Most of those with rheumatic disease are taking multiple medications, which must be managed during the perioperative period. Currently, the perioperative risks of these medications are not well defined, and there are no recommendations to guide management.7 Up to 3% of the US population is prescribed glucocorticoids as an anti-inflammatory agent. Suppression of the hypothalamopituitary-adrenal axis and the potential risk for adrenal crisis are recognized complications of prolonged glucocorticoid use. 

Additionally, glucocorticoids suppress the normal increase in endogenous cortisol that occurs in response to stress or surgery,8,9 and both cortisol and glucocorticoids are known to delay wound healing. In animal studies, glucocorticoid receptor antagonists have been shown to block glucocorticoid function and eliminate the stress-induced delay in wound healing while preventing glucocorticoid production by means of adrenalectomy.9-11 In addition, bone loss associated with decreased intestinal calcium absorption may be strongly correlated with oral glucocorticoid therapy. 

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The risk for osteoporosis and fracture increase rapidly during glucocorticoid therapy and then decrease rapidly after stopping glucocorticoids.12,13 Exogenous glucocorticoid use has also been linked to increased risk for gastrointestinal perforation, postoperative bleeding, and infection.14,15 Chronic glucocorticoid use can compromise skin integrity both before and after surgical procedures, further complicating surgery and the healing process.2,16 These risks are particularly important in patients with SLE, perhaps because of the multisystem nature of the disease.

The increased bleeding risk associated with glucocorticoids must also be balanced against the risk for bleeding associated with other agents used for pain management, including aspirin and cyclooxygenase-2 (COX-2) inhibitors. In general, aspirin should be discontinued 5 days before any surgical procedure because the antiplatelet effects of aspirin may increase the risk for bleeding. Discontinuation may not be necessary with COX-2 inhibitors, including celecoxib and rofecoxib, because they do not interfere with platelet function. However, COX-2 inhibitors should be used with caution in the perioperative setting because they can inhibit wound healing.17 The rheumatologist must discuss with the surgeon and the anesthesiologist all medications that may have an impact on surgical outcome.

The benefits of nonbiologic and biologic disease-modifying antirheumatic drugs c(DMARDs) have been widely reported in medical literature; however, there are few data to guide the perioperative use of DMARDs.18 Available evidence suggests that methotrexate can be continued during surgery, whereas leflunomide, sulfasalazine, azathioprine, and cyclosporine A should be withdrawn because of their associated increased risk for infection.19 

A prospective, randomized study involving 388 people with RA suggested no increased risk for infection or other postoperative complications resulting from perioperative use of methotrexate, and in fact showed lower rates of reported infection.20,21 In those with renal insufficiency or other surgical complication, withholding methotrexate for 1 week before and 1 week after surgery should be considered, with reinstatement of treatment as soon as the patient is stable.5 Increased infection rates, specifically surgical site infections (SSI), are possibly the greatest perceived risk associated with biologic DMARDs, particularly during postoperative care. 

Evidence regarding the effect of DMARDs on SSIs is mixed. Although some studies have reported higher complication rates with the use of anti-tumor necrosis factor (TNF) agents, other studies have reported no increase in complication rates.21,22 A 2007 study published in the Journal of Rheumatology reported that the strongest risk factor for SSI is history of SSI or skin infection, and the perioperative continuation of anti-TNF agents may not be a relevant risk factor.21 The study also reported that TNF inhibition may impair wound healing, potentially increasing dehiscence, and that interrupting anti-TNF agents may in fact improve wound healing. 

Despite these results, the American College of Rheumatology guidelines recommend discontinuing anti-TNF agents 1 to 4 weeks before surgery.23 Anti-TNF agents may be restarted if there is no evidence of infection and wound healing is satisfactory.23,24 

Until data from well-designed studies on the use of other biologic agents, including abatacept, rituximab, tocilizumab, and tofacitinib, becomes available, it is prudent to follow the recommendations provided for anti-TNF agents.5,19,25 It is necessary to balance the risk for postoperative infection with continued DMARD use against the risk for disease flare and progression when DMARDs are withheld. Furthermore, long-term interruption of anti-TNF therapy may induce the formation of antidrug antibodies and cause subsequent infusion reactions and secondary ineffectiveness.7,21

Total joint arthroplasty, especially in patients with pulmonary hypertension, is considered a risk factor for postoperative venous thromboembolism. Subgroups of patients at elevated risk for venous thromboembolism include those with a high Charlson comorbidity index and those previously hospitalized with cardiovascular or cerebrovascular disease or venous thromboembolism. In general, those with osteoarthritis had a higher risk for postoperative venous thromboembolism than those with RA.26 This finding should allow clinicians to better stratify patients having total hip replacement and target specific thromboprophylaxis modalities.

Summary and clinical applicability

The optimal perioperative management of those with rheumatic diseases begins with careful review of the patient’s clinical condition through history and physical examination, and continues by identifying presenting comorbidities and assessing joint mobility and risks. Collaboration among rheumatologists, anesthesiologists, and orthopedic surgeons is essential for both optimal surgical outcomes and safe perioperative care. 

Moreover, patients with RA or SLE should be assessed for other potential risks. Those taking glucocorticoids or nonbiologic and biologic DMARDs must be assessed carefully prior to surgery, and these agents must be managed appropriately. The immunosuppressive effects of these drugs raise concern for postoperative complications, especially in those undergoing orthopedic surgery, which occurs commonly in those with chronic rheumatologic disease.


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13. Rosen HN. Pathogenesis, clinical features, and evaluation of glucocorticoid-induced osteoporosis. UpToDate. Updated March 12, 2015. Accessed March 23, 2016.

14. Gribsholt SB, Svensson E, Thomsen RW, et al. Preoperative glucocorticoid use and risk of postoperative bleeding and infection after gastric bypass surgery for the treatment of obesity. Surg Obes Relat Dis. 2015;11(6):1212-1217.

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17. Fairweather M, Heit YI, Buie J, et al. Celecoxib inhibits early cutaneous wound healing. J Surg Res. 2015;194(2):717-724.

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23. Goodman SM, Paget S. Perioperative drug safety in patients with rheumatoid arthritis. Rheum Dis Clin North Am. 2012;38(4):747-759.

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26. Pedersen AB, Sorensen HT, Mehnert F, Overgaard S, Johnsen SP. Risk factors for venous thromboembolism in patients undergoing total hip replacement and receiving routine thromboprophylaxis. J Bone Joint Surg Am. 2010;92(12):2156-2164.