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Review Article

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Hip Pelvis 2024; 36(4): 250-259

Published online December 1, 2024

https://doi.org/10.5371/hp.2024.36.4.250

© The Korean Hip Society

Perioperative Considerations for Hip Arthroplasty in Patients with Rheumatoid Arthritis

Seung-Chan Kim, MD, PhD , Hyung Chul Park, MD* , Kyung-Hag Lee, MD, PhD†

Author Affiliations
Department of Orthopedic Surgery, Eunpyeong St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea
Department of Orthopedic Surgery, Seoul St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea*
Department of Orthopedic Surgery, National Medical Center, Seoul, Korea†

Correspondence to : Kyung-Hag Lee, MD, PhD https://orcid.org/0000-0001-5734-5542
Department of Orthopedic Surgery, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul 04564, Korea
E-mail: hagine@nmc.or.kr

Seung-Chan Kim and Hyung Chul Park contributed equally to this study as co-first authors.

Received: November 14, 2023; Revised: January 11, 2024; Accepted: January 11, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Due to its distinct features, rheumatoid arthritis (RA), an inflammatory autoimmune disorder, poses challenges in planning for surgical interventions. This review includes available evidence regarding perioperative considerations in management of RA patients, with a focus on hip surgery. RA can affect multiple joints, with development of extra-articular manifestations; therefore, preoperatively, comprehensive medical assessments, including cardiovascular or pulmonary evaluation must be considered in addition to surgical considerations. Modification of medications capable of controlling RA-related disease activity is critical, and requires collaboration with rheumatologists. Surgical considerations include the choice of surgical approach, implant selection, and problems related to weakened soft tissues, fragile bone density, and bony deformity such as protrusio acetabuli. Careful monitoring and more active rehabilitation are recommended for RA patients due to higher risk of postoperative complications. For achievement of optimal outcomes, use of a multidisciplinary perioperative approach is required for patients with RA.

Keywords Rheumatoid arthritis, Autoimmune disease, Perioperative management, Hip surgery, Arthroplasty

INTRODUCTION

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The specific etiology of rheumatoid arthritis (RA), an inflammatory autoimmune disorder primarily affecting bones and joints, has not been determined1). It can manifest as an immune-mediated abnormality leading to bone and joint involvement2). The reported prevalence of RA is approximately 1% of the global population, predominantly impacting females and occurring most commonly during middle age3,4). The pathophysiology of RA is characterized by osteolysis, destruction of articular cartilage, and degradation of synovial tissue; potential involvement of numerous inflammatory cytokines and autoantibodies in these processes has been reported2).

Following onset of RA, joint destruction and erosion of periarticular bone show predominantly symmetrical involvement across almost all joints throughout the body5). Despite the augmented efficacy and impact of therapeutic agents such as disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids, surgical interventions are still considered crucial in treatment of afflicted joints in patients with advanced RA6,7). In contrast to the general population, various systemic attributes of these patients as well as numerous risk factors can influence poor post-surgical prognoses8,9). Therefore, when planning for lower extremity surgery, orthopedic surgeons should consider the distinctive complexities associated with RA patients throughout the phases of preoperative, intraoperative, and postoperative preparation, with the goal of optimizing favorable surgical outcomes and the overall quality of life for patients.

PREOPERATIVE MEDICAL ASSESSMENT

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RA is a condition characterized by chronic systemic inflammation. According to recent studies, the likelihood of developing cardiovascular issues such as venous thromboembolism (VTE), myocardial infarction, atherosclerosis, congestive heart failure, and stroke, is increased by more than 50% for RA patients when compared with the general population10). Pulmonary complications, which account for approximately 10%-20% of RA-associated deaths, should also be considered11). RA can affect the pleura, vasculature, parenchyma, and airway of the lungs, potentially leading to development of interstitial lung disease, which can be fatal12). Due to the lack of a clear consensus on perioperative management in this regard, consultation with a pulmonologist is recommended for proper management13). Anemia, which is frequently observed in RA patients, is primarily attributed to chronic illness. The postoperative transfusion requirements may be higher for total joint arthroplasty procedures involving knee or hip joints with significant blood loss than in typical cases14). Therefore, preoperative use of erythropoietin and iron supplements is recommended14). In this context, a study examining risk factors for transfusion risk reported that a history of preoperative transfusions, prior total hip arthroplasty (THA), and a history of myocardial infarction were predictive risk factors for postoperative transfusion15).

PREOPERATIVE PHARMACOLOGIC MANAGEMENT AND MODIFICATION

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Recent advancements in antirheumatic therapy have led to remarkable progress in the treatment of rheumatic musculoskeletal diseases. The advent of DMARDs has resulted in significantly enhanced patient survival and reduced the necessity for orthopedic interventions. In addition, use of other immunosuppressive medications such as glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) has led to significantly enhanced quality of life for patients with RA6,16,17). However, even with optimal medical treatment, surgical intervention is still required for some patients due to damage caused by deteriorating joints7). While they are essential for treating RA through suppression of immune function, the risk of postoperative complications may be increased in some cases, therefore, modification of these medications before and after surgery is critical18).

