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Scientific Articles   |    
In Vivo Effects of Single Intra-Articular Injection of 0.5% Bupivacaine on Articular Cartilage
Constance R. Chu, MD1; Christian H. Coyle, PhD1; Charleen T. Chu, MD, PhD1; Michal Szczodry, MD1; Venkat Seshadri, MD1; John C. Karpie, MD1; Kristina M. Cieslak1; Elise K. Pringle, BS1
1 Departments of Orthopaedic Surgery (C.R.C., C.H.C., M.S., V.S., J.C.K., K.M.C., and E.K.P.) and Pathology (C.T.C.), University of Pittsburgh, 200 Lothrop Street, BST E1640, Pittsburgh, PA 15261. E-mail address for C.R. Chu: chucr@upmc.edu. E-mail address for C.H. Coyle: chc54@pitt.edu. E-mail address for C.T. Chu: ctc4@pitt.edu. E-mail address for M. Szczodry: szczodrym@upmc.edu. E-mail address for V. Seshadri: seshadriv@upmc.edu. E-mail address for J.C. Karpie: karpiejc@upmc.edu. E-mail address for K.M. Cieslak: kcieslak@nd.edu. E-mail address for E.K. Pringle: ekp5@pitt.edu
View Disclosures and Other Information
Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Investigation performed at the Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

Copyright ©2010 American Society for Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2010 Mar 01;92(3):599-608. doi: 10.2106/JBJS.I.00425
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Abstract

Background: 

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.

Methods: 

Forty-eight Sprague-Dawley rats received a 100-µL injection of sterile 0.9% saline solution (negative control) into one stifle joint and 100 µL 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.

Results: 

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 = 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.

Conclusions: 

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.

Clinical Relevance: 

This study shows that the in vivo effects of a single injection of intra-articular bupivacaine on articular cartilage are subtle. The data in the monoiodoacetate group show that substantial subsurface pathological effects may not be obvious on gross inspection and suggest that any potential toxic effects of bupivacaine following a single injection would be difficult to detect clinically.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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