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Chronic preoperative corticosteroid use is not associated with surgical site infection following revision total knee arthroplasty
Journal of Orthopaedics 20 (2020) 173–176
Contents lists available at ScienceDirect
Journal of Orthopaedics journal homepage: www.elsevier.com/locate/jor
Original Article
Chronic preoperative corticosteroid use is not associated with surgical site infection following revision total knee arthroplasty☆
T
Safa C. Fassihi (MD)a,∗, Alex Gu (BS)a,b, Dana A. Perim (BS)a, Chapman Wei (BS)a, Seth Stake (MD)a, Savyasachi Thakkar (MD)c, Anthony S. Unger (MD)d, Michael P. Ast (MD)e, Peter K. Sculco (MD)b a
Department of Orthopedic Surgery, George Washington School of Medicine and Health Sciences, 2300 Eye St NW, Washington DC, 20037, USA Complex Joint Reconstruction Center, Hospital for Special Surgery, 535 E 70th St, New York City, NY, 10021, USA c Department of Orthopaedic Surgery, MedStar Georgetown Orthopaedic Institute at Washington Hospital Center, 110 Irving St NW, Washington DC, 20010, USA d Gildenhorn Institute of Bone and Joint Health, Sibley Memorial Hospital, 5255 Loughboro Road NW, Washington, DC, 20016, USA e Adult Reconstruction and Joint Replacement, Hospital for Special Surgery, 535 E 70th St, New York City, NY, 10021, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Corticosteroid Steroid Total knee arthroplasty Complication Revision
Introduction: The objective of this study was to determine whether chronic preoperative corticosteroid use is associated with increased infectious complications following revision total knee arthroplasty (rTKA). Methods: A retrospective cohort analysis was conducted using patients from a large national database. Patients were divided into two cohorts based upon chronic steroid usage preoperatively. Infectious complications in the 30-day postoperative period were recorded, and univariate and multivariate analyses were performed. Results: A total of 10,973 patients were included in this study. No significant difference was observed in surgical site infection rates between patients with and without preoperative steroid use. In multivariate analysis, preoperative steroid use was independently associated with an increased likelihood of septic shock (OR 6.17; p = 0.015) and prolonged length-of-stay (OR 1.57; p = 0.038). Conclusion: Chronic preoperative steroid is not a significant risk factor for surgical site infection following rTKA, but it is independently associated with increased risk of septic shock and prolonged hospital length of stay.
1. Introduction Total knee arthroplasty (TKA) is presently one of the most commonly performed orthopaedic procedures.1 The total number of primary TKAs performed annually is projected to increase to 3.48 million by 2030.2 With a 10-year revision rate of 5%, the burden of revision surgery is significant and will continue to grow.2,3 Compared to primary TKA, revision TKA (rTKA) is associated with increased incidence of postoperative infection. While the rate of surgical site infections for primary TKA has been estimated to range from 0.2% to 2%,4 the incidence of infection after revision TKA for aseptic indications has been reported to be as high as 5%.5,6 Thus, this group of patients deserves critical attention. Corticosteroid use is one potential risk factor for postoperative complications. Used for the treatment of a wide variety of diseases, corticosteroids are one of the most commonly prescribed classes of drugs in the United States.7 The effect of corticosteroids on
postoperative complications is a topic of concern across surgical subspecialties.8–11 Preoperative steroid use has been associated with an increased risk of wound complications, postoperative infections, and respiratory, renal, and cardiac events.8,12 Furthermore, it has been associated with increased overall morbidity and mortality.12 For many patients, discontinuation of steroids preoperatively is not possible, adding an unmodifiable risk factor for patients who often already have other comorbidities.9,10 While previous work has found that 3% of the population undergoing primary TKA procedures were on chronic steroids preoperatively,10 there is limited data on rates of steroid use or associated complications in patients undergoing rTKA. The purpose of this study was to determine: 1) Are patients on chronic preoperative corticosteroids at increased risk for early (≤30 days) postoperative infectious complications? 2) Does chronic steroid use increase the risk of extended hospital stay, unplanned return to the operating room, or patient mortality?
☆ ∗
No benefits in any form have been received or will be received from a commercial entity related directly or indirectly to the subject of this article. Corresponding author. E-mail address: [email protected] (S.C. Fassihi).
https://doi.org/10.1016/j.jor.2020.01.044 Received 20 January 2020; Accepted 25 January 2020 Available online 28 January 2020 0972-978X/ © 2020 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.
Journal of Orthopaedics 20 (2020) 173–176
S.C. Fassihi, et al.
2. Methods
Table 1 Demographic features and clinical characteristics of patients undergoing revision total knee arthroplasty.