1. DMARDs

A variety of DMARDs and biologic agents can be employed for regulation of disease activity in patients with RA or other inflammatory diseases19). DMARDs commonly used in the treatment of RA include methotrexate (MTX), leflunomide (Arava®), sulfasalazine, hydroxychloroquine, and doxycycline. Biologic agents include adalimumab (Humira®), infliximab (Remicade®), etanercept (Enbrel®), golimumab (Simponi®), rituximab (Rituxan®), abatacept (Orencia®), tocilizumab (Actemra®), anakinra (Kineret®), certolizumab (Cimzia®), secukinumab (Cosentyx®), ustekinumab (Stelara®), and tofacitinib (Xeljanz®), as well as others. These medications are sometimes discontinued before surgery to reduce the risk of infection, which could induce RA flares before and after surgery, potentially impeding postoperative rehabilitation17). The 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons (ACR/AAHKS) Guidelines provide reference criteria for the discontinuation of these medications prior to surgery and the timing of their resumption postoperatively (Table 1)20).

Table 1 . Recommended Perioperative Modification of RA Medications according to the 2022 ACR/AAHKS Guideline

MedicationDosing intervalRecommended time for when the surgery is possible since last administration
DMARDs: Not stop through surgery
MTXWeeklyAnytime
SulfasalazineOnce or twice dailyAnytime
HydroxychloroquineOnce or twice dailyAnytime
Leflunomide (Arava®)DailyAnytime
DoxycyclineDailyAnytime
Biologic agents: Stop through surgery (In the absence of systemic infections, surgical site infection or wound healing problem, restart at minimum 14 days after surgery)
Infliximab (Remicade®)Every 4, 6, or 8 weeksWeek 5, 7, or 9
Adalimumab (Humira®)Weekly or every 2 weeksWeek 2 or 3
Etanercept (Enbrel®)Weekly or twice weeklyWeek 2
Golimumab (Simponi®)Every 4 weeks (subcutaneous)
or every 8 weeks (intravenous)		Week 5
Week 9
Abatacept (Orencia®)Monthly (intravenous)
or weekly (subcutaneous)		Week 5
Week 2
Certolizumab (Cimzia®)Every 2 or 4 weeksWeek 3 or 5
Rituximab (Rituxan®)2 doses 2 weeks apart every 4-6 monthsMonth 7
Tocilizumab (Actemra®)Every week (subcutaneous)
or every 4 weeks (intravenous)		Week 2
Week 5
Anakinra (Kineret®)DailyDay 2
IL-17 secukinumab (Cosentyx®)Every 4 weeksWeek 5
Ustekinumab (Stelara®)Every 12 weeksWeek 13
Ixekizumab (Taltz®)Every 4 weeksWeek 5
IL-23 guselkumab (Tremfya®)Every 8 weeksWeek 9
JAK inhibitor: Stop 3 days before surgery
Tofacitinib (Xeljanz®)Daily or twice dailyDay 4
Baricitinib (Olumiant®)DailyDay 4
Upadacitinib (Rinvoq®)DailyDay 4

RA: rheumatoid arthritis, ACR/AAHKS; American College of Rheumatology/American Association of Hip and Knee Surgeons, DMARDs: disease-modifying antirheumatic drugs, MTX: methotrexate, IL: interleukin.

MTX is the most commonly used medication in the treatment of RA21). It functions as a cytotoxic agent, which can improve symptoms and prevent joint destruction by suppressing production of cytokines, increasing adenosine release, inhibiting immune cell proliferation, and inducing cell apoptosis21,22). Some studies have reported that use of MTX before and after orthopedic surgery did not result in increased infection or complication risks in both short-term and long-term follow-up23-25). However, inflammatory flare-ups are a potential complication of discontinuing MTX26). Based on these findings, discontinuing MTX may not be necessary for patients whose disease activity is well-controlled with MTX therapy25). When using MTX as a treatment for RA, MTX toxicity may be a possibility in cases involving elderly patients or those with impaired renal or hepatic function that may affect drug metabolism25). In such cases, discontinuation of MTX is recommended for one week prior to surgery and one to two weeks following surgery. The risk of flare-ups may be increased with prolonged suppression of MTX for more than four weeks27).

Leflunomide inhibits synthesis of pyrimidine28). According to recent reports, the risk of surgical wound infection was not increased with use of leflunomide therapy29), and the 2022 ACR/AAHKS Guidelines recommend continuing leflunomide therapy both before and after surgery20,30).

Immune responses are mediated by tumor necrosis factor (TNF)-α, a macrophage-derived cytokine, which is also involved in joint destruction in RA patients31,32). Inhibitors of TNF-α such as infliximab, etanercept, and adalimumab are commonly employed for regulating the activity of RA, but can increase the risk of opportunistic infections due to immune suppression33). Some reports have suggested a tenfold increase in the risk of infection when preoperative TNF-α inhibitors are taken concomitantly or separately with conventional DMARDs34). 2022 ACR/AAHKS Guidelines recommend discontinuing such medications before surgery, and scheduling surgery at the end of the dosing cycle20,30). Resumption of TNF-α inhibitors approximately 14 days postoperatively is recommended in cases without wound healing issues, surgical site infections, or systemic infections. However, immediate resumption of TNF-α inhibitors is recommended if there are clinical indications of postoperative RA flare-ups without evidence of infection20,30,35).

