly reduced PI AUC on post-operative days 1 and 2 compared to SP. In a repeated measures analysis, SB was statistically superior to BUP over the first 12 hours (p=0.01) and trended significant at 24 hours (p=0.07). Median morphine equivalents taken over 0-72 hours were 4.0 mg for SB, 8.0 mg for BUP, and 12.0 mg for SP (Wilcoxon p=0.013 SB vs. SP). All patients completed the trial normally and incidence of AEs was similar between treatment groups. The most frequent AEs were headache, nausea and musculoskeletal pain. Study supported by Nycomed and abstract by Durect.