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Solid Organ Transplant Patients Experience High Rates of Infection and Other Complications After Total Knee Arthroplasty
The Journal of Arthroplasty 28 (2013) 960–963
Contents lists available at SciVerse ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Solid Organ Transplant Patients Experience High Rates of Infection and Other Complications After Total Knee Arthroplasty Brian A. Klatt MD a, G. Daxton Steele MD b, Catherine J. Fedorka MD c, Alvaro I. Sánchez MD/MS d, Antonia F. Chen MD/MBA a, Lawrence S. Crossett MD a a b c d
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania OrthoWilmington, Wilmington, North Carolina Hahnemann University Hospital, Philadelphia, Pennsylvania Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
a r t i c l e
i n f o
Article history: Received 6 March 2012 Accepted 6 February 2013 Keywords: total knee arthroplasty solid organ transplant infections complications
a b s t r a c t Survival after solid organ transplants in the United States is increasing, and there is a need to understand the complications in knee arthroplasty patients who underwent organ transplantation. A retrospective study was conducted from 1993–2008 on 19 patients (23 knee arthroplasties) with previous successful solid organ transplants. Eleven knee arthroplasties were performed after renal transplantation, and 12 after nonrenal solid organ transplant (seven liver, four heart, one lung). Complications occurred in 9/23 patients (39.1%) and infections occurred in 4/23 patients (17.3%). Of the infected knees, two had MRSA, one had MSSA, and one Escherichia coli. Noninfectious complications (5/24, 21.7%) include aseptic loosening, quadriceps rupture, femoral fracture, hemarthrosis, and arthrofibrosis. All patients with complications were on immunosuppressant medications at the time of arthroplasty. There was a significantly higher rate of infection in the renal group compared to the non-renal group (P = 0.022). There was also a higher overall complication rate in the renal group however this did not reach significance. © 2013 Elsevier Inc. All rights reserved.
The number of solid organ transplants in the United States is steadily increasing. Data from the 2008 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients show an upward trend in most types of solid organ transplants from 1997 to 2006 [1] (Fig. 1 A-B). In addition, these data also reflect an increase in organ survival for most types of transplants [1]. The success of organ transplant can be attributed to a number of medical advancements. Patient selection and surgical technique have improved, and better immunosuppression medications, such as cyclosporine and tacrolimus, have increased the success rates of solid organ transplants. Corticosteroids, most often prednisone, remain an important component of the antirejection medications that most of these patients will take as lifelong regimens [2]. Now that these patients are surviving longer, there will be an everincreasing population of patients with transplants who will need total knee arthroplasty (TKA). The need for TKA in the transplant population is often a result of two different processes. The first process, osteonecrosis (ON), is most likely the result of chronic steroid usage. Long-term steroid use to prevent
The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2013.02.005. Reprint requests: Brian A. Klatt, MD, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 5230 Centre Avenue, Suite 415, Pittsburgh, PA 15232. 0883-5403/2806-0017$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.arth.2013.02.005
organ rejection predisposes this population to an increased risk of ON. This is predominantly seen in the femoral head, but it can also occur in the femoral condyle of the knee. The exact incidence of ON in the femoral condyle is not well defined in the literature. The second process, osteoarthritis, is becoming more prevalent as transplant patients survive longer. The overall success rate of transplant surgeries allows these patients to live longer and develop osteoarthritis, which may require treatment [3,4]. In addition to these two main causes of TKA, there are other issues in the transplant population. Poor metabolic function can give rise to osteoporosis and fragility fractures. Also, underlying systemic diseases, such as rheumatoid arthritis and lupus, contribute to both organ failure and joint destruction. Once these patients develop orthopaedic diseases, there is very little evidence to guide proper treatment strategies. ON of the hip and subsequent THA in this population have been evaluated in numerous studies [5–14]. Several studies report on TKA in post-transplant patients, although TKAs are apparently performed much less frequently in transplant patients than THA [15–17]. A recent literature review by Sayed-Noor [18] examined 9 studies of joint arthroplasties other than hips (Table 1). Eight of these studies involved TKA with a total of 51 total knees studied. The largest of these studies had 16 knees in 12 patients. Of the 51 knees, there was only one reported infection. Furthermore, very few complications were reported. Although other studies reported low complication and infection rates, sample sizes were limited and there was little focus on total knee
B.A. Klatt et al. / The Journal of Arthroplasty 28 (2013) 960–963
Number of Kidney Transplants
961
Number of Liver Transplants
Kidney-Deceased Donor
Liver-Deceased Donor
Kidney-Living Donor
Liver-Living Donor 286
6,428 4,409
361
6,227
91 5,836
7,898
A 1998
8,287
2002
2006
4,692
4,269
10,216
B 1998
2002
2006
Fig. 1. (A–B) Histograms demonstrate that over the past 12 years, the number of (A) kidney transplants and (B) liver transplants has been steadily increasing. The increase has been seen in both living and deceased donor types.