2. Steroids

Glucocorticoids, which are commonly used in management of RA patients, enable a more rapid onset of action and the potential for rapid improvement of symptoms compared to DMARDs16). However, sustained use of glucocorticoids can lead to a compromised immune system, reduced bone mineral density, and delayed wound healing36). Long-term consumption of glucocorticoids by RA patients can lead to suppression of the hypothalamic-pituitary-adrenal axis, resulting in decreased secretion of corticotropin-releasing hormone and steroidogenic enzymes from the adrenal glands37). This inhibition can lead to reduced secretion of postoperative cortisol and increased potential for development of adrenal insufficiency37). The benefit of administering a physiological dose of glucocorticoids, which is subsequently tapered gradually to preoperative levels, in reducing the risk of these complications has been demonstrated37). Tailoring the dose of glucocorticoids for each patient is critical to obtaining balance between preventing adrenal insufficiency or Addisonian crisis and preventing delay of wound healing and infection37,38). When possible, a patient considered fit to undergo elective THA would be prescribed a daily dose of prednisone or its equivalent that is less than 20 mg39,40).

3. NSAIDs

NSAIDs are commonly used as adjuvants in the treatment of RA and are often used in conjunction with DMARDs41). Aspirin is a commonly used NSAID that primarily targets cyclooxygenase (COX)-1 by irreversibly inhibiting its function. This action plays a role in inhibition of platelet function and thrombosis42,43). Because the action of aspirin is irreversible, the turnover rate of COX rather than the half-life of the drug should be considered in perioperative management44). Platelets have a lifespan of approximately 8 to 10 days, with a turnover rate of 10% per day45). However, hemostasis could occur in normal platelets with 20% of COX-1 activity, achievable within 72 hours46). Therefore, aspirin should be discontinued 72 hours before surgery, and to minimize postoperative risk of bleeding, it can be resumed 8 to 10 days afterward47). Other NSAIDs function as reversible competitive inhibitors to both COX-1 and COX-2, and the dosage and half-life of each medication should be considered when making perioperative drug adjustments44).

Continued use of aspirin without discontinuation is recommended in certain situations48). Recent studies have reported minimal differences in terms of myocardial infarctions or VTE between groups taking aspirin and placebo49). However, maintenance of aspirin therapy without discontinuation is recommended in cases of preexisting cardiovascular disease50).

PREOPERATIVE SURGICAL CONSIDERATIONS

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Debate between rheumatologists and orthopedic surgeons regarding the appropriate timing for surgical intervention is ongoing51). Earlier orthopedic surgical intervention is recommended in cases of advanced joint damage due to treatment limitations resulting from significant progression of joint destruction and the acknowledged influence of preoperative joint function on postoperative outcomes52). Conventionally, lower extremities are usually prioritized over upper extremities, with sequential surgery performed on the foot, hip, knee, hindfoot, and ankle38). When arthroplasty is indicated for both knee and hip joints, prioritizing THA prior to total knee arthroplasty can be beneficial38). Prioritizing THA can enable appropriate femoral alignment and length of the lower extremity, as well as achievement of optimal knee flexion due to its capacity to enhance hip joint range of motion53). Cervical spine involvement, which is common in patients with RA, can cause instability, including subaxial instability and basilar invagination54). Hyperextension of the neck is required during intubation under general anesthesia, which can pose a risk in cases of instability. Therefore, assessment of preoperative anteroposterior, lateral cervical plain, flexion and extension radiographs is important41). Regional anesthesia may be necessary in some cases involving instability53). In addition, when general anesthesia is required, fiberoptic intubation may be a suitable anesthetic modality53). Although rare, in severe cases of cervical instability, surgical treatment on the cervical spine may be required before undergoing surgery on the lower extremity to prevent further destruction of the cervical spine or neurological injuries55).

INTRAOPERATIVE SURGICAL CONSIDERATIONS

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1. Surgical Approach

While there is no previous research providing clear guidance on the most suitable approach for management of RA patients, the merits of each approach and the surgeon’s preference should be considered when deciding on the surgical approach. The commonly used posterolateral approach enables exceptional visibility of both acetabulum and femur without disrupting the hip abductor muscles by splitting the gluteus maximus muscles to reach the hip joint posteriorly56). By contrast, use of the anterior approach may cause less damage and may be advantageous in management of deformities in hip flexion or external rotation, necessitating removal of the anterior joint capsule57). The findings of a recent retrospective study comparing the correlation between surgical approaches and complications in adults indicated an association of the anterior approach with increased risk of complications including deep infection necessitating surgery, dislocation, and revision arthroplasty compared to the posterior or lateral approaches within one year58). In addition, a trochanteric osteotomy can be initially attempted in cases involving a severe acetabular protrusion deformity that hinders hip dislocation59). In more challenging cases, the Modified Trochanteric Slide Osteotomy technique may be employed to facilitate dislocation with use of the posterolateral or posterior approach60).

Given the rich vascularization of the synovial membrane in RA patients, close attention is required during complete removal of the hypertrophic synovium to minimize excessive bleeding60). Administration of tranexamic acid via intravenous or intra-articular routes is recommended to reduce intraoperative bleeding14).

Characteristics of patients with RA include weakened soft tissues and bone density53). Therefore, soft tissues should be handled with care, and skin damage should be avoided when applying skin retractors. Considering bone density, cortical and cancellous bone can become fragile, potentially leading to bone damage caused by use of traction devices during surgery, perforation of the intramedullary canal, and femoral fractures61). Use of a blunt guide and reaming with an image amplifier is recommended as a preventive measure. Intraoperative femoral fractures usually occur during hip dislocation, thus, when failure of hip dislocation occurs first, neck cutting should be performed prior to dislocation.

2. Implant Selection

Regarding the implants used during surgery, no significant difference associated with use of cement has been reported62). However, recent trends have favored cementless implants62). Arguments in support of using cement typically involve osteoporosis and a wide femoral canal63). A femoral canal can be excessively large, therefore, caution is warranted when using cementless femoral stems64), and in cases of juvenile RA, femoral canals may be too narrow and deformed, potentially necessitating the use of custom-made stems or modular components65).

