Chondrolysis After Continuous Intra-Articular Bupivacaine Infusion: An Experimental Model Investigating Chondrotoxicity in the Rabbit Shoulder

Department of Orthopedic Surgery, Rush University Medical Center, Rush Medical College, Chicago, Illinois 60612, USA.
Arthroscopy The Journal of Arthroscopic and Related Surgery (Impact Factor: 3.21). 09/2006; 22(8):813-9. DOI: 10.1016/j.arthro.2006.06.006
Source: PubMed


Postoperative pain pumps are increasingly used to deliver a continuous infusion of local anesthetic into the surgical wound or the joint. Recently, there have been concerns that the use of such devices may be associated with chondrotoxicity and even cases of chondrolysis in the shoulder. An experimental model is presented that investigates potential chondrotoxic effects of a continuous intra-articular infusion of bupivacaine in the rabbit shoulder.
We divided 30 rabbits into 3 groups that received continuous infusions of either saline solution, bupivacaine, or bupivacaine with epinephrine into the glenohumeral joint over a period of 48 hours. Animals were killed after 1 week, and osteochondral and synovial samples from the glenohumeral joint underwent analyses with confocal microscopy for live/dead cell assay, metabolic sulfate uptake assessment, and conventional histologic analysis.
Infusion of bupivacaine with epinephrine and without epinephrine decreased sulfate uptake by 56% (P = .009) and 50% (P = .02), respectively, when compared with saline solution; cell viability decreased by 20% (P = .08) and 32% (P = .02), respectively. Histologic analysis yielded significantly worse scores for bupivacaine infusion with epinephrine (P = .004) and without epinephrine (P = .02). The results for bupivacaine with or without epinephrine were not significantly different.
Continuous intra-articular infusion of bupivacaine with and without epinephrine led to significant histopathologic and metabolic changes in articular cartilage.
Bupivacaine showed profound chondrotoxic effects in an experimental model that closely followed the current clinical application of postoperative pain pumps. The results caution against the use of such devices in applications for smaller joints with minimal clearance or dilution as a result of hematoma, where continuous exposure of cartilage to bupivacaine is expected.

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Available from: James M Williams, Oct 04, 2015
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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.
    Journal of Veterinary Pharmacology and Therapeutics 09/2014; 38(1). DOI:10.1111/jvp.12158 · 1.19 Impact Factor
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    • "However, bupivacaine has been found to be chondrotoxic in vitro and several studies have suggested a dose and time-dependent chondrotoxicity of bupivacaine.15-17 Furthermore, an apparently toxic effect of 0.5% bupivacaine on disc cells and articular chondrocytes in vitro has been reported.18 "
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    ABSTRACT: Purpose Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. Materials and Methods From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. Results Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. Conclusion Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
    Yonsei medical journal 03/2014; 55(2):487-92. DOI:10.3349/ymj.2014.55.2.487 · 1.29 Impact Factor
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    • "Bupivacaine has been found to be chondrotoxic in vitro, and several studies have shown a dose- and time-dependent chondrotoxicity of local anesthetics [6-8]. Furthermore, an effect of 0.5% bupivacaine on disc cells and articular chondrocytes in vitro has been reported [9]. "
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    ABSTRACT: Prospective study of changes in intervertebral disc degeneration after injection of bupivacaine. To examine whether injection of bupivacaine into human intervertebral discs accelerates their degeneration. Bupivacaine is commonly used for therapy and diagnosis of discogenic low back pain. However, several in vitro studies have reported toxic effects of bupivacaine to disc cells. We sought to evaluate whether this finding is clinically relevant. We selected 46 patients with low back pain who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging (MRI) (discography group, n=18), discoblock group (injection of bupivacaine, n=18), and a control group, n=10). There were no significant differences in baseline characteristics across the 3 groups. The two experimental groups underwent either discography or anesthetic discoblock, respectively. All three groups were followed up 5 years after the examination. At 5 years follow-up, there was no significant difference in the rate of disc degeneration among the 3 groups (p>0.1). Moreover, X-ray images showed that there was no significant difference in disc height, range of motion, or translation between flex and extension position (p>0.1). In conclusion, radiologic and MRI findings did not show acceleration of intervertebral disc degeneration at 5 years after a single injection of bupivacaine into human discs.
    Asian spine journal 09/2013; 7(3):212-7. DOI:10.4184/asj.2013.7.3.212
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