Chondrotoxic effects of intra-articular injection of local anaesthetics in the rabbit temporomandibular joint

Single intra-articular injections of local anesthetics are commonly used clinically. Recent in vitro studies have demonstrated chondrotoxic effects of local anesthetics, with the greatest emphasis on bupivacaine toxicity. This in vivo study was conducted to determine whether a single intra-articular injection of 0.5% bupivacaine results in chondrocyte morbidity and rapid chondrolysis. Forty-eight Sprague-Dawley rats received a 100-microL injection of sterile 0.9% saline solution (negative control) into one stifle joint and 100 microL of either preservative-free 0.5% bupivacaine (experimental group) or 0.6 mg/mL monoiodoacetate (positive control) into the contralateral joint. The rats were killed at one week, four weeks, twelve weeks, or six months. Live and dead cells were quantified with use of three-dimensional confocal reconstructions of fluorescent-stained tissues at standardized locations on the distal part of the femur. Histological findings were graded with use of a modified Mankin score, and cell density was quantified with use of custom image-analysis software. In the specimens injected with bupivacaine, the chondral surfaces remained intact as seen with gross and histological examination. No differences in superficial chondrocyte viability or modified Mankin scores were observed between the saline-solution and bupivacaine groups at any location or time point (p > 0.05). Quantitative histological analysis of the bupivacaine-treated knees at six months revealed an up to 50% reduction in chondrocyte density compared with that of the saline-solution-treated knees (p < or = 0.01). Monoiodoacetate injection resulted in death of up to 87% of the superficial chondrocyte cells at one week and chondrolysis at six months. Despite severe histological abnormalities by four weeks after monoiodoacetate injection, cartilage injury was not evident on gross inspection until six months. This in vivo study showing reduced chondrocyte density without cartilage tissue loss six months after a single intra-articular injection of 0.5% bupivacaine suggests bupivacaine toxicity. The effects of bupivacaine were milder than those of an injection of 0.6% monoiodoacetate, which resulted in chondrolysis over the same time period.

Recent basic science studies have demonstrated local anesthetic chondrotoxicity in vivo and in vitro in both human and animal cartilage. Clinically, chondrolysis associated with the use of intra-articular local anesthetic pain pumps has been described by several groups. This has raised concern regarding the clinical use of intra-articular local anesthetics. The authors undertook a review of the current orthopaedic literature on local anesthetic chondrotoxicity and its potential relationship to clinical chondrolysis. Local anesthetics such as bupivacaine, lidocaine, and ropivacaine are chondotroxic to human articular cartilage in vitro, although ropivacaine is less so. The evidence suggests that there is a greater risk for chondrolysis with a longer exposure to a higher concentration of local anesthetic, such as with a pain pump, than with a single injection. However, late cellular and metabolic changes are seen after even a single injection of bupivacaine in animal models, and the loss of an intact cartilage matrix also leads to more extensive chondrocyte death. Some studies suggest that additives and the pH of the local anesthetic solution may also play a role in chondrotoxicity. Intra-articular local anesthetics should be used with caution, especially continuous infusions of bupivacaine and lidocaine at high concentrations in joints with compromised cartilage. The consequences of a single intra-articular injection of local anesthetic remains unclear and requires further investigation. Intra-articular use of local anesthetics may have lasting detrimental effects on human articular cartilage and chondrocytes, although the clinical relationship between local anesthetic exposure and chondrolysis requires further study.

Intraarticular injections of local anesthetics are frequently used as part of multimodal pain regimens. However, recent data suggest that local anesthetics affect chondrocyte viability. In this study, we assessed the chondrotoxic effects of mepivacaine, ropivacaine, and bupivacaine. We hypothesized that specific cytotoxic potencies directly correlate with analgesic potencies, and that cytotoxic effects in intact cartilage are different than in osteoarthritic tissue.