The American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) database was queried retrospectively for patients who underwent revision total knee arthroplasties from the years 2007–2016. ACS-NSQIP is a large multicenter registry which collects data on 135 variables including preoperative demographic information and risk factors, perioperative events, and postoperative complications occurring within 30 days, for patients undergoing a wide variety of both orthopaedic and non-orthopaedic surgical procedures. Registry data is prospectively collected on a continuous basis by trained reviewers. The data is routinely audited and has been demonstrated to have high inter-observer reliability.13 Patients undergoing revision total knee arthroplasty were identified using Current Procedural Terminology (CPT) codes 27486, 27487 and 27488. Patients who had an infectious etiology for revision TKA were excluded from this study. Infectious etiology was determined by ICD-9 and ICD-10 codes. Two patient cohorts were defined in this study: (1) patients with chronic preoperative steroid usage and (2) patients without chronic preoperative steroid usage. ACS-NSQIP defines chronic preoperative corticosteroid use as “patients who required regular administration of oral or parenteral corticosteroid medications in the 30 days before surgery for a chronic medical condition.”14 Patient demographics of interest and clinical characteristics collected included patient age, sex, race, and Body Mass Index (BMI), which was stratified according to the World Health Organization classification. Total length of stay (LOS), absence or severity of dyspnea, smoking history, preoperative functional status, type of anesthesia, and American Society of Anesthesiologists (ASA) class were also collected. Patient comorbidities and operative features collected included transfusion requirements, pulmonary comorbidities, cardiac comorbidities, renal failure, dialysis requirement, history of recent weight loss, bleeding disorder, ascites, and diabetes mellitus status. Recorded 30-day postoperative complications included superficial and deep surgical site infections (SSI), organ space infection, wound dehiscence, urinary tract infection, sepsis, septic shock, death, return to operating room, and extended hospital LOS. Extended hospital LOS was defined as > 7 days in the hospital postoperatively. In order to determine their association with chronic preoperative steroid use, data on patient demographics, comorbidities, and postoperative infectious complications were analyzed with univariate analysis using Pearson's Chi-squared test. Variables with p < 0.05 were selected for multivariate analysis. For multivariate analysis, binary logistic linear regression analysis was performed to determine whether chronic steroid was an independent risk factor for infectious complications, extended LOS, return to the operating room, and patient mortality. Multivariate analysis results were reported as odds ratios with 95% confidence intervals. A p-value of < 0.05 was used as the cutoff for significance.
Demographics
Steroid
No Steroid
474
10499
N
%
Sex Male 137 28.9% Female 337 71.1% Race White 351 74.1% Black or African American 78 16.5% Hispanic 24 5.1% American Indian or Alaska Native 11 2.3% Asian 8 1.7% Native Hawaiian or Pacific Islander 2 0.4% Anesthesia Type General 289 61.0% Regional 151 31.9% Monitored Anesthesia Care/ 34 7.2% Intravenous Sedation Diabetes Mellitus Status No Diabetes Mellitus 397 83.8% Non-Insulin-Dependent Diabetes 49 10.3% Mellitus Insulin-Dependent Diabetes 31 6.5% Mellitus American Association of Anesthesiologists Score 1 or 2 105 22.2% 3 or 4 369 77.8% Dyspnea Status No dyspnea 414 87.3% Moderate exertion 57 12.0% At rest 3 0.6% Functional Status Independent 440 92.8% Partially Dependent 33 7.0% Totally Dependent 1 0.2% History of Smoking 49 10.34% BMI 18.5–30 201 42.4% 30–34.9 104 21.9% 35–39.9 88 18.6% > 40 81 17.1% Age < 50 41 8.6% 51–60 107 22.6% 61–70 182 38.4% 71–80 108 22.8% 80+ 36 7.6%
N
%
4102 6397
39.1% 60.9%
8447 1401 463 52 97 39
80.5% 13.3% 4.4% 0.5% 0.9% 0.4%
6436 3293 770
61.3% 31.4% 7.3%
8301 1508
79.1% 14.4%
690
6.6%
4517 5982
43.0% 57.0%
9773 705 21
93.1% 6.7% 0.2%
10162 325 12 1240
96.8% 3.1% 0.1% 11.81%
3697 2957 2037 1808
35.2% 28.2% 19.4% 17.2%
845 2697 3702 2474 781
8.0% 25.7% 35.3% 23.6% 7.4%
p-value
< 0.001
< 0.001
0.971
0.016
< 0.001
< 0.001
< 0.001
0.33 0.004
0.506
Table 2 Comorbidities of patients undergoing revision total knee arthroplasty. Comorbidities
Steroid Use
No Steroid Use
3. Results
474
10499
3.1. Demographics
N
%
N
%
42 327 1 2 3 25 0 5
8.9% 69.0% 0.2% 0.4% 0.6% 5.3% 0.00% 1.1%
507 7025 4 32 25 355 2 38
4.8% 66.9% 0.0% 0.3% 0.2% 3.4% 0.02% 0.4%
Pulmonary Comorbidities Cardiac comorbidities Renal Failure Dialysis Weight loss Bleeding disorder Ascites Preoperative Transfusion
A total of 10,973 patients underwent rTKA and met inclusion criteria for the study. In total, 474 of the included patients were on preoperative steroid therapy (4.3%) and 10,499 patients (95.7%) were not. Patients on preoperative steroids were more likely to be female (p < 0.001), identify as non-white (p < 0.001), have a higher ASA class (p < 0.001), have dyspnea (p < 0.001), be less functionally independent (p < 0.001), and have a lower BMI (p = 0.004; Table 1).
p-value
< 0.001 0.347 0.085 0.654 0.096 0.027 0.764 0.018
bleeding disorder (p = 0.027), and require preoperative transfusion (p = 0.018) when compared to patients not on preoperative corticosteroid treatment (Table 2).
3.2. Comorbidities Patients on corticosteroid therapy were more likely to have a history of pulmonary disease (p < 0.001), be non-diabetic (p = 0.016), have a 174
Journal of Orthopaedics 20 (2020) 173–176
S.C. Fassihi, et al.
