In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes
ABSTRACT 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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ABSTRACT: This systematic review provides (1) a synthesis of existing clinical evidence that helps identify factors associated with the development of glenohumeral chondrolysis after arthroscopy (PAGCL), (2) a consolidated conceptualization of potential causal pathways that elucidate proposed mechanisms leading to PAGCL, and (3) a summary of implications for practice, policy, and future research. A computerized literature review using an iterative search process identified 245 publications in English between January 1960 and April 2009. After we applied inclusion and exclusion criteria, 35 articles were stratified into 4 categories of factors related to PAGCL: (1) patient factors, (2) surgical factors (preoperative and intraoperative), (3) postoperative factors, and (4) causal pathways. The majority of studies (61%) focused on surgical factors correlated with PAGCL, and most were laboratory based (n = 21). Publications involving human subjects were descriptive case reports (n = 15), not epidemiologic studies. A total of 88 patients (91 shoulder surgeries) with PAGCL were identified in case reports. The majority of patients (55%) was male, and the mean age was 27.9 years (range, 13.1 to 64 years). Among patients, 68% (n = 53) had implants/anchors, 67% (n = 59) received local anesthetics through a pain pump, and 45% (n = 41) had surgeries involving radiofrequency devices. The causal pathways to PAGCL likely involve initiating and secondary cartilage injury due to mechanical, thermal, or chemical events. The result is a cascade of interactive cellular responses that may include inflammation and chondrocyte apoptosis causing disturbance of cellular metabolism with subsequent loss of the gliding surface, congruity, and synovial fluid, leading to increased friction and accelerated wear that ultimately yield PAGCL. The literature is limited to correlates, rather than true risk factors, for PAGCL. Well-designed epidemiologic studies that examine various exposures in relation to health outcomes, while controlling for potential confounders, are needed to determine relative risks that allow causal inference, thereby facilitating sound practice and policy decision making. Level IV, systematic review.Arthroscopy The Journal of Arthroscopic and Related Surgery 11/2009; 25(11):1329-42. DOI:10.1016/j.arthro.2009.06.001 · 3.19 Impact Factor