We will be performing site maintenance on our learning platform at learn.aaos.org on Sunday, February 5th from 12 AM to 5 AM EST. We apologize for the inconvenience.


Published 4/1/2017
Terry Stanton

Study: No Advantage to Liposomal Bupivacaine for TKA

A study comparing the effect of the use of liposomal bupivacaine versus ropivacaine in total knee arthroplasty (TKA), found no increased benefit of liposomal bupivacaine for postoperative pain control.

The prospective, double-blind study, was presented by Jeffrey H. DeClaire, MD, of Ascension Crittenton Medical Center, Rochester Hills, Mich., during the AAOS Annual Meeting. The authors randomized 96 patients undergoing unilateral TKA into two groups. Patients in the first group (control, n = 49) received a standard periarticular 100 mL “pain cocktail” injection of ropivacaine, ketorolac, morphine, and epinephrine in saline. Patients in the second group (experimental, n = 47) received a similar cocktail with bupivacaine substituted in an 80 mL preparation, plus a 20 mL injection of liposomal bupivacaine (1.3 percent). The pharmacist gave the “cocktail” to the operating nurse for injection by the surgeon. The method of application was standardized between the two groups. A 22-gauge spinal needle was used to inject the 100 mL preparation into the periarticular soft-tissue envelope. Half was distributed to the deep soft tissues, including the posterior capsule, medial and lateral capsule, and the collateral ligaments. The synovial tissue and periosteum were also injected circumferentially on the femur and the tibia. Before wound closure, the other 50 mL were infiltrated into the subcutaneous tissues.  Effectiveness of postoperative pain control was measured in terms of postoperative use of opiates and mean time to ambulate 100 feet. Patients were treated with the same postoperative pain management protocol and the same postoperative physical therapy program in the hospital. The investigators recorded Visual Analog Scale (VAS) scores for pain preoperatively and postoperatively during the hospital stay. The consumption of oral and intravenous narcotics at specific time points, as well as total use, hours to ambulate 100 feet, and length of hospital stay were recorded. Both the investigator and the patient were blinded to treatment group. Before beginning the postoperative analysis, the authors conducted a preoperative analysis comparing the analgesic (nonsteroidal anti-inflammatory drug [NSAID]) usage and VAS score for pain between the control and experimental group. There was no significant difference for either preoperative parameter, so the patients in both groups were judged to be similar enough to conduct the postoperative analysis. Opioid consumption mostly similar On a per-hour basis, the mean use of narcotics of the two groups differed by only 0.1 mg, said Dr. DeClaire. For total narcotic use during hospital stay, the weighted sum used by patients in the liposomal bupivacaine group, 97.7 mg of hydrocodone ±42.84 mg, exceeded the weighted sum, 89.6 mg of hydrocodone ±58.57 mg, used by patients in the control group. The difference, however, was not statistically significant (P < 0.443). The only significant difference in narcotic use was found with Norco (hydrocodone and acetaminophen); the patients in the liposomal bupivacaine group used significantly more Norco than the patients in the control group (P < 0.043). The mean lengths of stay differed by only 26 minutes. The mean time to ambulate 100 feet differed by 53 minutes. The two groups did not differ for VAS score for pain on day 1 or day 2 postoperatively. The liposomal bupivacaine group took longer to ambulate and reported higher pain scores on post-op day 1. None of these differences was statistically significant. Furthermore, there was no statistically significant difference in the amount of NSAIDs consumed postoperatively during the hospital stay (P < 0.641). No adverse reactions were reported in either group. The current epidemic of opioid addiction, as well as awareness of the adverse effects of sanctioned opioid use, including delayed physical therapy, prolonged hospital stay, and related readmission, has led to heightened interest in alternative pain control approaches. Multimodal pain management, combining analgesic agents with differing modes of action that can work synergistically to manage pain, “has shown promise when used as a periarticular injection in TKA and has become a recommended postoperative method of pain control as it lowers use of opioid analgesics and lessens the use of patient-controlled analgesics postoperatively,” the authors write. “This study, however, indicates that although liposomal bupivacaine reportedly provides an advantage over femoral nerve block in TKA, it does not offer any benefit when compared to ropivacaine in periarticular injection as part of multimodal pain management.” Dr. DeClaire said that he and his colleagues were prompted to do the study because “we were excited about the opportunity to show the efficacy of this new method for postoperative pain management in the total knee patient. We also were getting significant push back from our hospital administration because of the significant increase in cost of liposomal bupivacaine.” Of the results, he said, “We were expecting to show improved outcomes with the Exparel® (liposomal bupivacaine) patient group. To our surprise, we actually found no significant difference between the control group and the study group.” The clinical takeaway, he said, “is that the significant increase in costs associated with the use of Exparel for the treatment of postsurgical pain in the total knee arthroplasty patient is not warranted. This is particularly significant with regard to the Bundled Payment Initiative, with the goals of minimizing cost of care while maintaining high quality of care.” Dr. DeClaire noted that this study is limited to the immediate follow-up of patients following TKA. “Further, ongoing evaluation is needed to determine if any differences between the groups manifest in the long term. There is very little data on the utilization of this drug with regional nerve blocks and the use of pain pumps for prolonged pain management, particularly in the outpatient setting,” he said.      Dr. DeClaire's coauthors of “Effectiveness of Bupivacaine Liposome Injectable Suspension for Postoperative Pain Control in Total Knee Arthroplasty: A Prospective, Randomized, Double Blind, Controlled Study,” are Paige M. Aiello, MS, and D. Carl Freeman, PhD. Details of the authors' disclosures as submitted to the Orthopaedic Disclosure Program can be found in the Final Program; the most current disclosure information may be accessed electronically at www.aaos.org/disclosure Terry Stanton is the senior science writer for AAOS Now. He can be reached at tstanton@aaos.org

Bottom Line

  • This prospective, double-blind study compared patients undergoing TKA and receiving injection of ropivacaine, ketorolac, morphine, and epinephrine with those who received a mixture in which the ropivacaine was substituted with bupivacaine and liposomal bupivacaine.
  • No significant difference in postoperative consumption of hydrocodone or length of stay was seen between the patient groups.
  • The findings contradicted the author's expectation that patients receiving liposomal bupivacaine would decrease early post-operative pain, time to ambulation, and length of stay.
  • The findings suggest that the markedly increased cost of use of Exparel (liposomal bupivacaine) is not warranted in this setting.