A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty

• Published in: The knee Vol. 19; no. 5; pp. 530 - 536
• Main Authors: Bramlett, Kenneth, Onel, Erol, Viscusi, Eugene R, Jones, Kevin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2012; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Analgesia - methods; Anesthesia, Local - methods; Anesthetics, Local - administration & dosage; Anesthetics, Local - pharmacokinetics; Arthroplasty, Replacement, Knee; Bupivacaine - administration & dosage; Bupivacaine - pharmacokinetics; Clinical trial; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; DepoFoam bupivacaine; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Drug therapy; Family medical history; Female; Follow-Up Studies; Humans; Joint surgery; Knee; Liposomes; Male; Middle Aged; Orthopedics; Pain management; Pain, Postoperative - drug therapy; Pain, Postoperative - metabolism; Pharmaceuticals; Postsurgical analgesia; Prospective Studies; Standard deviation; Surgery; Total knee arthroplasty; Treatment Outcome; Wound infiltration; Young Adult; Clinical trial; Total knee arthroplasty; Postsurgical analgesia; DepoFoam bupivacaine; Wound infiltration
• ISSN: 0968-0160; 1873-5800
• DOI: 10.1016/j.knee.2011.12.004

Abstract Introduction DepoFoam bupivacaine is a novel liposomal formulation of bupivacaine designed to provide prolonged postsurgical analgesia. This dose-ranging study evaluated extent and duration of analgesia following administration of DepoFoam bupivacaine in patients undergoing total knee arthroplasty (TKA). Methods Efficacy, safety, and pharmacokinetics of DepoFoam bupivacaine doses of 133, 266, 399, or 532 mg were compared with bupivacaine HCl (150 mg) with epinephrine given as single injections via wound infiltration in TKA patients (N = 138). Primary efficacy measure was AUC of pain intensity scores assessed by numeric rating scale with activity (NRS-A) through Day 4 postsurgery. Other assessments included pain intensity at rest (NRS-R), postsurgical opioid consumption, and safety, among others. Results Mean AUC of NRS-A scores through Day 4 were 20.7, 19.5, 18.8, and 19.1 for the 133-mg, 266-mg, 399-mg, and 532-mg DepoFoam bupivacaine groups vs 20.4 for bupivacaine HCl. With DepoFoam bupivacaine 532-mg, differences in NRS-R scores reached statistical significance ( P < 0.05) vs bupivacaine HCl on Days 1 and 5 and mean AUC NRS-R scores were significantly lower through Days 2–5; a dose–response trend was demonstrated. Mean rating for blinded care provider's satisfaction with analgesia was significantly higher for DepoFoam bupivacaine 532 mg vs bupivacaine HCl ( P ≤ 0.05). Other efficacy measures showed no statistically significant differences. Conclusion Exposure to bupivacaine increased in a dose-related manner, as reflected by mean and maximum plasma bupivacaine concentrations, and AUC 0 − ∞ . Treatment with DepoFoam bupivacaine 532 mg was associated with statistically significantly greater analgesia while patients were at rest after surgery compared with bupivacaine HCl.