In THA for patients with RA, hip dislocations are more common in RA patients66). This is often attributed to the use of smaller femoral heads in RA patients, resulting in a short jump distance, loose soft tissues, and poor abductor strength67,68). To minimize dislocations, verifying the anatomical position of the hip center is critical69). Some studies have suggested the use of constrained implants; however, considering the poor bone quality observed in RA patients, use of dual mobility constructs, which have been increasingly used in recent years, may be beneficial70), because similar clinical outcomes can be achieved with use of dual mobility constructs compared to fixed-bearing constructs in performance of THA surgery71).

3. Other Considerations When Planning an Acetabular Procedure

Preparing the acetabulum during performance of THA can be divided into two primary processes: preparation of the acetabular ring and preparation of the acetabular floor. For preparation of the acetabular ring, reamers that are approximately 1-2 sizes smaller than the actual cup size that will be used should be selected. However, for preparation of the acetabular floor, caution is required due to the risk of perforation72). In this case, curettes can be used for selective removal of soft tissues, while perforation of hardened areas can be performed using K-wires to facilitate bleeding.

Protrusio acetabuli, which has been reported in approximately 15%-20% of RA patients, shows slow progression at a rate of 2-3 mm per year73). However, in some cases, rapid progression can lead to rapid worsening of symptoms, requiring specialized attention74). In addition, failure to address protrusio acetabuli, a condition involving contact of the lesser trochanter with the acetabulum, can significantly complicate surgical procedures when performing THA. Bone grafting and use of a standard cup are usually sufficient for milder cases of protrusio acetabuli74). Lee et al.75) also reported that although restoration of the hip center was not achieved in cases with mild protrusio acetabuli, press-fitted cups showed appropriate initial stability and favorable clinical results were obtained. However, in cases with medial wall damage, various plates and rings can be used, and cemented techniques may also be considered74). Although tantalum acetabular cups may be a suitable option, no evidence to support their use in RA patients has been reported74).

4. Others

For RA patients, common complications after hip surgery include infection and wound-related problems76). To avoid such complications, careful hemostasis is required to prevent formation of hematomas. Use of drainage for a specific period after surgery is recommended76). When closing skin, manipulation of soft tissues can be a cause of skin necrosis, blister formation, and secondary infections, which can adversely affect wound healing, and should therefore be minimized, particularly in cases with excessive tension76).

POSTOPERATIVE OUTCOMES AND MANAGEMENT

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Close monitoring after surgery is necessary to reduce the risk of complications, particularly for longstanding RA patients77). Patient education is also an important factor in the effort to minimize postoperative complications78). According to a recent systematic review and meta-analysis, the complication rates subsequent to THA for RA patients were higher for hip dislocation, periprosthetic joint infection, wound healing problems, and periprosthetic fracture when compared with osteoarthritis patients66).

Acute flare within six weeks after surgery has been reported in 63% of patients with RA79). However, the reported percentage of patients seeking medical help was 4%, thus education regarding postoperative flare should be provided79). Reassurance is important for these patients as no association with a flare after one year following surgery has been reported80-82).

Concurrent joint pain and deformities should be considered when planning for rehabilitation after surgery. Patients with active RA generally show delayed functional improvement and have longer hospital stays than patients with other conditions83). Therefore, early mobilization and physiotherapy immediately after hip surgery is required for RA patients to prevent immobilization related complications and joint contractures83). In addition, a multi-disciplinary approach should be applied postoperatively, particularly when restarting DMARDs and other RA medications76).

SUMMARY

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When performing hip surgery in RA patients, a comprehensive perioperative assessment is essential to achieving favorable outcomes. Medications administered for controlling the activity of RA should be adjusted in cooperation with rheumatologists. In addition, considering the extended duration of RA, preoperative assessment of cardiovascular and pulmonary function, anemia, and the cervical spine is necessary. Considering the unique characteristics of RA patients, factors including soft tissue and bony preparation, as well as implant selection during surgery should be considered. The risk of postoperative complications is higher for RA patients compared to the general population, thus close monitoring is important, and more proactive rehabilitation may be required for recovery.

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Article

Review Article

Hip Pelvis 2024; 36(4): 250-259

Published online December 1, 2024 https://doi.org/10.5371/hp.2024.36.4.250

Copyright © The Korean Hip Society.

Perioperative Considerations for Hip Arthroplasty in Patients with Rheumatoid Arthritis

Seung-Chan Kim, MD, PhD , Hyung Chul Park, MD* , Kyung-Hag Lee, MD, PhD†

Department of Orthopedic Surgery, Eunpyeong St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea
Department of Orthopedic Surgery, Seoul St. Mary’s Hospital, School of Medicine, The Catholic University of Korea, Seoul, Korea*
Department of Orthopedic Surgery, National Medical Center, Seoul, Korea†

Correspondence to:Kyung-Hag Lee, MD, PhD https://orcid.org/0000-0001-5734-5542
Department of Orthopedic Surgery, National Medical Center, 245 Eulji-ro, Jung-gu, Seoul 04564, Korea
E-mail: hagine@nmc.or.kr

Seung-Chan Kim and Hyung Chul Park contributed equally to this study as co-first authors.

