In Vitro Exposure to 0.5% Bupivacaine Is Cytotoxic to Bovine Articular Chondrocytes

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Arthroscopy The Journal of Arthroscopic and Related Surgery (Impact Factor: 3.21). 07/2006; 22(7):693-9. DOI: 10.1016/j.arthro.2006.05.006
Source: PubMed


Intra-articular use of 0.5% bupivacaine is common in arthroscopic surgery. This study was conducted to test the hypotheses that (1) 0.5% bupivacaine is toxic to articular chondrocytes, and (2) the intact articular surface protects chondrocytes from the effects of short-term exposure to 0.5% bupivacaine.
Freshly isolated bovine articular chondrocytes were prepared into alginate bead cultures and were treated with 0.5% bupivacaine solution or 0.9% saline for 15, 30 or 60 minutes, washed, and returned to growth media. Chondrocytes were recovered from alginate 1 hour, 1 day, and 1 week after bupivacaine exposure; they were fluorescently labeled to identify apoptotic and dead cells and were analyzed by flow cytometry. Twelve osteochondral cores were harvested from bovine knees. The superficial 1 mm of cartilage was removed from 6 cores (top-off). Intact and top-off cores were submerged in 0.9% saline or 0.5% bupivacaine solution for 30 minutes and then maintained in chondrocyte growth media for 24 hours. Live-cell/dead-cell fluorescent imaging was assessed using confocal microscopy.
Greater than 99% chondrocyte death/apoptosis was observed in all bupivacaine-exposed alginate bead cultures compared with 20% cell death in saline-treated controls (P < .05). Osteochondral cores with intact surfaces treated with 0.5% bupivacaine showed 42% dead chondrocytes. When the articular surface was removed, 0.5% bupivacaine resulted in increased cell death, with 75% dead chondrocytes (P < .05).
Results show that 0.5% bupivacaine solution is cytotoxic to bovine articular chondrocytes and articular cartilage in vitro after only 15 to 30 minutes' exposure. The intact bovine articular surface has some chondroprotective effects.
Because healthy chondrocytes are important for maintenance of the cartilage matrix, chondrocyte loss may contribute to cartilage degeneration. This study shows a cytotoxic effect of 0.5% bupivacaine solution on bovine articular chondrocytes in vitro. Although these results cannot be directly extrapolated to the clinical setting, the data suggest that caution should be exercised in the intra-articular use of 0.5% bupivacaine.

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    • "Several animal-based studies have supported the concept that prolonged exposure to local anesthetics (bupivacaine or lidocaine) damages articular cartilage (Piper et al., 2011; Matsen & Papadonikolakis, 2013). Ex vivo studies suggesting chondrotoxicity have used models in which the bupivacaine concentration is 5 mg/mL (0.5%), and/or in which the bupivacaine exposure is prolonged (e.g. 1 h to 3 days) (Chu et al., 2006; Gomoll et al., 2006; Piper & Kim, 2008; Anz et al., 2009; Bogatch et al., 2010; Dragoo et al., 2010; Hennig et al., 2010). However, the actual local bupivacaine concentration and duration of exposure to chondrocytes after intra-articular injection are unknown. "
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    ABSTRACT: Intra-articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra-articular injection. Eight healthy beagles with normal stifles and 22 large and giant-breed dogs with stifle osteoarthritis (OA) were treated with a single intra-articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra-articular injection.
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    • "Furthermore, we cannot comment on the average time that these chemicals would normally come in contact with IVD cells in clinical situations. However, it has been shown that cell viability after exposure to bupivacaine is greater in intact bovine articular cartilage compared with that of chondrocytes suspended in alginate, suggesting that the natural native matrix structure may provide some protection from local anesthetic exposure [29]. The NP cells from healthy human IVD cells may be less susceptible to anesthetic agents than those from degenerated IVDs. "
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    • "By using an arthroscopic approach, damage to surrounding structures, including the subscapularis, is minimized, resulting in decreased morbidity and rehabilitation required after surgery as compared to standard TSA. idiopathic chondrolysis, rotator cuff arthropathy, or iatrogenic injury [1] [5], which may include the effects of intraarticular pain pumps [6] [7] [8], radiofrequency devices [9] [10] [11] [12], and prominent anchors [13] [14], leading to the phenomenon of post-arthroscopic glenohumeral chondrolysis (PAGCL). Humeral head articular cartilage has a thickness of 1.2–1.3 "
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