postoperative infectious complications following revision TKA. In our analysis, chronic corticosteroid use was not associated with an increased risk of surgical site infection after revision rTKA. This is consistent with previous work by Luessenhop et al., who retrospectively assessed various risk factors for periprosthetic joint infection (PJI) in patients undergoing primary total joint arthroplasty. They found that while corticosteroid use was a significant risk factor for PJI, it was not a significant risk factor when controlling for patients with rheumatoid arthritis on multiple regression analysis. This suggests that the condition for which the corticosteroids are being used, not the medication itself, may be responsible for any increases in infection risk seen in this patient population.23 In contrast to these findings, Salt et al. performed a retrospective, case-control analysis on 2212 patients undergoing primary total joint arthroplasty and found that prednisone was an independent risk factor for postoperative infection.24 Additionally, Somayaji et al. found that there is a dose-dependent effect of corticosteroids on infection risk, as only prednisone doses exceeding 15 mg/day were associated with increased risk of postoperative infection in patients with rheumatoid arthritis undergoing total joint arthroplasty.25 Lastly, in an ACS-NSQIP analysis of patients undergoing all-cause surgery from 2005 to 2008, Ismael et al. found that preoperative corticosteroid use was associated with increased risk of superficial SSI, deep SSI, organ/space SSI, wound dehiscence, and mortality.8 While the exact association between chronic preoperative steroid use and postoperative infection following total joint arthroplasty remains to be clearly elucidated, the present study adds to the growing body of evidence and is the first of its kind to focus on revision TKA. Our analysis found that chronic corticosteroid use was independently associated with increased rates of septic shock and extended hospital length of stay following rTKA. To the authors’ knowledge, these specific findings that have not been previously associated with chronic preoperative steroid use, even for other types of surgery. Increased rates of septic shock and extended LOS may be an indication that chronic steroid use reflects poorer underlying health, as these patients may be physiologically frailer and take longer to recover from surgery. This notion is corroborated by our findings that patients on preoperative steroids were more likely to have dyspnea, have a higher ASA status, and be less functionally independent. Given the extended LOS seen in these patients, clinicians should counsel these patients preoperatively on their risk of prolonged hospitalization following rTKA in order to appropriately set expectations. Additionally, postoperative infections should be managed in a more aggressive fashion to prevent progression to septic shock, as these patients are at an increased risk of this complication by virtue of their corticosteroid use. There were several limitations to this study. First, there are inherent limitations to the use of the ACS-NSQIP database. Dose, duration, and indications for chronic steroid therapy are not reported in this database, introducing the possibility that numerous variables may be confounding the findings. Additionally, only short-term complication rates can be analyzed, as the ACS-NSQIP database only tracks patients for the first 30 days postoperatively. It is plausible that continued corticosteroid use places the patients at greater risk of PJI beyond the immediate perioperative period, but this cannot be accounted for with the present data. Another limitation of all database studies is the use of CPT codes for research purposes. As CPT codes were initially developed for billing purposes, the utilization of these codes represents a potential confounding variable that cannot be accounted for. Reporting based on financial incentive can introduce coding bias that could theoretically include more minor procedures that are not truly rTKA. Furthermore, the possibility of human error in reporting of data is a limitation that pervades all database analyses. Lastly, a major limitation of retrospective research is the inability to show causality, as our study shows an association between chronic corticosteroid use and both septic shock and extended hospital LOS, but it cannot demonstrate a cause-and-effect relationship.
Table 3 Univariate analysis of association between chronic steroid use and postoperative complications in patients undergoing revision total knee arthroplasty. Complications
Superficial surgical site infection Deep Wound Infection Organ/Space Infection Wound Dehiscence Pneumonia Urinary tract Infection Sepsis Septic Shock Death Other Outcomes Extended Length of Stay (> 7 days) Return to Operating Room
Steroid
No Steroid
474
10499
p-value
N
%
N
%
1 4 4 2 3 6 4 3 3
0.2% 0.8% 0.8% 0.4% 0.6% 1.3% 0.8% 0.6% 0.6%
71 53 74 42 41 77 39 8 20
0.7% 0.5% 0.7% 0.4% 0.4% 0.7% 0.4% 0.1% 0.2%
0.220 0.315 0.724 0.941 0.414 0.191 0.107 < 0.001 0.039
26 14
5.5% 2.95%
275 332
2.6% 3.16%
< 0.001 0.799
3.3. Postoperative complications On univariate analysis, patients on preoperative steroids were significantly more likely to experience septic shock (0.6% vs 0.1%; p < 0.001), death (0.6% vs 0.2%; p = 0.039), and extended hospital LOS (5.5% vs 2.6%; p < 0.001; Table 3). Preoperative corticosteroid use was not associated with an increased risk of surgical site infections. On multivariate analysis, chronic corticosteroid use was an independent risk factor for septic shock (OR 6.174, 95% CI 1.422–26.812; p = 0.015) and extended hospital LOS (OR 1.572, 95% CI 1.025–2.415; p < 0.038; Table 4). 4. Discussion While the overall rate of revision after primary TKA remains low, the projected increase in demand for rTKA represents a potential healthcare burden. Furthermore, the mean total cost of an rTKA procedure has been increasing with time.15,16 Ong et al. found that patients undergoing rTKA were placed at a 5–6 times higher risk of needing a subsequent revision surgery relative to those undergoing primary TKA.17 Re-revisions present a major challenge both medically and financially. The potentially catastrophic impact on patients and significant resource burden on the healthcare system emphasizes the need to identify potential complications of rTKA and risk factors for them. Chronic corticosteroid use is a risk factor for poor wound healing and negative surgical outcomes,8,11,18,19 as chronic steroid use impairs vascular permeability, chemotaxis, leukocyte adhesion and phagocytosis, all of which are critical for tissue repair and defense against infection.11,20–22 Despite these known physiologic effects, there is a paucity of data on the effects of chronic corticosteroid use on infection rates following total joint arthroplasty. Previous studies of steroid use in the setting of arthroplasty have yielded mixed results and are confounded by the presence of inflammatory arthropathy in this subset of patients.23–25 To our knowledge, this is the first study to directly examine the relationship between chronic glucocorticoid use and Table 4 Multivariate analysis of postoperative complications associated with chronic steroid use on univariate analysis. Postoperative complication