Received: November 14, 2023; Revised: January 11, 2024; Accepted: January 11, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Due to its distinct features, rheumatoid arthritis (RA), an inflammatory autoimmune disorder, poses challenges in planning for surgical interventions. This review includes available evidence regarding perioperative considerations in management of RA patients, with a focus on hip surgery. RA can affect multiple joints, with development of extra-articular manifestations; therefore, preoperatively, comprehensive medical assessments, including cardiovascular or pulmonary evaluation must be considered in addition to surgical considerations. Modification of medications capable of controlling RA-related disease activity is critical, and requires collaboration with rheumatologists. Surgical considerations include the choice of surgical approach, implant selection, and problems related to weakened soft tissues, fragile bone density, and bony deformity such as protrusio acetabuli. Careful monitoring and more active rehabilitation are recommended for RA patients due to higher risk of postoperative complications. For achievement of optimal outcomes, use of a multidisciplinary perioperative approach is required for patients with RA.

Keywords: Rheumatoid arthritis, Autoimmune disease, Perioperative management, Hip surgery, Arthroplasty

INTRODUCTION

The specific etiology of rheumatoid arthritis (RA), an inflammatory autoimmune disorder primarily affecting bones and joints, has not been determined1). It can manifest as an immune-mediated abnormality leading to bone and joint involvement2). The reported prevalence of RA is approximately 1% of the global population, predominantly impacting females and occurring most commonly during middle age3,4). The pathophysiology of RA is characterized by osteolysis, destruction of articular cartilage, and degradation of synovial tissue; potential involvement of numerous inflammatory cytokines and autoantibodies in these processes has been reported2).

Following onset of RA, joint destruction and erosion of periarticular bone show predominantly symmetrical involvement across almost all joints throughout the body5). Despite the augmented efficacy and impact of therapeutic agents such as disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids, surgical interventions are still considered crucial in treatment of afflicted joints in patients with advanced RA6,7). In contrast to the general population, various systemic attributes of these patients as well as numerous risk factors can influence poor post-surgical prognoses8,9). Therefore, when planning for lower extremity surgery, orthopedic surgeons should consider the distinctive complexities associated with RA patients throughout the phases of preoperative, intraoperative, and postoperative preparation, with the goal of optimizing favorable surgical outcomes and the overall quality of life for patients.

PREOPERATIVE MEDICAL ASSESSMENT

RA is a condition characterized by chronic systemic inflammation. According to recent studies, the likelihood of developing cardiovascular issues such as venous thromboembolism (VTE), myocardial infarction, atherosclerosis, congestive heart failure, and stroke, is increased by more than 50% for RA patients when compared with the general population10). Pulmonary complications, which account for approximately 10%-20% of RA-associated deaths, should also be considered11). RA can affect the pleura, vasculature, parenchyma, and airway of the lungs, potentially leading to development of interstitial lung disease, which can be fatal12). Due to the lack of a clear consensus on perioperative management in this regard, consultation with a pulmonologist is recommended for proper management13). Anemia, which is frequently observed in RA patients, is primarily attributed to chronic illness. The postoperative transfusion requirements may be higher for total joint arthroplasty procedures involving knee or hip joints with significant blood loss than in typical cases14). Therefore, preoperative use of erythropoietin and iron supplements is recommended14). In this context, a study examining risk factors for transfusion risk reported that a history of preoperative transfusions, prior total hip arthroplasty (THA), and a history of myocardial infarction were predictive risk factors for postoperative transfusion15).

PREOPERATIVE PHARMACOLOGIC MANAGEMENT AND MODIFICATION

Recent advancements in antirheumatic therapy have led to remarkable progress in the treatment of rheumatic musculoskeletal diseases. The advent of DMARDs has resulted in significantly enhanced patient survival and reduced the necessity for orthopedic interventions. In addition, use of other immunosuppressive medications such as glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) has led to significantly enhanced quality of life for patients with RA6,16,17). However, even with optimal medical treatment, surgical intervention is still required for some patients due to damage caused by deteriorating joints7). While they are essential for treating RA through suppression of immune function, the risk of postoperative complications may be increased in some cases, therefore, modification of these medications before and after surgery is critical18).

1. DMARDs

A variety of DMARDs and biologic agents can be employed for regulation of disease activity in patients with RA or other inflammatory diseases19). DMARDs commonly used in the treatment of RA include methotrexate (MTX), leflunomide (Arava®), sulfasalazine, hydroxychloroquine, and doxycycline. Biologic agents include adalimumab (Humira®), infliximab (Remicade®), etanercept (Enbrel®), golimumab (Simponi®), rituximab (Rituxan®), abatacept (Orencia®), tocilizumab (Actemra®), anakinra (Kineret®), certolizumab (Cimzia®), secukinumab (Cosentyx®), ustekinumab (Stelara®), and tofacitinib (Xeljanz®), as well as others. These medications are sometimes discontinued before surgery to reduce the risk of infection, which could induce RA flares before and after surgery, potentially impeding postoperative rehabilitation17). The 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons (ACR/AAHKS) Guidelines provide reference criteria for the discontinuation of these medications prior to surgery and the timing of their resumption postoperatively (Table 1)20).

Table 1 . Recommended Perioperative Modification of RA Medications according to the 2022 ACR/AAHKS Guideline.

