Tulane Institute of Sports Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Am J Sports Med. 2010 Mar;38(3):520-6. doi: 10.1177/0363546509349799.
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 < or = 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.
背景：关节内局部麻醉剂的使用与软骨溶解有关，这归因于局部麻醉剂诱导的软骨细胞死亡。然而，局部麻醉剂如何引起软骨细胞死亡的机制尚不清楚。
目的：本研究旨在确定局部麻醉剂是否以及如何引起软骨细胞死亡。
研究设计：对照实验室研究。
方法：悬浮培养的牛关节软骨细胞用磷酸盐缓冲盐水或磷酸盐缓冲盐水/培养基混合物（作为对照）；单独 1%利多卡因；单独 0.25%至 0.5%布比卡因；pH 值为 4.5、3.8、3.4 和 2.4 的磷酸盐缓冲盐水；或局部麻醉剂和细胞培养基或人滑膜液的混合物。使用 LIVE/DEAD 活力/细胞毒性试剂盒通过流式细胞术分析软骨细胞活力。
结果：在 1%利多卡因单独或 0.25%至 0.5%布比卡因单独组中，牛关节软骨细胞的细胞死亡率为 11.8%至 13.3%，而磷酸盐缓冲盐水对照的细胞死亡率为 8.4%。仅当磷酸盐缓冲盐水的 pH 值降至<或=3.4 时，才会发现软骨细胞死亡增加。相比之下，当布比卡因与细胞培养基混合时，会形成针状晶体，同时伴有软骨细胞 100%死亡。利多卡因与培养基混合时不会形成可见晶体，但混合物导致超过 96%的软骨细胞死亡（P<0.001）。
结论：当局部麻醉剂单独应用于细胞或在磷酸盐缓冲盐水稀释溶液中应用时，软骨细胞死亡的比例不到 5%。麻醉剂溶液中的酸度（低至 pH 3.8）或肾上腺素不能解释软骨细胞的死亡。然而，局部麻醉剂与细胞培养基或人滑膜液之间的化学不相容性可能是软骨细胞死亡的原因。
临床相关性：尽管这种用法已经成为一种常见做法，但关节内给予利多卡因和布比卡因并不是这两种麻醉剂的指定用途。医生应该意识到药物和滑液之间的潜在不相容性。
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