Septic Shock Death Extended Length of Stay (> 7 days)
p-value
0.015 0.308 0.038
Odds Ratios
6.174 1.916 1.572
95% CI lower
higher
1.422 0.509 1.025
26.812 3.043 2.415
175
Journal of Orthopaedics 20 (2020) 173–176
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5. Conclusion
2010;468. https://doi.org/10.1007/s11999-010-1308-6 2052–9. 6. Joint A, Registry R, Report A. American Joint Replacement Registry 2017 Annual Report Fourth AJRR Annual Report on Hip and Knee Arthroplasty Data. 2017; 2017. 7. Fuentes A, Pineda M, Venkata K. Comprehension of top 200 prescribed drugs in the US as a resource for pharmacy teaching, training and practice. Pharmacy. 2018;6:43. https://doi.org/10.3390/pharmacy6020043. 8. Ismael H, Horst M, Farooq M, Jordon J, Patton JH, Rubinfeld IS. Adverse effects of preoperative steroid use on surgical outcomes. Am J Surg. 2011;201:305–309. https://doi.org/10.1016/j.amjsurg.2010.09.018. 9. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids:A systematic review of the literature. Arch Surg. 2008;143:1222–1226. 10. Zarling BJ, Sikora-Klak J, Bergum C, Markel DC. How do preoperative medications influence outcomes after total joint arthroplasty? J Arthroplasty. 2017;32:S259–S262. https://doi.org/10.1016/j.arth.2017.04.031. 11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11:954–963. 12. van Zaane B, Nur E, Squizzato A, et al. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemostasis. 2010;8:2483–2493. https://doi.org/10.1111/j.1538-7836.2010. 04034.x. 13. Surgeons Ac of American College of Surgeons National Surgical Quality Improvement Program 2015:1–41. 14. National Surgical Quality Improvement Program. User Guide for 2012 ACS NSQIP Participant Use Data File. Chicago, IL: American College of Surgeons; 2013 Available at: https://www.facs.org/~/media/files/quality%20programs/nsqip/ug12.ashx. 15. Oduwole KO, Molony DC, Walls RJ, Bashir SP, Mulhall KJ. Increasing financial burden of revision total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2010;18:945–948. https://doi.org/10.1007/s00167-010-1074-8. 16. Kallala RF, Vanhegan IS, Ibrahim MS, Sarmah S, Haddad FS. Financial analysis of revision knee surgery based on NHS tariffs and hospital costs: does it pay to provide a revision service? Bone Joint Lett J. 2015;97–B:197–201. https://doi.org/10.1302/ 0301-620X.97B2.33707. 17. Ong KL, Lau E, Suggs J, Kurtz SM, Manley MT. Risk of subsequent revision after primary and revision total joint arthroplasty. Clin Orthop Relat Res. 2010;468:3070–3076. https://doi.org/10.1007/s11999-010-1399-0. 18. Ginzler E, Diamond H, Kaplan D, Weiner M, Schlesinger M, Seleznick M. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum. 1978;21:37–44. 19. Everhart JS, Andridge RR, Scharschmidt TJ, Mayerson JL, Glassman AH, Lemeshow S. Development and validation of a preoperative surgical site infection risk score for primary or revision knee and hip arthroplasty. J Bone Joint Surg Am. 2016;98:1522–1532. https://doi.org/10.2106/JBJS.15.00988. 20. Greaves MW. Anti-inflammatory action of corticosteroids. Postgrad Med. 1976;52:631–633. 21. Jamal A, Homa DM, O'Connor E, et al. Current cigarette smoking among adults — United States, 2005–2014. MMWR Morb Mortal Wkly Rep. 2015;64:1233–1240. https://doi.org/10.15585/mmwr.mm6444a2. 22. Anstead GM. Steroids, retinoids, and wound healing. Adv Wound Care. 1998;11:277–285. 23. Luessenhop C, Higgins L, Brause B, Ranawat C. Multiple prosthetic infections after total joint arthroplasty. J Arthroplasty. 1996;11(7):862–868. https://doi.org/10. 1016/S0883-5403(96)80189-6. 24. Salt E, Wiggins AT, Rayens MK, et al. Moderating effects of immunosuppressive medications and risk factors for post-operative joint infection following total joint arthroplasty in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 2017;46(4):423–429. https://doi.org/10.1016/j.semarthrit.2016.08.011. 25. Somayaji R, Barnabe C, Martin L. Risk factors for infection following total joint arthroplasty in rheumatoid arthritis. Open Rheumatol J. 2013;7:119–124. https://doi. org/10.2174/1874312920131210005 Published 2013 Nov 29.
In this large national database analysis, chronic corticosteroid use was found to be independently associated with septic shock and extended hospital LOS following revision TKA. Notably, there was no increase in surgical site infections with chronic preoperative steroid use. Surgeons should counsel these patients on their increased risk of requiring an extended hospitalization following rTKA in order to appropriately set expectations. Furthermore, if these patients develop signs or symptoms of infection, clinicians should have a low threshold for aggressive treatment in order to prevent progression to septic shock. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of competing interest The authors of this manuscript certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patentlicensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) directly related to the subject matter or materials discussed in this manuscript. Acknowledgements None. References 1. Mistry JB, Elmallah RK, Chughtai M, Oktem M, Harwin SF, Mont MA. Long-term survivorship and clinical outcomes of a single radius total knee arthroplasty. Surg Technol Int. 2016;28:247–251. 2. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Jt Surg - Ser A. 2007;89:780–785. https://doi.org/10.2106/JBJS.F.00222. 3. Khan M, Osman K, Green G, Haddad FS. The epidemiology of failure in total knee arthroplasty. Bone Joint Lett J. 2016;98–B:105–112. https://doi.org/10.1302/0301620X.98B1.36293. 4. Pugely AJ, Martin CT, Gao Y, Schweizer ML, Callaghan JJ. The incidence of and risk factors for 30-day surgical site infections following primary and revision total joint arthroplasty. J Arthroplasty. 2015;30:47–50. https://doi.org/10.1016/j.arth.2015.01. 063. 5. Mortazavi SMJ, Schwartzenberger J, Austin MS, Purtill JJ, Parvizi J. Revision total knee arthroplasty infection: incidence and predictors. Clin Orthop Relat Res.