arthroplasty. Given the high transplant rate in our unique patient population in our geographic location, we conducted a study looking at complications, specifically infections, in knee arthroplasty patients who underwent successful solid organ transplants. Thus, the purposes of our study were (1) to identify the complications experienced by knee arthroplasty patients with solid organ transplants, and (2) to determine the incidence of infection rates in these patients. Materials and Methods We retrospectively reviewed all patients undergoing knee arthroplasty after solid organ transplantation at our institution from 1993 to 2008; patients with less than two year follow-up from knee arthroplasty after solid organ transplantation were excluded. We included patients who underwent TKA, unicondylar knee arthroplasty (UKA), and revision total knee arthroplasty (TKR) at our institution. Our institution treats a high volume of solid organ transplants, given our reputation as a transplant center. The orthopaedic department serves as the main referral center in the area for the treatment of ON
and osteoarthritis of the hip and knee in these transplant patients. Nine patients had 11 knee arthroplasties performed after renal transplantation (including 1 patient who underwent concurrent kidney and liver transplants), and 10 patients had 12 knee arthroplasties performed after nonrenal solid organ transplant (seven liver, four heart, one lung). All of the renal transplant patients underwent primary TKA. The non-renal transplant group underwent 7 TKAs, 2 UKAs, and 3 TKRs. The median age of the patients at arthroplasty was 60 years (percentile range, 48–68 years). There were 9 men and 10 women. The median time from transplant until arthroplasty was 3.8 years (range, 1.2–22.6 years). The average follow-up was7.1 years (range 2.3–17.4 years). No patients were recalled specifically for this study; all data were obtained from medical records and radiographs. The records were pulled from a combination of 2 sources. The first source was medical records, as the medical center computer archival system was used to recover operative reports, discharge summaries, laboratory results, radiology reports, and microbiology reports. Charts were reviewed when available; however, the policy at our institution is to destroy charts
Table 1 Summary of the Results of Joint Arthroplasties (Other Than the Hip) in Solid Organ Transplants.
Study
Number of Arthroplasties
Indication and Time (mo) Post-Transplant for Arthroplasty
Mean Age or Age (yr) at Arthroplasty
Mean Follow-Up (mo)
Outcome
Maguire et al [17] Bradford et al [5]
5 knees 10 knees (6 patients) 3 shoulder (2 patients)
Osteonecrosis N/A Osteonecrosis 42 (10–175)
N/A 34 (16–56)
N/A 12-108
Isono et al [9] Papagelopoulos et al [21]
2 knees (1 patient) 2 knees (2 patients)
34 39, 64
34 (3–105) 36-72
Tannenbaum et al [20]
4 knees (3 patients)
43, 45, 46, 67
12-120
Testa et al [14] Levitsky et al [16]
4 knees 8 knees (5 patients) 1 ankle (1 patient)
Osteonecrosis, (38) Osteonecrosis, (48) Posttraumatic OA, (39) Osteonecrosis, supracondylar fracture, OA (36–72) N/A 53 (39–70) Osteonecrosis. OA (23–74)
N/A 44 (39–59)
N/A 50 (3–114)
N/A Kettle-kamp Knee score: (37 ?? 72) Shoulder; No pain Near normal function N/A Knee Society Score (45.5 → 94) Hospital for Special Surgeries Knee score N/A N/A
Sperling et al [22]
5 shoulders (4 patients)
55 (41–79)
65 (26-202
Modified Neer rating
Boquet et al [15]
16 knees (12 patients)
Osteonecrosis. Malunion, OA, 42 (6–71) Osteonecrosis. OA, RA 132 (10–294)
58 (32–70)
65 (25–107)
Knee Society Scores = 97.1 (93–100)
Complications None Conversion of uni- to total knee prosthesis (n = 1) Pin extrusion (n = 1) Stiffness (n = 1) None None PE wear (n = 1) Infection → death (n = 1) None No major complications Mild wound bleeding (n = 1) Superior subluxation (n = 1) Glenoidal radiolucency (n-1) Scar necrosis (n = 1)
Mo: Months, yr: Years, N/A: Not Available, OA: Osteoarthritis, RA: Rheumatoid Arthritis. (Reproduced with permission from the open access article: Sayed-Noor AS. Joint arthroplasties other than the hip in solid organ transplant recipients. Open Orthop J. 2009;3:27–31.)
