Is Chemical Incompatibility Responsible for Chondrocyte Death Induced by Local Anesthetics?

Background: Chondrolysis associated with intra-articular administration of local anesthetics has been attributed to chondrocyte death induced by the local anesthetics. The mechanism of how the local anesthetics cause chondrocyte death is not clear. Purpose: This study was conducted to determine whether and how the local anesthetics cause chondrocyte death. Study Design: Controlled laboratory study. Methods: Bovine articular chondrocytes in suspension culture were treated for 1 hour with phosphate-buffered saline or phosphate-buffered saline/medium mixture (as controls); 1% lidocaine alone; 0.25% to 0.5% bupivacaine alone; phosphate-buffered saline with pH values of 4.5, 3.8, 3.4, and 2.4; or mixtures of the local anesthetics and cell culture medium or human synovial fluid. Chondrocyte viability was analyzed by flow cytometry using the LIVE/DEAD Viability/Cytotoxicity Kit. Results: In 1% lidocaine-alone or 0.25% to 0.5% bupivacaine-alone groups, the rate of cell death was 11.8% to 13.3% of bovine articular chondrocytes, whereas the phosphate-buffered saline control had 8.4% of cell death. Increased chondrocyte death was only found when the pH value of phosphate-buffered saline dropped to ≤3.4. In contrast, when bupivacaine was mixed with cell culture medium, needle-like crystals were formed, which was accompanied with 100% death of chondrocytes. Lidocaine did not form visible crystals when it was mixed with culture medium, but the mixtures caused death of over 96% of chondrocytes (P <.001). Conclusion: Less than 5% of chondrocyte death was attributable to the anesthetics when applied to the cells alone or in phosphate-buffered saline-diluted solution. Acidity (as low as pH 3.8) or epinephrine in the anesthetic solutions could not account for chondrocyte death. However, chemical incompatibility between the local anesthetics and cell culture medium or human synovial fluid may be the cause of chondrocyte death. Clinical Relevance: Intra-articular administration of lidocaine and bupivacaine is not an indicated usage of either anesthetic, although such a usage has become a common practice. Physicians should be aware of the potential incompatibility of the drug and synovial fluid.