Department of Orthopaedic Surgery, Stanford University, Palo Alto, California, USA.
Am J Sports Med. 2012 Apr;40(4):794-9. doi: 10.1177/0363546511434571. Epub 2012 Jan 27.
The administration of amide-type local anesthetics to cartilaginous tissues has revealed potential chondrotoxicity.
This study evaluated whether administration of single doses of 1% lidocaine, 0.25% bupivacaine, and 0.5% ropivacaine resulted in decreased chondrocyte viability or cartilage matrix degradation in vitro.
Controlled laboratory study.
Monolayer human chondrocytes and intact cartilage samples were cultured for 1 week in media. Each drug was delivered in a custom bioreactor over its clinical duration of action. A Live/Dead Viability/Cytotoxicity Assay was used to determine the ratio of dead to live cells for monolayer chondrocyte cultures compared with controls. Damage to the cartilage extracellular matrix (ECM) in en bloc cartilage samples was evaluated by analysis of DNA, glycosaminoglycan (GAG), and collagen content.
Chondrocytes treated for 3 hours with a single dose of 1% lidocaine exhibited significantly more cell death (7.9%) compared with control media (2.9%; P < .001). No significant difference in cell death was observed in chondrocytes treated for 6 hours with 0.25% bupivacaine (2.7%) versus controls (2.8%; P = .856) or cells treated for 12 hours in 0.5% ropivacaine (2.9%) versus controls (2.4%; P = .084). There was no significant difference in GAG expression (P = .627) or DNA-normalized GAG expression (P = .065) between the intact cartilage treatment groups; however, the DNA-normalized GAG expression was markedly lower in cartilage cultures treated with 1% lidocaine (3.36 ± 1.15) compared with those in control media (7.61 ± 3.83).
The results of this in vitro study indicate that a single-dose administration of 1% lidocaine resulted in a significant decrease in chondrocyte viability when compared with control cultures.
Single-dose injections of 1% lidocaine may be significantly chondrotoxic, and further investigation regarding in vivo chondrotoxicity appears warranted.
酰胺类局部麻醉药在软骨组织中的应用已显示出潜在的软骨毒性。
本研究评估单次给予 1%利多卡因、0.25%布比卡因和 0.5%罗哌卡因是否会导致体外软骨细胞活力降低或软骨基质降解。
对照实验室研究。
单层人软骨细胞和完整软骨样本在培养基中培养 1 周。每种药物均在定制的生物反应器中以其临床作用时间给药。通过活/死细胞活力/细胞毒性测定法，比较单层软骨细胞培养物与对照的死亡细胞与活细胞的比例。通过分析 DNA、糖胺聚糖 (GAG) 和胶原蛋白含量评估整块软骨样本中软骨细胞外基质 (ECM) 的损伤。
与对照培养基（2.9%；P <.001）相比，用 1%利多卡因单次处理 3 小时的软骨细胞显示出明显更多的细胞死亡（7.9%）。用 0.25%布比卡因处理 6 小时的软骨细胞（2.7%）与对照相比，细胞死亡无显著差异（2.8%；P =.856），用 0.5%罗哌卡因处理 12 小时的细胞（2.9%）与对照相比，细胞死亡也无显著差异（2.4%；P =.084）。完整软骨处理组之间的 GAG 表达（P =.627）或 DNA 归一化 GAG 表达（P =.065）无显著差异；然而，用 1%利多卡因处理的软骨培养物中的 DNA 归一化 GAG 表达明显低于对照培养基（3.36 ± 1.15）（7.61 ± 3.83）。
本体外研究结果表明，与对照培养物相比，单次给予 1%利多卡因可显著降低软骨细胞活力。
单次注射 1%利多卡因可能具有明显的软骨毒性，进一步研究其体内软骨毒性似乎是必要的。
