Medication Management in Joint Replacement Surgery

Interviewer: Bret S. Stetka, MD; Interviewee: Susan Goodman, MD

Disclosures

August 14, 2017

Editorial Collaboration

Medscape &

The past decade has seen numerous new drug treatments for rheumatologic disorders, yet the rates of joint replacement procedures have remained relatively stable. As their patients present with increasingly complex medication regimens, clinicians are now faced with the challenge of how to modify perioperative drug treatment regimens. A new set of recommendations developed jointly by the American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) provides guidance on the medical management of patients with rheumatologic conditions who are undergoing joint surgery. Medscape recently spoke with Hospital for Special Surgery rheumatologist Susan Goodman, MD, who was involved in drafting the new guidance.

Susan Goodman, MD

Medscape: Dr Goodman, you were involved in developing new collaborative guidelines between the ACR and the AAHKS.[1] Could you describe the intent of those guidelines and the process of developing them?

Dr Goodman: During the past decade, we have observed that despite the widespread use of drugs, such as biologics, the need for large joint arthroplasty, knee, and hip replacement has not declined significantly in patients with rheumatoid arthritis (RA). Even though patients' quality of life has improved, we continue to see the same proportion of patients coming in for major surgery. This means that the majority of patients coming in for arthroplasty are taking potent immunosuppressants. And if you look at complications of arthroplasty, probably the most worrisome is infection.

In fact, there is an increase in all complications for patients with RA. Looking at this picture, we thought that there could be room to reduce the adverse outcomes related to arthroplasty if we could modify perioperative medication management. We also know that the existing guidelines were quite inconsistent between groups. In fact, if you look at the prescribing activity, even at centers such as ours, it was quite erratic. Some patients would be off their medications for months. Others would not have the medications withheld at all. It was a confused picture overall.

Medscape: When were the earlier guidelines released?

Dr Goodman: The ACR released their recommendations for the use of biologic and disease-modifying drugs in 2008.[2] Those included perioperative use.

Medscape: What was the process like of putting together the guideline committee?

Dr Goodman: The process was really fun. I spoke with the people at the ACR and surgeons at the AAHKS, who had also been thinking along the same lines.

First, we met as what we called the "expert panel," which was a group of orthopedists, rheumatologists, patients, and methodologists, as well as several infectious disease experts. We wanted to define what we could realistically hope to accomplish. We realized that we wanted to address the needs of adults with rheumatic diseases who were taking these medications for RA, psoriatic arthritis, systemic lupus erythematosus, or ankylosing spondylitis and were undergoing elective surgery. We did not think we would address the other complications that may occur with surgery, such as cardiac or thromboembolic complications, because those have been dealt with pretty well by other expert groups. We wanted to focus on antirheumatic therapy.

We met that day and outlined our wish list of things we would like to accomplish in our literature review. We defined a series of questions that looked at what we could expect to accomplish by either continuing or withholding these medications.

Along the way, we found that quite a few of the questions on our wish list were not feasible. Part of the process was also to get feedback from the stakeholder community. ACR and the American College of Orthopaedic Surgeons (ACOS) posted the scope of the intended guidelines.

Once we finalized the project plan, we started an extensive literature review, which was conducted by a separate team. We would speak with that team's leaders by phone every week. On the basis of their findings, the original group of experts met again, weighed the quality of the evidence, and honed in on what we thought we could accomplish. Ultimately, and after many iterations, we ended up with seven recommendations.

The New Recommendations

Medscape: Could you summarize those recommendations?

Dr Goodman: We started by addressing the major group of patients and the major medications, including the synthetic, nonbiologic disease-modifying antirheumatic drugs, such as methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. Our first recommendation was that for patients with RA, psoriatic arthritis, systemic lupus erythematosus, or ankylosing spondylitis, those drugs do not need to be withheld. Indeed, we found some evidence suggesting that infection increased when you withhold these drugs; the inflammatory reaction probably prevents really robust wound healing. We wanted our practitioners to continue those drugs through surgery.

Our second recommendation was to withhold all biologics in these patients. That recommendation was based on indirect evidence because there has never been a randomized controlled trial looking at patients who either continue biologics through surgery or do not. But if you look throughout the literature, there appears to be an increase in infection when biologics are continued. We thought that if we withheld them and gave them the week after the first missed dose and went ahead with the surgery at that point, we would probably minimize the risk for infection. Again, the literature did not provide a good answer to this question, but most of the odds, hazard, and risk ratios show an increase in infection risk with these drugs. Thus, we used the dosing interval, which was probably the most rational way to proceed.

Our third recommendation was to withhold tofacitinib. Tofacitinib is one of the newer medications, and we are seeing an accruing association with infection and this drug. In other words, the risk for infection is increased in patients using tofacitinib.

For the biologics, we decided to use the dosing interval because that appears to reflect the duration of immunosuppression. Tofacitinib, a Janus kinase inhibitor, is given twice daily, but clearly the duration of the immunosuppressing effect is much longer with that. We relied on indirect evidence based on translational data that suggested the host defense returns to normal at 7 days, and we suggested withholding tofacitinib for a full week.

