An interview with Constance R. Chu, MD

Pain management, particularly after orthopaedic surgery, continues to be an issue for both surgeons and patients. Recent events—including the proliferation of lawsuits following the use of continuous infusion pain pumps after shoulder surgery—have called into question certain pain management practices.

Constance R. Chu, MD, has been studying the effects of local anesthetics on articular chondrocytes for several years. Her latest study, which appeared in the March 2010 issue of The Journal of Bone and Joint Surgery–American, focused on the in vivo effects of a single intra-articular injection of 0.5 percent bupivacaine on articular cartilage. She recently discussed her findings with AAOS Now managing editor Mary Ann Porucznik.

AAOS Now: Your study on the impact of local anesthetics on cartilage has raised some concerns, because the chondral surface remained intact, without visible changes, even though a histologic analysis at 6 months showed a considerable reduction in chondrocyte density. Would you anticipate, then, that a single injection could have a long-term impact, perhaps even leading to the development of osteoarthritis?

Dr. Chu: I think that it’s pretty well accepted that the loss of chondrocytes is a factor in the development of cartilage loss, cartilage degeneration, and eventually osteoarthritis. Certainly we could outline a scenario in which anything that compromises the health of the chondrocytes or leads to loss of cells could potentially have an impact on cartilage tissue loss. But there’s tremendous variability among individuals, so we can’t say that a specific percentage loss would create a definite effect. Our data show that a loss of chondrocytes of 75 percent or more, even in a small animal model, is too much. The cartilage was definitely overwhelmed and broke down over a 6-month period.

AAOS Now: This is a small animal model study, so wouldn’t similar research be needed on large animal models before applying the findings to humans?

Dr. Chu: Certainly a larger animal model would better show the potential effects of a single injection on cartilage that might be more similar to human cartilage.

Small animal models provide pretty good counterparts to laboratory in vitro studies, because they can show whether an observed effect in tissue culture or cell culture actually has a similar effect within a joint. In small animals, arthritic changes can develop rapidly, within weeks to months, facilitating the research. But small animals have thinner tissue, so we do need to have a model—perhaps a goat—that has thicker cartilage, that is considered more similar to humans to better understand the potential effects on human articular cartilage.

One of the downsides of larger animal models, however, is that it may take years for mild-to-moderate chondrocyte injury and loss to progress to observable cartilage damage, which makes it difficult to obtain conclusive results.

AAOS Now: Does the fact that your most recent findings were subclinical have any impact on current practices by orthopaedic surgeons who might administer a single intra-articular injection?

Dr. Chu: I don’t think that orthopaedic surgeons who administer an occasional intra-articular injection need to change their practice patterns. But the value of this study is that it highlights the fact that intra-articular injections of local anesthetics potentially have toxic effects to articular cartilage.

Most therapeutic measures have pluses and minuses. It’s a matter of looking at the clinical situation and trying to minimize the use of the agent. A local anesthetic works by paralyzing the cell membrane. The literature points out that these agents have been known to be toxic to several other cell types. You can use a little bit and get the desired clinical effect of anesthesia, but more isn’t necessarily better and may actually have harmful effects.

With the pain pumps, for example, we don’t know whether the pressure or the anesthetic agent was the problem, but that scenario definitely involves putting a large amount of medication into a small space and continuing to infuse fresh medication. We don’t administer any other medication in that fashion without expecting potentially undesirable other effects.

AAOS Now: Do you use intra-articular injections? If so, when and why?

Dr. Chu: In my practice, I use intra-articular local anesthetics only if I need to. For example, when I’m trying to determine which joint is causing the symptoms, I’ll use a little local anesthetic to numb one of the joints and see if the pain goes away. But for pain after arthroscopy, I’ve found that a portal site injection of a local anesthetic, without going into the joint, is sufficient.

AAOS Now: How much local anesthetic is safe?

Dr. Chu: I don’t think we know yet. I’ve found that even 3 mL in a knee joint can be very effective, but you may have to wait a bit until it circulates through the joint.

I don’t have concerns about using 3 mL to 5 mL in a joint as large as the knee, because the effect is dose- and time-dependent. Our in vitro studies show that, with dilution, the effects virtually go away. A small injection gets diluted fairly rapidly and doesn’t stay in the joint very long.

AAOS Now: What about combining local anesthetics with steroid injections? Do they have a synergistic adverse or protective effect?

Dr. Chu: There actually is a synergistic toxic effect of combining local anesthetic with steroids; we published a study on that in January 2009 in Arthroscopy. We found similar effects in lidocaine, so it’s a class of drugs, not just bupivicaine.

The parallels between this research and research on cortisone injections are very important. Several studies back in the 1960s and 1970s—many performed by Henry J. Mankin, MD—suggested that corticosteroids might have a detrimental effect on the articular cartilage. But we continue to give steroid injections today, because they work so well to relieve the pain of osteoarthritis. But because of Dr. Mankin’s work, physicians are aware of the potential toxic effects on cartilage. A proposal to continuously infuse corticosteroids would have raised a red flag.

To put it in context, the work being done on the toxic effects of local anesthetic on cartilage also raises awareness, as did Dr. Mankin’s research. Physicians shouldn’t be afraid to use local anesthetics if the patient needs them. It’s important, however, that we know that there can be toxic effects.

AAOS Now: What advice would you give to orthopaedic surgeons who might be concerned about the safety of intra-articular injections?

Dr. Chu: It’s not an absolute no; it’s mainly an awareness that intra-articular injections of local anesthetic can, potentially, have toxic effects if too much is used. I would definitely NOT advocate daily injections; they should be spaced out. It’s really the principle of reducing the amount you use to what you really need. We do that with other medications to keep within a “therapeutic window” and only take or use what is needed. The value of the work is that it raises awareness of the potential for negative consequences if you use too much.

Constance R. Chu, MD, is director of the Cartilage Restoration Laboratory at the University of Pittsburgh School of Medicine. Disclosure information—Aircast (DJO); Arthrocare; DePuy, A Johnson & Johnson Company; Smith & Nephew; Stryker; Zimmer. She can be reached at chucr@upmc.edu

Mary Ann Porucznik is managing editor of AAOS Now. She can be reached at porucznik@aaos.org

References:

Chu CR, Coyle CH, Chu CT, Szczodry M, et al. In Vivo Effects of Single Intra-Articular Injection of 0.5% Bupivacaine on Articular Cartilage. J Bone Joint Surg Am, Mar 2010; 92: 599 - 608.

Seshadri V, Coyle CH, Chu CR. Lidocaine Potentiates the Chondrotoxicity of Methylprednisolone. Arthroscopy, April 2009; 25:4: 337-347