MedicationDosing intervalRecommended time for when the surgery is possible since last administration
DMARDs: Not stop through surgery
MTXWeeklyAnytime
SulfasalazineOnce or twice dailyAnytime
HydroxychloroquineOnce or twice dailyAnytime
Leflunomide (Arava®)DailyAnytime
DoxycyclineDailyAnytime
Biologic agents: Stop through surgery (In the absence of systemic infections, surgical site infection or wound healing problem, restart at minimum 14 days after surgery)
Infliximab (Remicade®)Every 4, 6, or 8 weeksWeek 5, 7, or 9
Adalimumab (Humira®)Weekly or every 2 weeksWeek 2 or 3
Etanercept (Enbrel®)Weekly or twice weeklyWeek 2
Golimumab (Simponi®)Every 4 weeks (subcutaneous)
or every 8 weeks (intravenous)		Week 5
Week 9
Abatacept (Orencia®)Monthly (intravenous)
or weekly (subcutaneous)		Week 5
Week 2
Certolizumab (Cimzia®)Every 2 or 4 weeksWeek 3 or 5
Rituximab (Rituxan®)2 doses 2 weeks apart every 4-6 monthsMonth 7
Tocilizumab (Actemra®)Every week (subcutaneous)
or every 4 weeks (intravenous)		Week 2
Week 5
Anakinra (Kineret®)DailyDay 2
IL-17 secukinumab (Cosentyx®)Every 4 weeksWeek 5
Ustekinumab (Stelara®)Every 12 weeksWeek 13
Ixekizumab (Taltz®)Every 4 weeksWeek 5
IL-23 guselkumab (Tremfya®)Every 8 weeksWeek 9
JAK inhibitor: Stop 3 days before surgery
Tofacitinib (Xeljanz®)Daily or twice dailyDay 4
Baricitinib (Olumiant®)DailyDay 4
Upadacitinib (Rinvoq®)DailyDay 4

RA: rheumatoid arthritis, ACR/AAHKS; American College of Rheumatology/American Association of Hip and Knee Surgeons, DMARDs: disease-modifying antirheumatic drugs, MTX: methotrexate, IL: interleukin..

MTX is the most commonly used medication in the treatment of RA21). It functions as a cytotoxic agent, which can improve symptoms and prevent joint destruction by suppressing production of cytokines, increasing adenosine release, inhibiting immune cell proliferation, and inducing cell apoptosis21,22). Some studies have reported that use of MTX before and after orthopedic surgery did not result in increased infection or complication risks in both short-term and long-term follow-up23-25). However, inflammatory flare-ups are a potential complication of discontinuing MTX26). Based on these findings, discontinuing MTX may not be necessary for patients whose disease activity is well-controlled with MTX therapy25). When using MTX as a treatment for RA, MTX toxicity may be a possibility in cases involving elderly patients or those with impaired renal or hepatic function that may affect drug metabolism25). In such cases, discontinuation of MTX is recommended for one week prior to surgery and one to two weeks following surgery. The risk of flare-ups may be increased with prolonged suppression of MTX for more than four weeks27).

Leflunomide inhibits synthesis of pyrimidine28). According to recent reports, the risk of surgical wound infection was not increased with use of leflunomide therapy29), and the 2022 ACR/AAHKS Guidelines recommend continuing leflunomide therapy both before and after surgery20,30).

Immune responses are mediated by tumor necrosis factor (TNF)-α, a macrophage-derived cytokine, which is also involved in joint destruction in RA patients31,32). Inhibitors of TNF-α such as infliximab, etanercept, and adalimumab are commonly employed for regulating the activity of RA, but can increase the risk of opportunistic infections due to immune suppression33). Some reports have suggested a tenfold increase in the risk of infection when preoperative TNF-α inhibitors are taken concomitantly or separately with conventional DMARDs34). 2022 ACR/AAHKS Guidelines recommend discontinuing such medications before surgery, and scheduling surgery at the end of the dosing cycle20,30). Resumption of TNF-α inhibitors approximately 14 days postoperatively is recommended in cases without wound healing issues, surgical site infections, or systemic infections. However, immediate resumption of TNF-α inhibitors is recommended if there are clinical indications of postoperative RA flare-ups without evidence of infection20,30,35).

2. Steroids

Glucocorticoids, which are commonly used in management of RA patients, enable a more rapid onset of action and the potential for rapid improvement of symptoms compared to DMARDs16). However, sustained use of glucocorticoids can lead to a compromised immune system, reduced bone mineral density, and delayed wound healing36). Long-term consumption of glucocorticoids by RA patients can lead to suppression of the hypothalamic-pituitary-adrenal axis, resulting in decreased secretion of corticotropin-releasing hormone and steroidogenic enzymes from the adrenal glands37). This inhibition can lead to reduced secretion of postoperative cortisol and increased potential for development of adrenal insufficiency37). The benefit of administering a physiological dose of glucocorticoids, which is subsequently tapered gradually to preoperative levels, in reducing the risk of these complications has been demonstrated37). Tailoring the dose of glucocorticoids for each patient is critical to obtaining balance between preventing adrenal insufficiency or Addisonian crisis and preventing delay of wound healing and infection37,38). When possible, a patient considered fit to undergo elective THA would be prescribed a daily dose of prednisone or its equivalent that is less than 20 mg39,40).