Medscape: And you also looked at patients with lupus?

Dr Goodman: Yes. Our fourth recommendation was for patients with severe lupus. Again, we do not have good data regarding biologics for this group, but we do have indirect evidence from organ transplant patients who are undergoing surgery while taking biologics to prevent rejection. Rituximab is not approved for use in lupus. Golimumab, which is the other biologic used in lupus, is not approved for manifestations of severe lupus.

We decided that for patients with severe lupus, we were better off continuing medications—mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus—through the surgical period. We were concerned that a flare in lupus could be more of a risk to the patient that the risk for infection. Patients with lupus are really a different group from patients with inflammatory arthritis. But we decided that the biologics should be withheld in patients with lupus when they undergo surgery. As a group, we stressed that the patient's treating rheumatologist should become involved with that decision.

The other question concerned patients who did not have severe lupus, and that is recommendation five. In these cases, we believed we could withhold biologics because at the time, the flare would be such that you could easily restart a drug and address the flare if the patients were getting into trouble.

Recommendation six concerns restarting drugs. At 2 weeks, the wound is typically healed, and if there is good evidence of wound healing, no local complications, and no systemic infection—such as urinary tract infections or any of those other issues that can arise after surgery—then the medication could be restarted. If there are any questions about healing, it is very easy to have the patient come in to check the wound.

What About Steroids?

Dr Goodman: Our most controversial recommendation was the seventh, regarding stress-dose steroids. Our recommendation was that if a patient is taking daily steroids for their inflammatory rheumatic disease, there was no need for supraphysiologic glucocorticoid dosing, or stress dosing, but rather they should receive their usual dose of steroids.

We know from other studies that the risk for infection increases with a glucocorticoid dose above 15 mg/day. There have been randomized controlled trials looking at the hemodynamics of patients who received stress-dose steroids versus those who did not, and found that there was no significant difference between those given stress-dose steroids and those receiving their usual daily dose.

Hemodynamic status in patients receiving their usual daily dose of steroids is fine. They generally do not become hypotensive. Those who do become hypotensive usually respond to fluids, as do others undergoing surgery. If a given patient does not respond to fluids, you can always give them additional doses of glucocorticoid for low blood pressure, but it seems that given the risk for infection and the improvement in surgical technique, in terms of stress of surgery, we do not need to routinely expose our patients to this extra load of glucocorticoid on the day of surgery.

Medscape: Why is this recommendation somewhat controversial?

Dr Goodman: Patients who undergo the stress of surgery will excrete less glucocorticoid than patients who have not undergone surgery. But the important endpoint for us is blood pressure and pulse, and those have been fine without stress dosing. Those were not affected.

Early in the 1950s, when no one quite knew what prednisone was and these drugs were being used in patients with rheumatic diseases, the recommendation was made to withhold prednisone for a few days before surgery. Now, withholding steroids turns out to have serious hemodynamic consequences. Back then, surgeries were always done under general anesthesia, and clearly your body does not secrete enough glucocorticoid on its own and there were a couple of cases of severe reactions with a drop in blood pressure in patients who had their prednisone dose withheld for a few days. Again, that was in the 1950s, but according to the literature, physicians assumed that patients needed these high extra doses of glucocorticoid. It turns out that with a better understanding of the physiology, that really is not true, and it probably increases the risk for infection unnecessarily.

Medscape: Have these guidelines been widely implemented yet?

Dr Goodman: Yes; the guidelines are in print and have been presented at the AAHKS meeting, the AAOS meetings, and the ACR. Hopefully, they will be at several other rheumatology and orthopedics meetings.

One other thing we did was to involve a patient panel. When you are dealing with indirect evidence, meaning that no one has conducted randomized controlled trials, it is very important to figure out how patients feel about the the risk for flare versus the risk for infection.

We have also learned that if you include only one or two patients on an expert panel, they often will not feel comfortable arguing and saying that they disagree. Instead, we had a separate panel of patients who examined the same information.

One of the other collaborators and I presented the same data to the panel of 15 patients, and that group voted on the recommendations and helped us determine the strengths and the direction of the recommendations. They were overwhelmingly more concerned about the risk for infection than the risk for disease flares, telling us that they expected the flare when they had surgery. They told us not to be concerned about the flare, but to do the safest thing that could avoid infection.

Because we did not have real clear-cut data, their opinions really helped us put together the guidelines.

Medscape: Have you seen any changes or improvements in outcomes at the Hospital for Special Surgery or nationally as a result of these?

Dr Goodman: It is too soon to see changes at this point, but I will be interested to see whether we can actually get some benefit from this. Infection is infrequent enough that we would not expect to see an immediate change, but hopefully we will.

Medscape: Do you have any final comments?

Dr Goodman: For the most part, we depended on indirect evidence to inform these recommendations. As a result, one of the things we did as a group was to identify a research agenda to firm up the evidence for the guidelines. Thus, the next step will be to continue the collaboration and try to get some firm evidence to answer these questions.

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