Chronic Steroid Use Does Not Increase the Risk of Superficial Surgical Site Infection or Wound Dehiscence Following Total Ankle Arthroplasty

Introduction Total ankle arthroplasty (TAA) is an effective treatment for end-stage ankle arthritis. Recent surgical and technological advances have led to a significant increase in the surgical volume of TAA. While a majority of ankle arthritis is post-traumatic in nature, other causes include autoimmune or inflammatory conditions. Medical management of these conditions frequently requires chronic corticosteroid administration, which is a well-established risk factor for complications following surgery. The purpose of this study was to investigate the association between chronic preoperative steroid use and postoperative complications following TAA. Methods The American College of Surgeons National Surgical Quality Improvement (NSQIP) database was analyzed to identify all patients who underwent TAA between 2015 and 2020. Patient characteristics including demographics, comorbidities, surgical characteristics, and 30-day postoperative complication data were collected. The data was analyzed using bivariate and multivariate logistic regression to identify all postoperative complications associated with chronic preoperative steroid use. Results A total of 1,606 patients were included in this study: 1,533 (95.5%) were included in the non-steroid cohort, and 73 (4.5%) were included in the chronic steroid cohort. Chronic steroid use was significantly associated with female sex (p < 0.001) and American Society of Anesthesiologists (ASA) ≥3 (p < 0.001). Chronic steroid use was not associated with superficial surgical site infection (SSI) (p = 0.634) or wound dehiscence (p = 0.999). The postoperative complication that was significantly associated with chronic steroid use was sepsis (p = 0.031). After adjusting for female sex and the ASA grade, chronic steroid use was found to be independently associated with sepsis (p = 0.013). Conclusion Preoperative chronic steroid use is not associated with superficial SSI or wound dehiscence within 30 days following TAA. As TAA becomes a more attractive alternative to ankle arthrodesis, a better understanding of preoperative risk factors can aid in widening indications and knowing what patients are at risk for complications.


Introduction
Total ankle arthroplasty (TAA) has emerged as an effective alternative to the historical "gold standard" of ankle arthrodesis (AA) for advanced ankle arthritis due to significant improvements in implants [1][2][3].According to a Nationwide Inpatient Sample study, the use of TAA has more than doubled from 390 TAA procedures in 1998 to 844 being performed in 2010 [4].Although TAA has demonstrated the major benefits of better functional recovery and decreased radiographic incidence of adjacent joint degeneration compared to AA, the reoperation rate remains higher than arthrodesis.Therefore, it is important that patients are evaluated on a case-by-case basis to decide between TAA and AA [1,3,[5][6][7].
End-stage ankle arthritis is a major indication for TAA and AA.Unlike hip and knee arthritis, 70% of ankle arthritis is post-traumatic [8].Compared to total hip and total knee arthroplasty, TAA has more frequent complications such as inadequate wound healing and malleolar fractures [9].Other causes of ankle arthritis include mechanical wear and tear or inflammatory or autoimmune conditions [8].Management of inflammatory conditions can include chronic corticosteroid administration, which has been shown to affect long-term survival rates in hip arthroplasty, in addition to being associated with delayed wound healing and increased rates of superficial and deep surgical site infections (SSIs) after surgery [10][11][12][13][14][15].Although chronic steroid use may be less frequent in TAA patients due to the more traumatic nature of ankle arthritis, the inherent postoperative risk factors associated with TAA make it important to investigate whether chronic steroid use increases the risk of postoperative complications.
Previous studies have investigated the association of chronic steroid use and postoperative complications in lumbar fusion, knee, hip, and shoulder arthroplasty [10,12,[16][17][18].Chronic steroid use was found to be an independent risk factor for SSIs, pneumonia, urinary tract infections, and readmission for all of these procedures.However, there have been no investigations into the association between preoperative chronic steroid use and postoperative complications following TAA.As TAA has previously demonstrated a higher rate of reoperation than AA due to deep infection, this investigation can aid in the decision-making process of proceeding with TAA versus AA [19].
The purpose of this study was to investigate preoperative chronic steroid use and its association with postoperative complications following TAA to improve perioperative planning and risk stratification.We hypothesized that chronic steroid use would be associated with increased rates of postoperative infections following TAA.Patients were divided into chronic steroid and non-steroid groups.The chronic steroid cohort consisted of patients who required regular administration of parenteral or oral corticosteroid medication and received such medication within the 30-day preoperative period.Non-steroid users included patients who received short-term steroids over 10 days or less during the 30-day preoperative period and who received corticosteroids dermally, rectally, or via inhalation.