3. NSAIDs

NSAIDs are commonly used as adjuvants in the treatment of RA and are often used in conjunction with DMARDs41). Aspirin is a commonly used NSAID that primarily targets cyclooxygenase (COX)-1 by irreversibly inhibiting its function. This action plays a role in inhibition of platelet function and thrombosis42,43). Because the action of aspirin is irreversible, the turnover rate of COX rather than the half-life of the drug should be considered in perioperative management44). Platelets have a lifespan of approximately 8 to 10 days, with a turnover rate of 10% per day45). However, hemostasis could occur in normal platelets with 20% of COX-1 activity, achievable within 72 hours46). Therefore, aspirin should be discontinued 72 hours before surgery, and to minimize postoperative risk of bleeding, it can be resumed 8 to 10 days afterward47). Other NSAIDs function as reversible competitive inhibitors to both COX-1 and COX-2, and the dosage and half-life of each medication should be considered when making perioperative drug adjustments44).

Continued use of aspirin without discontinuation is recommended in certain situations48). Recent studies have reported minimal differences in terms of myocardial infarctions or VTE between groups taking aspirin and placebo49). However, maintenance of aspirin therapy without discontinuation is recommended in cases of preexisting cardiovascular disease50).

PREOPERATIVE SURGICAL CONSIDERATIONS

Debate between rheumatologists and orthopedic surgeons regarding the appropriate timing for surgical intervention is ongoing51). Earlier orthopedic surgical intervention is recommended in cases of advanced joint damage due to treatment limitations resulting from significant progression of joint destruction and the acknowledged influence of preoperative joint function on postoperative outcomes52). Conventionally, lower extremities are usually prioritized over upper extremities, with sequential surgery performed on the foot, hip, knee, hindfoot, and ankle38). When arthroplasty is indicated for both knee and hip joints, prioritizing THA prior to total knee arthroplasty can be beneficial38). Prioritizing THA can enable appropriate femoral alignment and length of the lower extremity, as well as achievement of optimal knee flexion due to its capacity to enhance hip joint range of motion53). Cervical spine involvement, which is common in patients with RA, can cause instability, including subaxial instability and basilar invagination54). Hyperextension of the neck is required during intubation under general anesthesia, which can pose a risk in cases of instability. Therefore, assessment of preoperative anteroposterior, lateral cervical plain, flexion and extension radiographs is important41). Regional anesthesia may be necessary in some cases involving instability53). In addition, when general anesthesia is required, fiberoptic intubation may be a suitable anesthetic modality53). Although rare, in severe cases of cervical instability, surgical treatment on the cervical spine may be required before undergoing surgery on the lower extremity to prevent further destruction of the cervical spine or neurological injuries55).

INTRAOPERATIVE SURGICAL CONSIDERATIONS

1. Surgical Approach

While there is no previous research providing clear guidance on the most suitable approach for management of RA patients, the merits of each approach and the surgeon’s preference should be considered when deciding on the surgical approach. The commonly used posterolateral approach enables exceptional visibility of both acetabulum and femur without disrupting the hip abductor muscles by splitting the gluteus maximus muscles to reach the hip joint posteriorly56). By contrast, use of the anterior approach may cause less damage and may be advantageous in management of deformities in hip flexion or external rotation, necessitating removal of the anterior joint capsule57). The findings of a recent retrospective study comparing the correlation between surgical approaches and complications in adults indicated an association of the anterior approach with increased risk of complications including deep infection necessitating surgery, dislocation, and revision arthroplasty compared to the posterior or lateral approaches within one year58). In addition, a trochanteric osteotomy can be initially attempted in cases involving a severe acetabular protrusion deformity that hinders hip dislocation59). In more challenging cases, the Modified Trochanteric Slide Osteotomy technique may be employed to facilitate dislocation with use of the posterolateral or posterior approach60).

Given the rich vascularization of the synovial membrane in RA patients, close attention is required during complete removal of the hypertrophic synovium to minimize excessive bleeding60). Administration of tranexamic acid via intravenous or intra-articular routes is recommended to reduce intraoperative bleeding14).

Characteristics of patients with RA include weakened soft tissues and bone density53). Therefore, soft tissues should be handled with care, and skin damage should be avoided when applying skin retractors. Considering bone density, cortical and cancellous bone can become fragile, potentially leading to bone damage caused by use of traction devices during surgery, perforation of the intramedullary canal, and femoral fractures61). Use of a blunt guide and reaming with an image amplifier is recommended as a preventive measure. Intraoperative femoral fractures usually occur during hip dislocation, thus, when failure of hip dislocation occurs first, neck cutting should be performed prior to dislocation.

2. Implant Selection

Regarding the implants used during surgery, no significant difference associated with use of cement has been reported62). However, recent trends have favored cementless implants62). Arguments in support of using cement typically involve osteoporosis and a wide femoral canal63). A femoral canal can be excessively large, therefore, caution is warranted when using cementless femoral stems64), and in cases of juvenile RA, femoral canals may be too narrow and deformed, potentially necessitating the use of custom-made stems or modular components65).

In THA for patients with RA, hip dislocations are more common in RA patients66). This is often attributed to the use of smaller femoral heads in RA patients, resulting in a short jump distance, loose soft tissues, and poor abductor strength67,68). To minimize dislocations, verifying the anatomical position of the hip center is critical69). Some studies have suggested the use of constrained implants; however, considering the poor bone quality observed in RA patients, use of dual mobility constructs, which have been increasingly used in recent years, may be beneficial70), because similar clinical outcomes can be achieved with use of dual mobility constructs compared to fixed-bearing constructs in performance of THA surgery71).

3. Other Considerations When Planning an Acetabular Procedure

Preparing the acetabulum during performance of THA can be divided into two primary processes: preparation of the acetabular ring and preparation of the acetabular floor. For preparation of the acetabular ring, reamers that are approximately 1-2 sizes smaller than the actual cup size that will be used should be selected. However, for preparation of the acetabular floor, caution is required due to the risk of perforation72). In this case, curettes can be used for selective removal of soft tissues, while perforation of hardened areas can be performed using K-wires to facilitate bleeding.

