In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage.
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-microL injection of sterile 0.9% saline solution (negative control) into one stifle joint and 100 microL 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 < or = 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.
Chu
Constance R
CR
Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, BST E1640, Pittsburgh, PA 15261, USA. chucr@upmc.edu
Coyle
Christian H
CH
Chu
Charleen T
CT
Szczodry
Michal
M
Seshadri
Venkat
V
Karpie
John C
JC
Cieslak
Kristina M
KM
Pringle
Elise K
EK
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects*; D006652:Histological Techniques; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000008:administration & dosage / Q000494:pharmacology; D007719:Knee Joint; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012984:Software; D013194:Staining and Labeling
D000779:Anesthetics, Local; D019807:Iodoacetic Acid; D002045:Bupivacaine