Materials And Methods
A total of 1,825 patients underwent primary TAA in NSQIP from 2015 to 2020.Cases were excluded as follows: eight for missing height/weight, 23 for missing functional health status, one for missing discharge destination, and 187 for revision procedure.Of the 1,606 patients remaining after exclusion criteria, 1,533 (95.5%) patients were included in the non-steroid cohort, and 73 (4.5%) patients were included in the chronic steroid cohort.This is outlined in Figure 1.

FIGURE 1: Strengthening the reporting of observational studies in epidemiology (STROBE) diagram with inclusion and exclusion criteria
TAA: Total ankle arthroplasty; NSQIP: National Surgical Quality Improvement Program.
All statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS) software, version 26.0 (IBM Corp., Armonk, NY).Patient demographics and comorbidities were compared between cohorts using bivariate analysis.Multivariate logistic regression, adjusted for all significantly associated patient demographics and comorbidities, was used to identify associations between preoperative chronic steroid use and postoperative complications.Odds ratios (OR) were reported with 95% confidence intervals (CI).The level of statistical significance was set at p < 0.05 [18].

Results
Bivariate analysis was used to determine patient demographics and comorbidities which were significantly associated with preoperative chronic steroid use (Table 1).The only patient demographics that were significantly associated with preoperative chronic steroid use were female gender (p < 0.001) and ASA ≥ 3 (p < 0.001).The chronic steroid cohort had 67.1% females, compared to 44.0% in the non-steroid cohort group.The chronic steroid cohort also had 63.0% with an ASA classification ≥ 3, compared to 39.6% in the nonsteroid cohort group.Bivariate analysis was used to determine postoperative complications associated with preoperative chronic steroid use versus non-steroid use (Table 2).Chronic steroid use was not associated with superficial SSI (p = 0.634) or wound dehiscence (p = 0.999).The only postoperative complication that was significantly associated with preoperative chronic steroid use was sepsis (p = 0.031).Multivariate logistic regression analysis was used to adjust the patient variables that were significantly associated with chronic steroid use (female gender and ASA ≥ 3).Multivariate logistic regression identified sepsis (OR: 38.46; 95% CI: 2.14-690.20;p = 0.013) to be independently associated with preoperative chronic steroid use (Table 2).