176
Contents lists available at ScienceDirect
Journal of Orthopaedics journal homepage: www.elsevier.com/locate/jor
Original Article
Chronic preoperative corticosteroid use is not associated with surgical site infection following revision total knee arthroplasty☆
T
Safa C. Fassihi (MD)a,∗, Alex Gu (BS)a,b, Dana A. Perim (BS)a, Chapman Wei (BS)a, Seth Stake (MD)a, Savyasachi Thakkar (MD)c, Anthony S. Unger (MD)d, Michael P. Ast (MD)e, Peter K. Sculco (MD)b a
Department of Orthopedic Surgery, George Washington School of Medicine and Health Sciences, 2300 Eye St NW, Washington DC, 20037, USA Complex Joint Reconstruction Center, Hospital for Special Surgery, 535 E 70th St, New York City, NY, 10021, USA c Department of Orthopaedic Surgery, MedStar Georgetown Orthopaedic Institute at Washington Hospital Center, 110 Irving St NW, Washington DC, 20010, USA d Gildenhorn Institute of Bone and Joint Health, Sibley Memorial Hospital, 5255 Loughboro Road NW, Washington, DC, 20016, USA e Adult Reconstruction and Joint Replacement, Hospital for Special Surgery, 535 E 70th St, New York City, NY, 10021, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Corticosteroid Steroid Total knee arthroplasty Complication Revision
Introduction: The objective of this study was to determine whether chronic preoperative corticosteroid use is associated with increased infectious complications following revision total knee arthroplasty (rTKA). Methods: A retrospective cohort analysis was conducted using patients from a large national database. Patients were divided into two cohorts based upon chronic steroid usage preoperatively. Infectious complications in the 30-day postoperative period were recorded, and univariate and multivariate analyses were performed. Results: A total of 10,973 patients were included in this study. No significant difference was observed in surgical site infection rates between patients with and without preoperative steroid use. In multivariate analysis, preoperative steroid use was independently associated with an increased likelihood of septic shock (OR 6.17; p = 0.015) and prolonged length-of-stay (OR 1.57; p = 0.038). Conclusion: Chronic preoperative steroid is not a significant risk factor for surgical site infection following rTKA, but it is independently associated with increased risk of septic shock and prolonged hospital length of stay.
1. Introduction Total knee arthroplasty (TKA) is presently one of the most commonly performed orthopaedic procedures.1 The total number of primary TKAs performed annually is projected to increase to 3.48 million by 2030.2 With a 10-year revision rate of 5%, the burden of revision surgery is significant and will continue to grow.2,3 Compared to primary TKA, revision TKA (rTKA) is associated with increased incidence of postoperative infection. While the rate of surgical site infections for primary TKA has been estimated to range from 0.2% to 2%,4 the incidence of infection after revision TKA for aseptic indications has been reported to be as high as 5%.5,6 Thus, this group of patients deserves critical attention. Corticosteroid use is one potential risk factor for postoperative complications. Used for the treatment of a wide variety of diseases, corticosteroids are one of the most commonly prescribed classes of drugs in the United States.7 The effect of corticosteroids on
postoperative complications is a topic of concern across surgical subspecialties.8–11 Preoperative steroid use has been associated with an increased risk of wound complications, postoperative infections, and respiratory, renal, and cardiac events.8,12 Furthermore, it has been associated with increased overall morbidity and mortality.12 For many patients, discontinuation of steroids preoperatively is not possible, adding an unmodifiable risk factor for patients who often already have other comorbidities.9,10 While previous work has found that 3% of the population undergoing primary TKA procedures were on chronic steroids preoperatively,10 there is limited data on rates of steroid use or associated complications in patients undergoing rTKA. The purpose of this study was to determine: 1) Are patients on chronic preoperative corticosteroids at increased risk for early (≤30 days) postoperative infectious complications? 2) Does chronic steroid use increase the risk of extended hospital stay, unplanned return to the operating room, or patient mortality?
☆ ∗
No benefits in any form have been received or will be received from a commercial entity related directly or indirectly to the subject of this article. Corresponding author. E-mail address: [email protected] (S.C. Fassihi).
https://doi.org/10.1016/j.jor.2020.01.044 Received 20 January 2020; Accepted 25 January 2020 Available online 28 January 2020 0972-978X/ © 2020 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.
Journal of Orthopaedics 20 (2020) 173–176
S.C. Fassihi, et al.
2. Methods
Table 1 Demographic features and clinical characteristics of patients undergoing revision total knee arthroplasty.
