Thermal Stress Potentiates Bupivacaine Chondrotoxicity

Abstract

The primary objective of this study was to determine whether thermal stress potentiates the chondrotoxic effect of bupivacaine, resulting in decreased articular chondrocyte viability compared with exposure to bupivacaine alone. Bovine articular cartilage explants and cultured chondrocytes were treated with a range of thermal exposures (10 to 20 minutes at 37°C to 65°C) to create time/temperature viability curves and to determine threshold conditions for cell death. A second set of experiments was performed to determine whether subthreshold thermal stress potentiates bupivacaine toxicity. Explants were exposed to 37°C or 55°C for 10 or 20 minutes, and cultured chondrocytes were exposed to 37°C or 45°C for 10 or 20 minutes. Thirty minutes later, the explants and chondrocytes were treated with either 0.9% normal saline solution or 0.5% bupivacaine for 30 minutes. Chondrocyte viability was quantified 24 hours after treatment. There was a temperature- and time-dependent decrease in chondrocyte viability above the thermo-toxicity threshold in both intact cartilage explants and cultured chondrocytes (55°C and 45°C, respectively; P < .05). Chondrocyte viability in cartilage explants was significantly lower after treatment with thermal stress for 10 or 20 minutes followed by bupivacaine for 30 minutes compared with treatment with bupivacaine at 37°C (bupivacaine and 55°C for 10 minutes, 0.09% ± 0%; bupivacaine and 55°C for 20 minutes, 0.08% ± 0%; bupivacaine and 37°C for 10 minutes, 37.4% ± 1.2% [P < .001]; and bupivacaine and 37°C for 20 minutes, 47.1% ± 0.8% [P < .001]). A similar trend was seen in cultured chondrocytes, although it was not statistically significant (P > .05). Thermal stress potentiates the chondrotoxic effects of bupivacaine in intact cartilage, leading to decreased chondrocyte viability compared with exposure to bupivacaine alone. Intra-articular injection of bupivacaine after arthroscopic procedures during which cartilage is exposed to elevated temperatures, such as with prolonged use of radiofrequency probes, may increase the risk of chondrocyte toxicity.