Abstract
Single intra-articular (IA) injection of long-acting local anesthetics such as bupivacaine is commonly used clinically for postoperative analgesia, in particular, after arthroscopic surgery. Despite their widespread use, the side effects of IA bupivacaine on joint cartilage as well as hepatotoxic and nephrotoxic effects remain to be elucidated. The aim of this study is to assess the in vitro effect of bupivacaine 5% on donkey chondrocytes at different time points, in addition to the in vivo effects of a single IA bupivacaine injection on the middle carpal joint in a group of 10 clinically healthy adult male donkeys. In phase I, the effect of in vitro treatment with bupivacaine 5% or saline 0.9% on freshly isolated donkey chondrocytes for 30, 60 min, 24, 48, and 96 h was investigated using MTT and LIVE/DEAD assay. In phase II, in vivo effects of single injection of bupivacaine on the middle carpal joint of the donkey were evaluated compared with saline 0.9%. Biochemical analysis of collected serum and synovia was performed. Additionally, articular cartilage damage was evaluated using radiography, computed tomography (CT), catabolic marker expression via quantitative polymerase chain reaction (qPCR), and histopathological examination 96 h after injection. Our results showed that after a 30-min exposure to bupivacaine 5%, the viability of donkey chondrocytes was 97.3 ± 4.4% and was not significantly affected at the indicated time points (n = 8, p < 0.05). No significant changes in biochemical analytes of serum and synovial fluid following IA bupivacaine injection were observed, compared with saline injection (n = 5 for each group, p < 0.05). Furthermore, in vivo IA injection of bupivacaine revealed no significant differences in radiography, CT scan, gene expression of cartilage catabolic biomarkers, and histopathological examination. These results provide an evidence for the safety of bupivacaine on the donkey cartilage.
Highlights
Arthroscopic knee surgery is a commonly performed orthopedic surgery [1, 2]
Saline 0.9% group did not display any cytotoxic effect on donkey chondrocytes
A few cells of donkey chondrocytes were positive to EthD-1 staining after exposure to saline or bupivacaine, as shown in Figure 1B, which shows the cell viability after 4 days of culture, indicating that viability was maintained over time upon culture of cells
Summary
Arthroscopic knee surgery is a commonly performed orthopedic surgery [1, 2]. Postoperative pain and delay of recovery are common consequences of such surgery in humans and animals [3, 4]. Single intra-articular (IA) administration of long-acting local anesthetics is a widely utilized approach for pre- and post-operative analgesia after arthroscopic surgeries due to simplicity and Chondrotoxicity of Single Dose Bupivacaine low economic costs [5]. Despite their extensive use, concerns of chondrotoxicity have been recently raised especially for bupivacaine, levobupivacaine, ropivacaine, mepivacaine, and lidocaine [6,7,8,9]. The authors hypothesized that the lack of chondrotoxicity observed in vivo, compared with that noticed in cell culture [18], might be attributed to dynamic changes of bupivacaine concentrations in joints [17]
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