Lidocaine Potentiates the Chondrotoxicity of Methylprednisolone

Seshadri, Venkat; Coyle, Christian H.; Chu, Constance R.

doi:10.1016/j.arthro.2009.01.003

Cited by 84 publications

(61 citation statements)

References 19 publications

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“…However, it is difficult to synthesize these data, because the origin of the investigated chondrocytes, the culture conditions, and the exposure times are distinct. Nevertheless, our data are consistent with that of Seshadri et al [46] who also reported greater cytotoxicity after combined exposure of agents. Other widely used agents for intraarticular osteoarthritis treatment are local anesthetics alleviating pain effectively, yet they may have a cytotoxic action on chondrocytes [7,23,39].…”

Section: Discussionsupporting

confidence: 83%

“…The rationale would be that the local anesthetic component acts quickly after administration, it provides fast alleviation of pain, and it may last for up to the point when the steroid component starts to exert its effect. Although it has been reported that steroids and local anesthetics have a strong cytotoxic effect on chondrocytes, concomitant administration of corticosteroids and local anesthetics in osteoarthritis is still a widely used and investigated method [12,27,32,[45][46][47]. Similar to our findings, a recent study revealed a methylprednisolone-lidocaine combination showed a cytotoxic effect on bovine chondrocytes cultured in alginate beads [46].…”

Section: Discussionsupporting

confidence: 81%

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Increased Chondrocyte Death after Steroid and Local Anesthetic Combination

Farkas

Kvell

Czömpöly

et al. 2010

Clinical Orthopaedics &Amp; Related Research

109

107

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Background Hyaline articular cartilage has limited repair and regeneration capacity. Intraarticular administration of glucocorticoid and local anesthetic injections play an important role in the therapy of osteoarthritis. Glucocorticoids and anesthetics reportedly enhance apoptosis in chondrocytes, but effects of the combined use of glucocorticoids and local anesthetics are unknown. Questions/purposes We asked whether glucocorticoid and local anesthetic agents combined had any synergistic effects on chondrocyte apoptosis. Methods Cell viability and apoptosis/necrosis assessment of human articular chondrocytes were performed in vitro (chondrocyte cell cultures) and ex vivo (osteochondral specimens) using flow cytometry and TUNEL analysis, respectively.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 81%

Increased Chondrocyte Death after Steroid and Local Anesthetic Combination

Farkas

Kvell

Czömpöly

et al. 2010

Clinical Orthopaedics &Amp; Related Research

109

107

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“…The investigators concluded that triamcinolone acetonide attenuated the chondrotoxicity of mepivacaine [5]. In contrast, a study using a bovine cartilage found that, although the methylprednisolone showed time-and dose-dependent chondrotoxic effects, the combination of lidocaine and methylprednisolone showed a synergistic chondrocidal effect; there was no single-treatment lidocaine group for direct comparison to methylprednisolone [41]. In our study on human cartilage, triamcinolone caused a substantial loss of chondrocyte viability in the articular plug and monolayer culture groups and was more chondrotoxic than bupivacaine.…”

Section: Discussionmentioning

confidence: 89%

“…In vitro studies suggest chondrotoxicity of local anesthetics and corticosteroids in various animal models [11,12,22,27,32,41]. However, combinational effects of corticosteroids and local anesthetics or the buffering of these agents have not been studied on human cartilage.…”

