In the November 2008 issue of Orthopedics Today, McGowan Institute
faculty member Constance Chu, MD (pictured), the Albert B. Ferguson Jr., MD, Endowed Chair in Orthopaedic Surgery, responded to questions from Douglas Jackson, MD, Chief Medical Editor of the publication, about the effects of local intra-articular anesthesia injections on cartilage. Most orthopaedic surgeons routinely use intra-articular injections of anesthesia in their office practices and following arthroscopic procedures. There is little information available on the potential chondrotoxicity and long-term sequelae of these injections. After reading some of Dr. Chu’s research, Dr. Jackson felt it beneficial for her to share some of her laboratory findings and insight into this subject.
Dr. Chu has studied the effects of commonly used agents for intra-articular injections to include lidocaine, bupivacaine, and the combined effects of lidocaine and Depo-Medrol (methylprednisolone acetate, Pfizer) on articular chondrocytes in vitro. In her research she has found dose- and time-dependent toxic effects of all these agents on articular chondrocytes.
Dr. Chu spoke of her in vitro study examining the viability of human and bovine articular chondrocytes and osteochondral tissues following exposure to bupivacaine. In the study, toxicity was defined by using flow cytometry, time-lapse confocal microscopy, and three-dimensional volumetric imaging to count fluorescently stained live and dead cells at varying time points after exposure to different concentrations of bupivacaine for durations ranging from 15 to 60 minutes.
Several models of exposure were used: intermittent exposure, continuous exposure, and in situ exposure within cartilage with and without intact articular surfaces. Chondrocyte viability following defined exposure was measured using flow cytometry. Time-lapse confocal microscopy was used to quantify chondrocyte death during continuous exposure. Three-dimensional volumetric imaging was used for in situ assessment of chondrocyte viability within articular cartilage after bupivacaine exposure.
Dr. Chu further noted that intra-articular knee injections typically range from 30 cc to 60 cc for local anesthesia before arthroscopic surgery to 5 cc to 10 cc in the office. She considers the 5-cc to 10-cc injections to be low-volume injections and 30-cc to 60-cc injections to be higher-volume injections within a joint with the volume of the knee.
Chondrocyte death can be observed in the laboratory within minutes after exposing articular cartilage to a toxic agent by using appropriate dyes and fluorescent microscopy. Dr. Chu and her team are currently analyzing data from an in vivo study following single injection of potentially chondrotoxic agents.
When asked, “What recommendations regarding the local use of anesthetics do you make to the residents and fellows during discussions at your institution?” Dr. Chu indicated the most important recommendation she has made is to avoid continuous intra-articular infusion of local anesthetics. The in vitro data consistently show a dose and time dependent chondrotoxicity of both bupivacaine and lidocaine suggesting this is a class effect of local anesthetics. By counteracting the dilutional effects of systemic absorption and other joint fluids, continuous intra-articular infusion of local anesthetics can be expected to prolong exposure of chondrocytes to potentially toxic levels of these agents. Eventually, the threshold for chondrolysis may be reached, as has been suggested by clinical reports in the shoulder.
In regards to single injection, her recommendation has been to use the lowest dosage for the shortest period of time to achieve the desired clinical effect. For applications such as impingement test, differential joint injections, or routine office injections for degenerative knees, she has found that 3 cc to 5 cc of 1% lidocaine is sufficient. Minimizing the frequency of single injections of local anesthetics alone or in combination with corticosteroids remains a sound basic principle. For patients who still have articular cartilage, Dr. Chu chose to avoid intra-articular use of agents such as 0.5% bupivacaine for which she has observed severe chondrotoxicity in the laboratory.
Dr. Chu notes that medicine is as much art as science. As such, clinical judgment in weighing the known potential risks and benefits for each situation is most important. Intra-articular local anesthetics have and continue to play an important role in the care of patients with joint pathology.
Dr. Chu is also an Assistant Professor in the Departments of Bioengineering, and Orthopaedic Surgery, University of Pittsburgh, and the Director in the Cartilage Restoration Program in the Department of Orthopaedic Surgery.
Illustration: McGowan Institute for Regenerative Medicine.
American Academy of Orthopaedic Surgeons (06/2008)
Abstract (Journal of Bone and Joint Surgery - British Volume, Vol. 90-B, Issue 6, 814-820)