962
B.A. Klatt et al. / The Journal of Arthroplasty 28 (2013) 960–963
Table 2 Non-Infectious Complications After Total Knee Arthroplasty in Solid Organ Transplant Patients. Non-Infectious Complications
#
Operative Intervention
Instability and Pain Quadriceps rupture Femur fracture Hemarthrosis Arthrofibrosis
1 1 1 1 1
Conversion to constrained polyethylene Primary repair, mersilene tape augment ORIF Irrigation and debridement Open debridement
*ORIF = open reduction and internal fixation.
that have been inactive for over 10 years. The second source was our transplant registry. Our transplant registry keeps accurate records of the medications and transplant related issues. They were able to provide us with a list of medications taken by patients throughout the study period. IRB approval was obtained prior to initiating this study. The diagnosis at the time of surgery was collected from the operative reports. Twelve of the TKAs were done for osteoarthritis, 5 for osteonecrosis, and one for history of a previously septic native knee. Both of the UKAs were done for osteoarthritis. One of the TKRs was done for an infected primary TKA and 2 were revised for aseptic loosening. Demographic characteristics, type of immunosuppression therapy at time of joint surgery, and complications requiring further knee surgery after index arthroplasty were collected via hospital records review and transplant registry. Immunosuppression schedules were tailored to each individual. At the time of TKA, ten of the 11 knees in the renal transplant group were on immunosuppressant medications and one was on hemodialysis secondary to transplant failure, while all 12 knees in the nonrenal solid organ transplantation group were on immunosuppressant medications. At the time of follow-up, four of 11 renal transplant patients had failed their transplants, as they were on hemodialysis and three of the non-renal patients had transplant rejections with two requiring a second transplant. All transplants and TKAs were performed at a single institution by the two attendings (BAK and LSC). Patient postoperative regimens all differed and were determined by the transplant medicine team. Upon discharge, patients were seen in follow-up at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and yearly. Infections were defined according to the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infections, where every patient had positive culture documentation [19]. Variables were analyzed descriptively. Relative frequencies (percentages) were calculated using as denominator the total number of knee arthroplasty procedures. After the description of the total number of knee arthroplasty procedures, patients were categorized according to the type of transplant surgery into two groups, renal transplant group and nonrenal transplant group. We assessed the overall rate of complications, the rate of infection-related complications, and the rate of noninfection complications separately. Comparisons between renal transplant and nonrenal transplant groups were performed using unpaired t-tests or Mann–Whitney tests in continuous variables, and chi-square tests or Fisher's exact tests were performed for categorical variables. Analyses were performed in Stata (Version 11) software (StataCorp LP, College Station, TX). Results Nine of the 23 knee arthroplasties (39.1%) presented with one or more complications. Noninfectious complications (5/23, 21.7%) included chronic pain and swelling that underwent a two stage revision 5 days apart with a negative infection workup (one), quadriceps rupture treated with primary repair and augmentation with Mersilene tape (Ethicon, Inc, Somerville, NJ) (one), femoral stress fracture treated with ORIF (one), hemarthrosis treated with irrigation and débridement (one), and arthrofibrosis requiring open débridement (one) (Table 2). Although there were more overall
complications (6/11) in the renal group than in the nonrenal group (3/12) the difference as not statistically significant (P = 0.147). The infection rate was four of 24 (17.3%). Two of the infections occurred in the same patient on contralateral knees and the patient had methicillin-resistant Staphylococcus aureus in both. The patient required two-stage revision with explantation and placement of antibiotic spacer on one primary TKA, and the contralateral side had a failure of two-stage reimplantation, had repeat two-stage reimplantation, and was placed on lifelong antibiotics. Two of the infections were diagnosed at 2 and 3 weeks and treated with irrigation and débridement with polyethylene exchange. Of these two, one had methicillin-sensitive S aureus, and one had Escherichia coli (Table 3). All infections were suppressed with the patients maintaining a functioning TKA. There was a significant difference (P = 0.022) between infections in the renal transplant group (4/11) and in the non-renal transplant group (0/12). All of the complications were in patients on immunosuppressant