Discussion
The most important finding of this study was the lack of association between chronic steroid use and wound dehiscence or superficial SSI.Thirty-day postoperative complications and their association with chronic steroid use in patients who underwent TAA from 2015 to 2020 using a large national database were reported.Our analysis included 1,606 patients, and 73 (4.5%) patients in this group were prescribed steroids for a chronic condition.Through bivariate analysis, we identified chronic steroid use as a possible risk factor for sepsis and found no association between chronic corticosteroid use and superficial SSI or wound dehiscence.
After controlling for significantly associated patient demographics and comorbidities, we identified that chronic steroid use does place patients at increased risk of sepsis following TAA.
Due to recent technological advances, there has been a notable resurgence in the use of TAA for the management of end-stage ankle arthritis.Due to a steady increase in the surgical volume of TAA, there is a growing importance of understanding patient risk factors and their effects on patient outcomes.One wellrecognized surgical risk factor is chronic corticosteroid use [11,14].Corticosteroids are potent immunomodulators that exert anti-inflammatory effects through inhibition of key inflammatory pathways (e.g., cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor alpha, and pro-inflammatory cytokines) via direct effects on gene regulation [11,20].In the setting of autoimmune or inflammatory disease states, these effects prevent inadvertent damage to surrounding structures through a hyper-reactive immune response.However, the effects of corticosteroids also interfere with a wide range of normal metabolic processes, leading to a multitude of common side effects and complications from long-term steroid use [11,20].
Established side effects of chronic steroid use include impaired wound healing, increased susceptibility to infection, osteopenia/osteoporosis, impaired glycemic control, avascular necrosis, and muscle atrophy [11,14,20].These side effects may significantly impact postoperative outcomes.Thus, patients with chronic autoimmune or inflammatory diseases that require chronic corticosteroid use need close monitoring and careful evaluation before surgery [11].Within the orthopedic community, current literature has established associations between chronic steroid use and adverse outcomes following total hip, knee, and shoulder arthroplasties [12,18].However, there is a paucity of literature surrounding chronic steroid use and TAA.Our study addresses this gap in the literature through the use of a large national database.
Our study found that chronic steroid use in patients who underwent TAA was associated with female gender and an ASA classification ≥ 3.These discrepancies in patient gender and ASA classification are not particularly surprising.First, steroid use is a cornerstone in the management of autoimmune diseases, which has a higher prevalence in females compared to males [21].Second, chronic steroid use is typically reserved for patients with severe inflammatory disease that is refractory to other therapeutic modalities [20].This level of disease severity would meet the criteria for ASA classification ≥ 3, which is described as a "patient with severe systemic disease" [22].Interestingly, after controlling these factors and based on the available data, chronic steroid use was not identified as an independent risk factor for postoperative superficial SSI or wound dehiscence after TAA.
Our finding that preoperative chronic steroid use does not increase the risk of superficial SSI or wound dehiscence following TAA is not completely consistent with previous studies in total joint arthroplasty.This is possibly due to the differing causes for end-stage ankle arthritis compared to other joints treated with arthroplasty.A study by Poss et al. reported that patients with rheumatoid arthritis treated with chronic steroids who underwent total joint arthroplasty had an increased risk of postoperative infection and sepsis that extended years after their procedure [23].Another study on total hip arthroplasty by Boddapati et al. demonstrated that patients with chronic steroid use had roughly twice the 30-day readmission rate compared to patients without chronic steroid use.Importantly, infections accounted for approximately onethird of these readmissions [10].A major cause for our findings may be a cause for end-stage ankle arthritis being largely caused by previous trauma.Notably, there was a relatively small proportion of patients using steroids chronically, which may reflect an overall healthier cohort.
In a similar study looking at chronic steroid use in total shoulder arthroplasty, Ling et al. reported chronic steroid use as a significant risk factor for septic shock within 30 days postoperatively [18].This finding is consistent with one of our findings that chronic steroids may lead to an increased risk of sepsis.However, with only one case of sepsis seen in the chronic steroid cohort, this correlation may need further investigation.Notably, Ling et al. also did not find a significant correlation between chronic steroid use and superficial SSI or wound dehiscence [18].Additionally, our findings are consistent with a recent metaanalysis and systematic review conducted by Mousavian et al., which demonstrated comparable complication rates between inflammatory and noninflammatory arthritis patients undergoing TAA [24].This meta-analysis supports our conclusion that TAA is a safe and effective procedure in patients who may be taking chronic steroids for inflammatory arthritis.
This study was constrained by some inherent limitations of using the NSQIP database.One major limitation of the study is the limited number of cases involving patients with chronic steroid use.Further investigation is needed to determine if sepsis is associated with chronic steroid use over a larger population of users.In addition, although the use of TAA has been increasing, it is still relatively uncommon with respect to other joint arthroplasties, resulting in a relatively smaller sample size.Additionally, the NSQIP database does not provide information on the indication for chronic steroid use.Therefore, we were unable to account for the disease for which chronic steroids were prescribed.Furthermore, the postoperative complications recorded in NSQIP are only limited to the 30-day postoperative period.As indicated in the study by Poss et al., infectious complications following TAA may extend to years beyond the procedure, so a 30-day postoperative window may not be representative of the adverse effects of chronic steroid use [23].
Additionally, the study is limited by a possibly different presentation of SSI due to chronic steroid use.Due to the suppression of their immune system in combination with the 30-day window, SSI may be missed in some of these patients.This may also result in an increased risk of sepsis that is not observed.
Although this study is not without limitations, a large national database was utilized to identify patients undergoing TAA and analyze postoperative complications associated with preoperative chronic steroid use.While patients may need further investigation for risk of sepsis, chronic steroid use should not be seen as a contraindication for the procedure.As the surgical volume for TAA continues to grow, further studies are needed to better assess both sepsis risk with a larger cohort and long-term postoperative complications associated with chronic steroid use.

Conclusions
Preoperative chronic steroid use is not a risk factor for superficial SSI or wound dehiscence within 30 days following TAA.Chronic steroid users who underwent TAA were more likely to be female with an ASA ≥ 3.As TAA continues to become a more attractive alternative to AA, a better understanding of preoperative risk factors can aid in widening indications and knowing who are truly at risk for complications.

2024
Garcia et al.Cureus 16(1): e52569.DOI 10.7759/cureus.52569 This study identified patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database who underwent TAA from 2015 to 2020.This study was exempt from approval by our university's Institutional Review Board as it only utilized fully deidentified info from the NSQIP database.Over 600 hospitals in the United States contribute to the NSQIP database, and data was obtained by trained surgical clinical reviewers.

TABLE 2 : Bivariate and multivariate analysis of 30-day postoperative complications in patients with and without chronic steroid use
SSI: Surgical site infection; CI: Confidence interval.