Abstract
Objective The purpose of this study is to determine whether (1) liposomal bupivacaine is chondrotoxic; (2) the chondrotoxicity of liposomal bupivacaine differs from standard bupivacaine; and (3) chondrotoxic effects are time dependent. Materials and Methods We obtained 72 10 mm articular cartilage plugs from 12 fresh bovine distal femoral knee joints and exposed them to either saline, 0.5% bupivacaine, or liposomal bupivacaine for either 30 or 90 minutes. Twenty-four hours after treatment, chondrocyte viability was measured with the use of a fluorescent live/dead assay. An ANOVA test of variance was performed followed by a Holm–Sidak test to make pairwise comparisons across conditions. Student's t-test was used to compare means. Results Percent viability of cells exposed to liposomal bupivacaine for 30 minutes was less versus saline control (53.9% ± 21.5% vs. 73.7 ± 18.4%, p=0.035), and this remained significant at 90 minutes (49.1% ± 20.3% vs. 67.2% ± 25.6%, p < 0.001). Liposomal bupivacaine had less chondrotoxic effects when compared with bupivacaine after 90 minutes, with greater viability (49.1% ± 20.3% vs. 21.4% ± 14.0%, p=0.003). Chondrotoxicity was found to be time dependent within the bupivacaine group (percent viability at 30 min: 45.5 ± 18.2%, 90 min: 21.4 ± 14.0%, p=0.001); however, liposomal bupivacaine did not demonstrate a significant time-dependent chondrotoxic relationship (p=0.583). Conclusions Bupivacaine and liposomal bupivacaine are both toxic to chondrocytes. Liposomal bupivacaine is less chondrotoxic than standard bupivacaine and does not demonstrate a time-dependent toxicity.
Highlights
Intra-articular injections of local anesthetics are commonly used for managing pain associated with degenerative joint disease, as well as pain associated with arthroscopic procedures. ey have been used for many years and have been shown to be efficacious in the ambulatory setting for diagnostic and therapeutic purposes
Investigators have found that bupivacaine and other local anesthetics are toxic to chondrocytes, and in vitro and in vivo studies have shown that even brief exposures result in decreased chondrocyte metabolism, increased chondrocyte apoptosis and necrosis, and gross morphologic cartilage degradation [2,3,4,5,6,7,8]
When compared with saline control, percent viability in plugs exposed to liposomal bupivacaine at 30 minutes was less (73.7 ± 18.4% vs. 53.9% ± 21.5%, p 0.035)
Summary
Intra-articular injections of local anesthetics are commonly used for managing pain associated with degenerative joint disease, as well as pain associated with arthroscopic procedures. ey have been used for many years and have been shown to be efficacious in the ambulatory setting for diagnostic and therapeutic purposes. Intra-articular injections of local anesthetics are commonly used for managing pain associated with degenerative joint disease, as well as pain associated with arthroscopic procedures. Concern has risen regarding complications associated with intra-articular injections in arthroscopic procedures involving healthy cartilage. Investigators have found that bupivacaine and other local anesthetics are toxic to chondrocytes, and in vitro and in vivo studies have shown that even brief exposures result in decreased chondrocyte metabolism, increased chondrocyte apoptosis and necrosis, and gross morphologic cartilage degradation [2,3,4,5,6,7,8]. Pain pump models have shown gross cartilage necrosis after sustained exposure to local anesthetic infusion [9]. Our null hypothesis was that liposomal bupivacaine was neither chondrotoxic nor had time-dependent toxicity
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