SLR-March 2014- Eoin Gorman
Reference: Rao; AJ. Johnston; TR. Harris; A. Smith; RL. Costouros; JG. Inhibition of Chondrocyte and Synovial Cell Death After Exposure to Commonly Used Anesthetics: Chondrocyte Apoptosis After Anesthetics. The American Journal of Sports Medicine. 2014 Jan; 42(1): 50-8.
Scientific Literature Review
Reviewed by: Eoin Gorman, DPM
Residency Program: Columbia – St. Mary’s Milwaukee, WI
Podiatric Relevance: With approximately 33 joints in each foot, intra-articular injections by a foot and ankle surgeon is common. Local anesthetics are commonly injected into joints for therapeutic and diagnostic reasons as well as for post-operative pain control. Chondrocyte toxicity is a known complication of exposure to local anesthetics, especially with intra-articular pumps. This study examined chondrocyte as well as synovial cell death after exposure to bupivacaine, lidocaine, ropivacaine and epinephrine, and whether or not cell death could be prevented with a pan-caspase inhibitor. This article supports previous studies that have found chondrocyte death after local anesthetic exposure, provides new evidence showing synovial cell death with local anesthetic exposure, and provides evidence supporting research and development of apoptosis inhibitors for clinical use with local anesthetics.
Methods: The current study exposed in vitro human chondrocytes and synovial cells to environments of 0.5 percent bupivacaine, 1 percent lidocaine, 0.5 percent ropivacaine, and 1:1000 epinephrine for 90 minutes each. In an additional group normal saline was used as a control. An estimate of the percentage of cells undergoing apoptosis was made at one, three, five and seven days using both terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-endlabeling (TUNEL) and immunohistochemistry (caspase-3 Staining). These results were then compared to cells in the same conditions, but treated with an apoptosis inhibiting agent, z-vad-fmk (pan-caspase inhibitor). Results were analyzed by generalized regression models and pairwise confidence intervals.
Results: Chondrocyte apoptosis was found to be highest with 0.5 percent bupivacaine and 1:1000 epinephrine with 60 percent cell death noted. In synovial cells, 1 percent lidocaine induced the greatest amount of apoptosis. Ropivacaine consistently showed the lowest percentage of cell death for both chondrocytes and synovial cells. Local anesthetic exposure was found to cause apoptosis in a time-dependent manner with the greatest effect at five days. When the caspase inhibitor was added, significant reduction in chondrocyte death was noted for all agents with the greatest effect visible with ropivacaine. For synovial cells, apoptosis was significantly reduced by the caspase inhibitor for cells exposed to ropivacaine and lidocaine, with the greatest effect again with ropivacaine.Conclusions: The results of this study confirmed that bupivacaine causes the highest percentage of chondrocyte cell death in vitro compared to lidocaine and ropivacaine. Consistent with other studies, ropivacaine was found to cause the lowest amount of apoptosis. For synovial cells, this study provides the first evidence that local anesthetics can cause apoptosis. Ropivacaine was also found to cause the lowest amount of apoptosis in synovial cells in vitro. The use of a pan-caspase inhibitor resulted in reduction of apoptosis for both chondrocyte and synovial cells with the greatest effect noted with ropivacaine. This study provides evidence that ropivacaine is likely the safest local anesthetic for intra-articular injections. It also provided evidence that apoptosis can be inhibited in chondrocytes and synovial cells with the use of a pan-caspase inhibitor, and may lead to clinical applications in the future.