The American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) database was queried retrospectively for patients who underwent revision total knee arthroplasties from the years 2007–2016. ACS-NSQIP is a large multicenter registry which collects data on 135 variables including preoperative demographic information and risk factors, perioperative events, and postoperative complications occurring within 30 days, for patients undergoing a wide variety of both orthopaedic and non-orthopaedic surgical procedures. Registry data is prospectively collected on a continuous basis by trained reviewers. The data is routinely audited and has been demonstrated to have high inter-observer reliability.13 Patients undergoing revision total knee arthroplasty were identified using Current Procedural Terminology (CPT) codes 27486, 27487 and 27488. Patients who had an infectious etiology for revision TKA were excluded from this study. Infectious etiology was determined by ICD-9 and ICD-10 codes. Two patient cohorts were defined in this study: (1) patients with chronic preoperative steroid usage and (2) patients without chronic preoperative steroid usage. ACS-NSQIP defines chronic preoperative corticosteroid use as “patients who required regular administration of oral or parenteral corticosteroid medications in the 30 days before surgery for a chronic medical condition.”14 Patient demographics of interest and clinical characteristics collected included patient age, sex, race, and Body Mass Index (BMI), which was stratified according to the World Health Organization classification. Total length of stay (LOS), absence or severity of dyspnea, smoking history, preoperative functional status, type of anesthesia, and American Society of Anesthesiologists (ASA) class were also collected. Patient comorbidities and operative features collected included transfusion requirements, pulmonary comorbidities, cardiac comorbidities, renal failure, dialysis requirement, history of recent weight loss, bleeding disorder, ascites, and diabetes mellitus status. Recorded 30-day postoperative complications included superficial and deep surgical site infections (SSI), organ space infection, wound dehiscence, urinary tract infection, sepsis, septic shock, death, return to operating room, and extended hospital LOS. Extended hospital LOS was defined as > 7 days in the hospital postoperatively. In order to determine their association with chronic preoperative steroid use, data on patient demographics, comorbidities, and postoperative infectious complications were analyzed with univariate analysis using Pearson's Chi-squared test. Variables with p < 0.05 were selected for multivariate analysis. For multivariate analysis, binary logistic linear regression analysis was performed to determine whether chronic steroid was an independent risk factor for infectious complications, extended LOS, return to the operating room, and patient mortality. Multivariate analysis results were reported as odds ratios with 95% confidence intervals. A p-value of < 0.05 was used as the cutoff for significance.
Demographics
Steroid
No Steroid
474
10499
N
%
Sex Male 137 28.9% Female 337 71.1% Race White 351 74.1% Black or African American 78 16.5% Hispanic 24 5.1% American Indian or Alaska Native 11 2.3% Asian 8 1.7% Native Hawaiian or Pacific Islander 2 0.4% Anesthesia Type General 289 61.0% Regional 151 31.9% Monitored Anesthesia Care/ 34 7.2% Intravenous Sedation Diabetes Mellitus Status No Diabetes Mellitus 397 83.8% Non-Insulin-Dependent Diabetes 49 10.3% Mellitus Insulin-Dependent Diabetes 31 6.5% Mellitus American Association of Anesthesiologists Score 1 or 2 105 22.2% 3 or 4 369 77.8% Dyspnea Status No dyspnea 414 87.3% Moderate exertion 57 12.0% At rest 3 0.6% Functional Status Independent 440 92.8% Partially Dependent 33 7.0% Totally Dependent 1 0.2% History of Smoking 49 10.34% BMI 18.5–30 201 42.4% 30–34.9 104 21.9% 35–39.9 88 18.6% > 40 81 17.1% Age < 50 41 8.6% 51–60 107 22.6% 61–70 182 38.4% 71–80 108 22.8% 80+ 36 7.6%
N
%
4102 6397
39.1% 60.9%
8447 1401 463 52 97 39
80.5% 13.3% 4.4% 0.5% 0.9% 0.4%
6436 3293 770
61.3% 31.4% 7.3%
8301 1508
79.1% 14.4%
690
6.6%
4517 5982
43.0% 57.0%
9773 705 21
93.1% 6.7% 0.2%
10162 325 12 1240
96.8% 3.1% 0.1% 11.81%
3697 2957 2037 1808
35.2% 28.2% 19.4% 17.2%
845 2697 3702 2474 781
8.0% 25.7% 35.3% 23.6% 7.4%
p-value
< 0.001
< 0.001
0.971
0.016
< 0.001
< 0.001
< 0.001
0.33 0.004
0.506
Table 2 Comorbidities of patients undergoing revision total knee arthroplasty. Comorbidities
Steroid Use
No Steroid Use
3. Results
474
10499
3.1. Demographics
N
%
N
%
42 327 1 2 3 25 0 5
8.9% 69.0% 0.2% 0.4% 0.6% 5.3% 0.00% 1.1%
507 7025 4 32 25 355 2 38
4.8% 66.9% 0.0% 0.3% 0.2% 3.4% 0.02% 0.4%
Pulmonary Comorbidities Cardiac comorbidities Renal Failure Dialysis Weight loss Bleeding disorder Ascites Preoperative Transfusion
A total of 10,973 patients underwent rTKA and met inclusion criteria for the study. In total, 474 of the included patients were on preoperative steroid therapy (4.3%) and 10,499 patients (95.7%) were not. Patients on preoperative steroids were more likely to be female (p < 0.001), identify as non-white (p < 0.001), have a higher ASA class (p < 0.001), have dyspnea (p < 0.001), be less functionally independent (p < 0.001), and have a lower BMI (p = 0.004; Table 1).
p-value
< 0.001 0.347 0.085 0.654 0.096 0.027 0.764 0.018
bleeding disorder (p = 0.027), and require preoperative transfusion (p = 0.018) when compared to patients not on preoperative corticosteroid treatment (Table 2).
3.2. Comorbidities Patients on corticosteroid therapy were more likely to have a history of pulmonary disease (p < 0.001), be non-diabetic (p = 0.016), have a 174
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S.C. Fassihi, et al.