Section: Discussionmentioning

confidence: 99%

Bupivacaine and Triamcinolone May Be Toxic To Human Chondrocytes: A Pilot Study

Syed¹,

Green²,

Bianski³

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Intraarticular injections of corticosteroids combined with local anesthetics are commonly used for management of chronic pain symptoms associated with degenerative joint diseases and after arthroscopic procedures. Several studies suggest chondrotoxicity of local anesthetics whereas others report chondroprotective and cytotoxic effects of corticosteroids on cartilage. Given the frequency of use of these agents, it is important to know whether they are in fact toxic. Questions/purposes We asked whether (1) bupivacaine and triamcinolone acetonide, alone and combined, were chondrotoxic to chondrocytes in culture; (2) buffering of the reagents diminished toxicity of the bupivacaine and triamcinolone; and (3) the presence of the superficial layer of articular cartilage protects against toxicity. Materials and Methods We obtained cartilage from three patients undergoing arthroplasty. To address triamcinolone acetonide, bupivacaine, and combinatorial toxicity to human chondrocytes, we set up monolayer chondrocyte cultures (n = 8 wells per condition). The question of buffering was addressed by performing the same assays as above, but the reagents were buffered. An MTT assay was used to assess chondrocyte survival in the monolayer. We harvested 21 articular plugs from each of three patients (total 63 plugs) and exposed them to the same reagents as above, including the buffered reagents. A Live/Dead assay was used to determine chondrocyte survival. Results Triamcinolone acetonide, bupivacaine, and their combination were toxic to human chondrocytes in the monolayer comparisons. The addition of buffering did not mitigate chondrocyte death. With the intact superficial layer in the plug group, bupivacaine was not toxic as compared with for the control group; all the other reagents (triamcinolone, combination bupivacaine/triamcinolone, buffered bupivacaine, buffered triamcinolone, and buffered combination) produced chondrotoxicity. Conclusions Triamcinolone induced chondrotoxicity in the articular plug and monolayer culture, whereas bupivacaine induced chondrotoxicity only in monolayer culture. The combined used of triamcinolone and bupivacaine did not show additive chondrocyte death in any arm. Buffering of bupivacaine increased its chondrotoxicity. Clinical Relevance Although not necessarily reflecting in vivo conditions, our data suggest physicians should be cognizant of the potential in vitro chondrotoxicity of bupivacaine and triamcinolone when contemplating intraarticular administration.

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“…Concerns for systemic toxicity have led to new interest in evaluating the anti-inflammatory effects of high molecular weight hyaluronan 17 . Corticosteroid injections have a known anti-inflammatory effect but many formulations also carry concerns for chondrotoxicity, especially when corticosteroids are combined with local anesthetics 18,19 . While injection therapy reduces the risk of systemic toxicity, long-term and sustained bioactivity remains difficult to achieve without incurring substantial local morbidity from repeated injections.…”

Section: Early Diagnosis Enables Early Treatment To Reduce Osteoarthrmentioning

confidence: 99%

Osteoarthritis: From Palliation to Prevention

Chu

Millis

Olson

2014

The Journal of Bone and Joint Surgery

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Osteoarthritis is a leading cause of disability. The traditional focus on late-stage osteoarthritis has not yielded effective disease-modifying treatments. Consequently, current clinical care focuses on palliation until joint replacement is indicated. A symposium format was used to examine emerging strategies that support the transformation of the clinical approach to osteoarthritis from palliation to prevention. Central to this discussion are concepts for diagnosis and treatment of pre-osteoarthritis, meaning joint conditions that increase the risk of accelerated development of osteoarthritis. The presentation of translational and clinical research on three common orthopaedic conditions-anterior cruciate ligament tear, intra-articular fracture, and hip dysplasia-were used to illustrate these ideas. New information regarding the use of novel quantitative magnetic resonance imaging (MRI) in the form of ultrashort echo time enhanced T2* (UTE-T2*) mapping to evaluate the potential for articular cartilage to heal subsurface damage in a mechanically sound environment was presented. These data indicate that improved diagnostics can both identify cartilage at risk and evaluate the effectiveness of early treatment strategies. With use of a new mouse model for intra-articular fracture, it was shown that inflammation correlated to fracture severity and that super-healer mice avoided early posttraumatic osteoarthritis in part through an enhanced ability to dampen inflammation. These findings suggest that there is a role for acute and sustained anti-inflammatory treatment in the prevention of osteoarthritis. For long-term treatment, contemporary gene-therapy approaches may offer an effective means for sustained intra-articular delivery of anti-inflammatory and other bioactive agents to restore joint homeostasis. To illustrate the potential of early treatment to prevent or delay the onset of disabling osteoarthritis, the positive clinical effects on articular cartilage and in long-term clinical follow-up after operative correction of structural abnormalities about the hip highlight the role for targeting mechanical factors in delaying the onset of osteoarthritis. Given that orthopaedic surgeons treat the full spectrum of joint problems, ranging from joint trauma to preosteoarthritic conditions and end-stage osteoarthritis, an awareness of the paradigm shift toward the prevention of osteoarthritis is critical to the promotion of improved clinical care and participation in clinical research involving new treatment strategies.

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Lidocaine Potentiates the Chondrotoxicity of Methylprednisolone

Abstract: Intra-articular injections of corticosteroids and local anesthetics are widely used in clinical practice. This in vitro study provides information on the potential effects of these drugs on articular cartilage.

Cited by 84 publications

References 19 publications

Increased Chondrocyte Death after Steroid and Local Anesthetic Combination

Increased Chondrocyte Death after Steroid and Local Anesthetic Combination

Bupivacaine and Triamcinolone May Be Toxic To Human Chondrocytes: A Pilot Study

Osteoarthritis: From Palliation to Prevention

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