Protrusio acetabuli, which has been reported in approximately 15%-20% of RA patients, shows slow progression at a rate of 2-3 mm per year73). However, in some cases, rapid progression can lead to rapid worsening of symptoms, requiring specialized attention74). In addition, failure to address protrusio acetabuli, a condition involving contact of the lesser trochanter with the acetabulum, can significantly complicate surgical procedures when performing THA. Bone grafting and use of a standard cup are usually sufficient for milder cases of protrusio acetabuli74). Lee et al.75) also reported that although restoration of the hip center was not achieved in cases with mild protrusio acetabuli, press-fitted cups showed appropriate initial stability and favorable clinical results were obtained. However, in cases with medial wall damage, various plates and rings can be used, and cemented techniques may also be considered74). Although tantalum acetabular cups may be a suitable option, no evidence to support their use in RA patients has been reported74).

4. Others

For RA patients, common complications after hip surgery include infection and wound-related problems76). To avoid such complications, careful hemostasis is required to prevent formation of hematomas. Use of drainage for a specific period after surgery is recommended76). When closing skin, manipulation of soft tissues can be a cause of skin necrosis, blister formation, and secondary infections, which can adversely affect wound healing, and should therefore be minimized, particularly in cases with excessive tension76).

POSTOPERATIVE OUTCOMES AND MANAGEMENT

Close monitoring after surgery is necessary to reduce the risk of complications, particularly for longstanding RA patients77). Patient education is also an important factor in the effort to minimize postoperative complications78). According to a recent systematic review and meta-analysis, the complication rates subsequent to THA for RA patients were higher for hip dislocation, periprosthetic joint infection, wound healing problems, and periprosthetic fracture when compared with osteoarthritis patients66).

Acute flare within six weeks after surgery has been reported in 63% of patients with RA79). However, the reported percentage of patients seeking medical help was 4%, thus education regarding postoperative flare should be provided79). Reassurance is important for these patients as no association with a flare after one year following surgery has been reported80-82).

Concurrent joint pain and deformities should be considered when planning for rehabilitation after surgery. Patients with active RA generally show delayed functional improvement and have longer hospital stays than patients with other conditions83). Therefore, early mobilization and physiotherapy immediately after hip surgery is required for RA patients to prevent immobilization related complications and joint contractures83). In addition, a multi-disciplinary approach should be applied postoperatively, particularly when restarting DMARDs and other RA medications76).

SUMMARY

When performing hip surgery in RA patients, a comprehensive perioperative assessment is essential to achieving favorable outcomes. Medications administered for controlling the activity of RA should be adjusted in cooperation with rheumatologists. In addition, considering the extended duration of RA, preoperative assessment of cardiovascular and pulmonary function, anemia, and the cervical spine is necessary. Considering the unique characteristics of RA patients, factors including soft tissue and bony preparation, as well as implant selection during surgery should be considered. The risk of postoperative complications is higher for RA patients compared to the general population, thus close monitoring is important, and more proactive rehabilitation may be required for recovery.

Funding

No funding to declare.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Table 1 . Recommended Perioperative Modification of RA Medications according to the 2022 ACR/AAHKS Guideline.

MedicationDosing intervalRecommended time for when the surgery is possible since last administration
DMARDs: Not stop through surgery
MTXWeeklyAnytime
SulfasalazineOnce or twice dailyAnytime
HydroxychloroquineOnce or twice dailyAnytime
Leflunomide (Arava®)DailyAnytime
DoxycyclineDailyAnytime
Biologic agents: Stop through surgery (In the absence of systemic infections, surgical site infection or wound healing problem, restart at minimum 14 days after surgery)
Infliximab (Remicade®)Every 4, 6, or 8 weeksWeek 5, 7, or 9
Adalimumab (Humira®)Weekly or every 2 weeksWeek 2 or 3
Etanercept (Enbrel®)Weekly or twice weeklyWeek 2
Golimumab (Simponi®)Every 4 weeks (subcutaneous)
or every 8 weeks (intravenous)		Week 5
Week 9
Abatacept (Orencia®)Monthly (intravenous)
or weekly (subcutaneous)		Week 5
Week 2
Certolizumab (Cimzia®)Every 2 or 4 weeksWeek 3 or 5
Rituximab (Rituxan®)2 doses 2 weeks apart every 4-6 monthsMonth 7
Tocilizumab (Actemra®)Every week (subcutaneous)
or every 4 weeks (intravenous)		Week 2
Week 5
Anakinra (Kineret®)DailyDay 2
IL-17 secukinumab (Cosentyx®)Every 4 weeksWeek 5
Ustekinumab (Stelara®)Every 12 weeksWeek 13
Ixekizumab (Taltz®)Every 4 weeksWeek 5
IL-23 guselkumab (Tremfya®)Every 8 weeksWeek 9
JAK inhibitor: Stop 3 days before surgery
Tofacitinib (Xeljanz®)Daily or twice dailyDay 4
Baricitinib (Olumiant®)DailyDay 4
Upadacitinib (Rinvoq®)DailyDay 4

RA: rheumatoid arthritis, ACR/AAHKS; American College of Rheumatology/American Association of Hip and Knee Surgeons, DMARDs: disease-modifying antirheumatic drugs, MTX: methotrexate, IL: interleukin..

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