postoperative infectious complications following revision TKA. In our analysis, chronic corticosteroid use was not associated with an increased risk of surgical site infection after revision rTKA. This is consistent with previous work by Luessenhop et al., who retrospectively assessed various risk factors for periprosthetic joint infection (PJI) in patients undergoing primary total joint arthroplasty. They found that while corticosteroid use was a significant risk factor for PJI, it was not a significant risk factor when controlling for patients with rheumatoid arthritis on multiple regression analysis. This suggests that the condition for which the corticosteroids are being used, not the medication itself, may be responsible for any increases in infection risk seen in this patient population.23 In contrast to these findings, Salt et al. performed a retrospective, case-control analysis on 2212 patients undergoing primary total joint arthroplasty and found that prednisone was an independent risk factor for postoperative infection.24 Additionally, Somayaji et al. found that there is a dose-dependent effect of corticosteroids on infection risk, as only prednisone doses exceeding 15 mg/day were associated with increased risk of postoperative infection in patients with rheumatoid arthritis undergoing total joint arthroplasty.25 Lastly, in an ACS-NSQIP analysis of patients undergoing all-cause surgery from 2005 to 2008, Ismael et al. found that preoperative corticosteroid use was associated with increased risk of superficial SSI, deep SSI, organ/space SSI, wound dehiscence, and mortality.8 While the exact association between chronic preoperative steroid use and postoperative infection following total joint arthroplasty remains to be clearly elucidated, the present study adds to the growing body of evidence and is the first of its kind to focus on revision TKA. Our analysis found that chronic corticosteroid use was independently associated with increased rates of septic shock and extended hospital length of stay following rTKA. To the authors’ knowledge, these specific findings that have not been previously associated with chronic preoperative steroid use, even for other types of surgery. Increased rates of septic shock and extended LOS may be an indication that chronic steroid use reflects poorer underlying health, as these patients may be physiologically frailer and take longer to recover from surgery. This notion is corroborated by our findings that patients on preoperative steroids were more likely to have dyspnea, have a higher ASA status, and be less functionally independent. Given the extended LOS seen in these patients, clinicians should counsel these patients preoperatively on their risk of prolonged hospitalization following rTKA in order to appropriately set expectations. Additionally, postoperative infections should be managed in a more aggressive fashion to prevent progression to septic shock, as these patients are at an increased risk of this complication by virtue of their corticosteroid use. There were several limitations to this study. First, there are inherent limitations to the use of the ACS-NSQIP database. Dose, duration, and indications for chronic steroid therapy are not reported in this database, introducing the possibility that numerous variables may be confounding the findings. Additionally, only short-term complication rates can be analyzed, as the ACS-NSQIP database only tracks patients for the first 30 days postoperatively. It is plausible that continued corticosteroid use places the patients at greater risk of PJI beyond the immediate perioperative period, but this cannot be accounted for with the present data. Another limitation of all database studies is the use of CPT codes for research purposes. As CPT codes were initially developed for billing purposes, the utilization of these codes represents a potential confounding variable that cannot be accounted for. Reporting based on financial incentive can introduce coding bias that could theoretically include more minor procedures that are not truly rTKA. Furthermore, the possibility of human error in reporting of data is a limitation that pervades all database analyses. Lastly, a major limitation of retrospective research is the inability to show causality, as our study shows an association between chronic corticosteroid use and both septic shock and extended hospital LOS, but it cannot demonstrate a cause-and-effect relationship.
Table 3 Univariate analysis of association between chronic steroid use and postoperative complications in patients undergoing revision total knee arthroplasty. Complications
Superficial surgical site infection Deep Wound Infection Organ/Space Infection Wound Dehiscence Pneumonia Urinary tract Infection Sepsis Septic Shock Death Other Outcomes Extended Length of Stay (> 7 days) Return to Operating Room
Steroid
No Steroid
474
10499
p-value
N
%
N
%
1 4 4 2 3 6 4 3 3
0.2% 0.8% 0.8% 0.4% 0.6% 1.3% 0.8% 0.6% 0.6%
71 53 74 42 41 77 39 8 20
0.7% 0.5% 0.7% 0.4% 0.4% 0.7% 0.4% 0.1% 0.2%
0.220 0.315 0.724 0.941 0.414 0.191 0.107 < 0.001 0.039
26 14
5.5% 2.95%
275 332
2.6% 3.16%
< 0.001 0.799
3.3. Postoperative complications On univariate analysis, patients on preoperative steroids were significantly more likely to experience septic shock (0.6% vs 0.1%; p < 0.001), death (0.6% vs 0.2%; p = 0.039), and extended hospital LOS (5.5% vs 2.6%; p < 0.001; Table 3). Preoperative corticosteroid use was not associated with an increased risk of surgical site infections. On multivariate analysis, chronic corticosteroid use was an independent risk factor for septic shock (OR 6.174, 95% CI 1.422–26.812; p = 0.015) and extended hospital LOS (OR 1.572, 95% CI 1.025–2.415; p < 0.038; Table 4). 4. Discussion While the overall rate of revision after primary TKA remains low, the projected increase in demand for rTKA represents a potential healthcare burden. Furthermore, the mean total cost of an rTKA procedure has been increasing with time.15,16 Ong et al. found that patients undergoing rTKA were placed at a 5–6 times higher risk of needing a subsequent revision surgery relative to those undergoing primary TKA.17 Re-revisions present a major challenge both medically and financially. The potentially catastrophic impact on patients and significant resource burden on the healthcare system emphasizes the need to identify potential complications of rTKA and risk factors for them. Chronic corticosteroid use is a risk factor for poor wound healing and negative surgical outcomes,8,11,18,19 as chronic steroid use impairs vascular permeability, chemotaxis, leukocyte adhesion and phagocytosis, all of which are critical for tissue repair and defense against infection.11,20–22 Despite these known physiologic effects, there is a paucity of data on the effects of chronic corticosteroid use on infection rates following total joint arthroplasty. Previous studies of steroid use in the setting of arthroplasty have yielded mixed results and are confounded by the presence of inflammatory arthropathy in this subset of patients.23–25 To our knowledge, this is the first study to directly examine the relationship between chronic glucocorticoid use and Table 4 Multivariate analysis of postoperative complications associated with chronic steroid use on univariate analysis. Postoperative complication