medications. All patients not only were on immunosuppressants at the time of initial arthroplasty but also at the time of complication. As only one patient was not on immunosuppressant medications at the time of knee arthroplasty it is difficult to compare the two groups. No correlation (P = 0.769) was found between the number of immunosuppressant medications taken between each group at the time of the knee arthroplasty and the rate of complication. Discussion The rates of renal and other solid organ transplants are continuing to rise [1]. Not only are more procedures being performed, but these transplant patients are also living longer after transplantation [1]. These patients often have multiple medical comorbidities and remain on a mix of immunosuppressive drugs post-operatively to prevent organ rejection. The combination of immunosuppression and complex medical histories seem to predispose patients to complications and infections in elective procedures, such as knee arthroplasty. In this study, we (1) identified the complications experienced by knee arthroplasty patients with solid organ transplants and (2) determined the incidence of infection rates in these patients. Numerous studies have shown efficacy and safety with THA performed after solid organ transplant [5–14]. A recent literature review by Sayed-Noor [18] suggested good to excellent results in transplant patients that had joint arthroplasty excluding total hip arthroplasty. Boquet et al [15] examined 12 renal transplant patients with 16 TKAs and found no complications. Despite these findings, many authors suggest a theoretical concern for higher infection rates and complication rates, due to immunosuppression, poor bone stock, and medical comorbidities. Only one study conducted by Tannenbaum et al [20] demonstrated a high complication and infection rate in a study containing 33 THAs/bipolar and four TKAs in patients with a renal or liver transplantation, which documented a 27% overall complication rate and 14% infection rate. The complication (39.1%) and infection (17.3%) rates are higher in our study than in comparative studies in the literature. There were 23
Table 3 Organisms in Each if the Four Infections and the Definitive Treatment. Infections
#
Operative Intervention
Acute (MSSA), 24 days post-op
1
Acute (E coli), 16 days post-op
1
Chronic (MRSA) Chronic recurrent (MRSA)
1 1
Irrigation and debridement, polyethylene exchange Irrigation and debridement, polyethylene exchange Two-stage replant Two-stage replant, chronic suppressive antibiotics
MSSA = methicillin-sensitive S aureus; MRSA = methicillin-resistant S aureus.
B.A. Klatt et al. / The Journal of Arthroplasty 28 (2013) 960–963
knee arthroplasties in 19 patients in our study, which is a larger sample than any of the previously mentioned studies. Our study was performed at a tertiary care center, and it is possible our cohort represents a patient population with more medical comorbidities. This is one possible explanation for the higher rate of complications and infections. A dedicated transplant registry provided a thorough database of solid organ transplant information. Current studies are underway at our institution to evaluate the total number of arthroplasties performed on all transplant patients, which would give us a better understanding of what proportion the patients in this study represents. There are several drawbacks to the design of this preliminary study. First, this is a retrospective study, and data were collected from chart review. However, the data from the transplant registry were very complete as they were gathered prospectively. There was clear documentation of the drugs and the time periods they were used. Second, we had no patient outcome measures, such as SF-12 and Knee Society Scores. Our future plans include studying this patient population prospectively with outcome measures. Third, our sample size is small, although this is the largest series of knee arthroplasty in transplant patients in the literature we could identify. With small numbers and varied immunosuppression regimens, it is difficult to reach conclusions with regard to which subgroups are at highest risk for issues. Medication regimens continue to change and are tailored to individual patients. A mass mailing to the entire transplant registry is planned to expand our numbers. Despite these limitations, we believe the findings in our study are worth reporting, as this is the largest series of solid organ transplant patients that have undergone knee arthroplasty. Caution should be exercised in transplant patients undergoing knee arthroplasty. Preoperative discussions with the patient and their transplant caretakers are important. Every available measure should be taken to prevent infections and complications, as we believe this is truly a high-risk group of patients.
Acknowledgments The authors thank Dr. Jay Irrgang for statistical support and Alma Heyl for her work as research coordinator.
