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SAN FRANCISCO -- Patients with rheumatoid arthritis (RA) pose heightened and unique surgical risks that mandate careful perioperative and postoperative monitoring, a rheumatologist at one of the world's top orthopedic centers said here.

A fourth of patients with RA require surgery of some type within 20 years of diagnosis. Among patients undergoing total knee or hip replacement, the estimated risk of surgical site infection ranges from two to seven times higher for patients with RA as compared with patients who do not have RA. Some evidence suggests that higher of infection after surgery.

Although the proportion of RA patients requiring joint replacement has decreased dramatically in recent years, the aging of the population means that more patients live longer, increasing the overall odds for surgery.

"It's always been a challenge to us to know how to manage these patients who have unique needs and unique risks," said Sergio Schwartzman, MD, of the Hospital for Special Surgery in New York City, at the California Rheumatology Alliance meeting. "Some of that is referable to the medications used to treat them."

"Some of the cells that are involved in tissue repair, and some of the cytokines that we target in patients with rheumatoid arthritis, are actually necessary for the normal healing process," he added. "If we block these cells and these cytokines, are we incurring a greater risk to our patients in terms of wound healing and the risk for infection?"

The preoperative medical assessment should cover risks common to all surgical patients -- healing and infection, prior experience with anesthesia, bleeding/clotting history, cardiopulmonary, and cerebrovascular -- but also risks specific to RA, including type of surgery, functional status, and medications.

RA confers several types of disease-specific risk, beyond infection and wound healing. For example, 30%-40% of patients with longstanding erosive RA develop cervical instability, and manipulation of the atlanto-axial joint during intubation can , said Schwartzman. Patients should have preoperative cervical spine imaging with flexion and extension views. Patients with cricoarytenoiod joint inflammation and hoarseness should have a consultation with an otolaryngologist.

A cardiovascular evaluation is standard part of the preoperative workup, but patients with RA have a heightened risk of cardiovascular disease, particularly severe disease. Cardiovascular disease is the principal contributor to RA patients' increased mortality risk versus the general population, said Schwartzman, noting that both RA and coronary atherosclerosis have inflammatory etiology and pathogenesis.

Medication Assessment

From the rheumatology perspective, the medication assessment is a distinguishing feature of the perioperative workup for the patient with RA. Considerations include medications that many types of patients use -- such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) -- but also drugs that are much more commonly used by patients with RA, such as biologic agents and disease-modifying antirheumatic drugs (DMARDs).

"The challenge of the medication assessment is to achieve a balance among competing objectives: maintaining disease control, optimizing wound healing, and minimizing perioperative morbidity, especially infections," said Schwartzman.

Scientific wisdom about discontinuing aspirin has turned 180° over the years. Once routinely discontinued to minimize bleeding risks, aspirin is now commonly continued without interruption for surgery. The tide turned in favor of continuing aspirin after a randomized trial showed that patients who continued aspirin during surgery had a significantly lower postoperative risk of .

The data are conflicting regarding non-aspirin NSAIDs, and clinicians can make a case for holding or continuing the drugs, said Schwartzman.

Spinal surgery is a notable exception, as aspirin and non-aspirin NSAIDs are discontinued because NSAIDs can affect bone healing and fusion, and any excess bleeding into the spinal canal carries a risk of paralysis.

Corticosteroids remain a key component treatment for many patients with RA despite being problematic to use. Clinical and preclinical data have shown that long-term corticosteroids can lead to a delay in wound and bone healing and to an increased risk of postoperative complications. The longstanding advice to use the lowest effective dose is as true today as in the past, said Schwartzman.

Two case reports from the early 1950s described unexpected postoperative deaths in patients who had been on chronic steroid therapy, giving rise to the practice of administering a "stress dose" of steroids prior to surgery. Since then, multiple reports have failed to demonstrate clinically meaningful postoperative adrenal insufficiency in patients on chronic steroid therapy, said Schwartzman. Nonetheless, stress dosing remains controversial.

Authors of outlined a rational strategy for managing surgical patients on chronic steroids. The strategy differentiates between major and minor surgery and provides specific dosing recommendations.

"This paper began to raise the issue of not needing stress-dose steroids, and I think it is a strategy that is catching on more and more," said Schwartzman.

After methotrexate became standard of care for RA, contradictory results emerged from retrospective and observational studies regarding the need to discontinue treatment for surgery. Results of a resolved the issue, showing that patients who continued methotrexate had a numerically lower risk of postoperative complications as compared with patients who discontinued the drug or had no history of methotrexate therapy.

Patients who discontinue methotrexate may have disease flare, Schwartzman noted. The drug can be continued safely through surgery with a few notable exceptions: renal impairment, advanced age, liver disease, and possibly diabetes mellitus.

Biologics and DMARDS

With regard to biologic agents used to treat RA, a majority of studies and meta-analyses have shown no increased risk from continuing therapy through surgery, whereas some reports have documented increases in certain types of complications (surgical site infections, deep-vein thrombosis, and delayed healing). Studies have generally showed no increased risk associated with continuation of conventional DMARDs.

Limited data have emerged regarding the safety of continuing rituximab (Rituxan) or tocilizumab (Actemra), and no data exist to guide the decision to continue or discontinue abatacept (Orencia), certolizumab (Cimzia), or golimumab (Simponi), said Schwartzman.

Last year the American College of Rheumatology and the Association of Hip and Knee Surgeons jointly issued a for perioperative management of antirheumatic drugs in patients undergoing hip or knee arthroplasty. The draft included seven recommendations:

• Continue synthetic disease-modifying drugs
• Hold biologics for one dosing cycle before surgery
• Hold tofacitinib (Xeljanz) for 7 days prior to surgery
• Plan surgery for end of dosing cycle for rituximab and belimumab (Benlysta)
• Continue immunosuppressive therapy during surgery for patients with severe systemic lupus erythematosus; hold for 7 days for non-severe disease
• Restart biologics at the onset of wound healing, with sutures out and no sign of infection (about 14 days)
• Continue daily steroids through surgery

"The decision to restart a biologics after surgery should be in the rheumatologist's hands, not the orthopedist's hands," said Schwartzman. "You should make that decision based on your evaluation of the moment."

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