Septic Shock Death Extended Length of Stay (> 7 days)
p-value
0.015 0.308 0.038
Odds Ratios
6.174 1.916 1.572
95% CI lower
higher
1.422 0.509 1.025
26.812 3.043 2.415
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5. Conclusion
2010;468. https://doi.org/10.1007/s11999-010-1308-6 2052–9. 6. Joint A, Registry R, Report A. American Joint Replacement Registry 2017 Annual Report Fourth AJRR Annual Report on Hip and Knee Arthroplasty Data. 2017; 2017. 7. Fuentes A, Pineda M, Venkata K. Comprehension of top 200 prescribed drugs in the US as a resource for pharmacy teaching, training and practice. Pharmacy. 2018;6:43. https://doi.org/10.3390/pharmacy6020043. 8. Ismael H, Horst M, Farooq M, Jordon J, Patton JH, Rubinfeld IS. Adverse effects of preoperative steroid use on surgical outcomes. Am J Surg. 2011;201:305–309. https://doi.org/10.1016/j.amjsurg.2010.09.018. 9. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids:A systematic review of the literature. Arch Surg. 2008;143:1222–1226. 10. Zarling BJ, Sikora-Klak J, Bergum C, Markel DC. How do preoperative medications influence outcomes after total joint arthroplasty? J Arthroplasty. 2017;32:S259–S262. https://doi.org/10.1016/j.arth.2017.04.031. 11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11:954–963. 12. van Zaane B, Nur E, Squizzato A, et al. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemostasis. 2010;8:2483–2493. https://doi.org/10.1111/j.1538-7836.2010. 04034.x. 13. Surgeons Ac of American College of Surgeons National Surgical Quality Improvement Program 2015:1–41. 14. National Surgical Quality Improvement Program. User Guide for 2012 ACS NSQIP Participant Use Data File. Chicago, IL: American College of Surgeons; 2013 Available at: https://www.facs.org/~/media/files/quality%20programs/nsqip/ug12.ashx. 15. Oduwole KO, Molony DC, Walls RJ, Bashir SP, Mulhall KJ. Increasing financial burden of revision total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2010;18:945–948. https://doi.org/10.1007/s00167-010-1074-8. 16. Kallala RF, Vanhegan IS, Ibrahim MS, Sarmah S, Haddad FS. Financial analysis of revision knee surgery based on NHS tariffs and hospital costs: does it pay to provide a revision service? Bone Joint Lett J. 2015;97–B:197–201. https://doi.org/10.1302/ 0301-620X.97B2.33707. 17. Ong KL, Lau E, Suggs J, Kurtz SM, Manley MT. Risk of subsequent revision after primary and revision total joint arthroplasty. Clin Orthop Relat Res. 2010;468:3070–3076. https://doi.org/10.1007/s11999-010-1399-0. 18. Ginzler E, Diamond H, Kaplan D, Weiner M, Schlesinger M, Seleznick M. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum. 1978;21:37–44. 19. Everhart JS, Andridge RR, Scharschmidt TJ, Mayerson JL, Glassman AH, Lemeshow S. Development and validation of a preoperative surgical site infection risk score for primary or revision knee and hip arthroplasty. J Bone Joint Surg Am. 2016;98:1522–1532. https://doi.org/10.2106/JBJS.15.00988. 20. Greaves MW. Anti-inflammatory action of corticosteroids. Postgrad Med. 1976;52:631–633. 21. Jamal A, Homa DM, O'Connor E, et al. Current cigarette smoking among adults — United States, 2005–2014. MMWR Morb Mortal Wkly Rep. 2015;64:1233–1240. https://doi.org/10.15585/mmwr.mm6444a2. 22. Anstead GM. Steroids, retinoids, and wound healing. Adv Wound Care. 1998;11:277–285. 23. Luessenhop C, Higgins L, Brause B, Ranawat C. Multiple prosthetic infections after total joint arthroplasty. J Arthroplasty. 1996;11(7):862–868. https://doi.org/10. 1016/S0883-5403(96)80189-6. 24. Salt E, Wiggins AT, Rayens MK, et al. Moderating effects of immunosuppressive medications and risk factors for post-operative joint infection following total joint arthroplasty in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 2017;46(4):423–429. https://doi.org/10.1016/j.semarthrit.2016.08.011. 25. Somayaji R, Barnabe C, Martin L. Risk factors for infection following total joint arthroplasty in rheumatoid arthritis. Open Rheumatol J. 2013;7:119–124. https://doi. org/10.2174/1874312920131210005 Published 2013 Nov 29.
In this large national database analysis, chronic corticosteroid use was found to be independently associated with septic shock and extended hospital LOS following revision TKA. Notably, there was no increase in surgical site infections with chronic preoperative steroid use. Surgeons should counsel these patients on their increased risk of requiring an extended hospitalization following rTKA in order to appropriately set expectations. Furthermore, if these patients develop signs or symptoms of infection, clinicians should have a low threshold for aggressive treatment in order to prevent progression to septic shock. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of competing interest The authors of this manuscript certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patentlicensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) directly related to the subject matter or materials discussed in this manuscript. Acknowledgements None. References 1. Mistry JB, Elmallah RK, Chughtai M, Oktem M, Harwin SF, Mont MA. Long-term survivorship and clinical outcomes of a single radius total knee arthroplasty. Surg Technol Int. 2016;28:247–251. 2. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Jt Surg - Ser A. 2007;89:780–785. https://doi.org/10.2106/JBJS.F.00222. 3. Khan M, Osman K, Green G, Haddad FS. The epidemiology of failure in total knee arthroplasty. Bone Joint Lett J. 2016;98–B:105–112. https://doi.org/10.1302/0301620X.98B1.36293. 4. Pugely AJ, Martin CT, Gao Y, Schweizer ML, Callaghan JJ. The incidence of and risk factors for 30-day surgical site infections following primary and revision total joint arthroplasty. J Arthroplasty. 2015;30:47–50. https://doi.org/10.1016/j.arth.2015.01. 063. 5. Mortazavi SMJ, Schwartzenberger J, Austin MS, Purtill JJ, Parvizi J. Revision total knee arthroplasty infection: incidence and predictors. Clin Orthop Relat Res.
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