963
References 1. US Department of Health and Human Services. 2008 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998–2007. Rockville, MD: US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2008. 2. Sakai T, Sugano N, Kokado Y, et al. Tacrolimus may be associated with lower osteonecrosis rates after renal transplantation. Clin Orthop Relat Res 2003;415:163. 3. Bia M. Evaluation and management of bone disease and fractures post transplant. Transplant Rev (Orlando) 2008;22:52. 4. Heaf JG. Bone disease after renal transplantation. Transplantation 2003;75:315. 5. Bradford DS, Janes PC, Simmons RS, et al. Total Hip Arthroplasty in Renal Transplant Recipients. Clin Orthop Relat Res 1983;181:107. 6. Bucci JR, Oglesby RJ, Agodoa LY, et al. Hospitalizations for Total Hip Arthroplasty after Renal Transplantation in the United States. Am J Transplant 2002;2:999. 7. Cheng EY, Klibanoff JE, Robinson HJ, et al. Total Hip Arthroplasty with Cement after Renal Transplantation. J Bone Joint Surg Am 1995;77:1535. 8. Goffin E, Baertz G, Rombouts JJ. Long-term survivorship analysis of cemented total hip replacement (THR) after avascular necrosis of the femoral head in renal transplant recipients. Nephrol Dial Transplant 2006;21:784. 9. Isono SS, Woolson ST, Schurman DJ. Total joint arthroplasty for steroid-induced osteonecrosis in cardiac transplant patients. Clin Orthop Relat Res 1987;217:201. 10. Murzic WJ, McCollum DE. Hip arthroplasty for osteonecrosis after renal transplantation. Clin Orthop Relat Res 1994;299:212. 11. Nowicki P, Chaudhary H. Total hip replacement in renal transplant patients. J Bone Joint Surg Br 2007;89:1561. 12. Panpayiotis PJ, Hay JE, Galanis EC, et al. Total Joint Arthroplasty in Orthotopic Liver Transplant Recipients. J Arthroplasty 1996;11(8):889. 13. Shrader MW, Schall D, Parvizi J, et al. Total Hip Arthroplasty in Patients With Renal Failure: a Comparison Between Transplant and Dialysis Patients. J Arthroplasty 2006;21(3):324. 14. Testa G, Goldstein RM, Toughanipour A, et al. Guidelines for surgical procedures after liver transplantation. Ann Surg 1998;227(4):590. 15. Boquet J, Goffin E, Poilvache P. Outcome of total knee arthroplasties after renal transplantation. Arch Orthop Trauma Surg 2008;128:1345. 16. Levitsky J, Te HS, Cohen SM. The safety and outcome of joint replacement surgery in liver transplant recipients. Liver Transpl 2003;9:373. 17. Maguire WB, Muscio P, Dodd PA. The results of joint replacement surgery in renal transplant patients. Aust N Z J Surg 1981;51:534. 18. Sayed-Noor AS. Joint arthroplasties other than the hip in solid organ transplant recipients. Open Orthop J 2009;3:27. 19. Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 2011;469(11):2992. 20. Tannenbaum DA, Matthews LS, Grady-Benson JC. Infection around joint replacements in patients who have a renal or liver transplantation. J Bone Joint Surg Am 1997;79:36. 21. Papagelopoulos PJ, Hay JE, Galanis EC, Morrey BF. Total joint arthroplasty in orthotopic liver transplant liver transplant recipients. J Arthroplasty 1996;11(8):889. 22. Sperling JW, Cofield RH. Case reports: shoulder arthroplasty in transplant recipients: a report of five cases. Clin Orthop Relat Res 2006;442:273.
Contents lists available at SciVerse ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Solid Organ Transplant Patients Experience High Rates of Infection and Other Complications After Total Knee Arthroplasty Brian A. Klatt MD a, G. Daxton Steele MD b, Catherine J. Fedorka MD c, Alvaro I. Sánchez MD/MS d, Antonia F. Chen MD/MBA a, Lawrence S. Crossett MD a a b c d
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania OrthoWilmington, Wilmington, North Carolina Hahnemann University Hospital, Philadelphia, Pennsylvania Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
a r t i c l e
i n f o
Article history: Received 6 March 2012 Accepted 6 February 2013 Keywords: total knee arthroplasty solid organ transplant infections complications
a b s t r a c t Survival after solid organ transplants in the United States is increasing, and there is a need to understand the complications in knee arthroplasty patients who underwent organ transplantation. A retrospective study was conducted from 1993–2008 on 19 patients (23 knee arthroplasties) with previous successful solid organ transplants. Eleven knee arthroplasties were performed after renal transplantation, and 12 after nonrenal solid organ transplant (seven liver, four heart, one lung). Complications occurred in 9/23 patients (39.1%) and infections occurred in 4/23 patients (17.3%). Of the infected knees, two had MRSA, one had MSSA, and one Escherichia coli. Noninfectious complications (5/24, 21.7%) include aseptic loosening, quadriceps rupture, femoral fracture, hemarthrosis, and arthrofibrosis. All patients with complications were on immunosuppressant medications at the time of arthroplasty. There was a significantly higher rate of infection in the renal group compared to the non-renal group (P = 0.022). There was also a higher overall complication rate in the renal group however this did not reach significance. © 2013 Elsevier Inc. All rights reserved.
The number of solid organ transplants in the United States is steadily increasing. Data from the 2008 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients show an upward trend in most types of solid organ transplants from 1997 to 2006 [1] (Fig. 1 A-B). In addition, these data also reflect an increase in organ survival for most types of transplants [1]. The success of organ transplant can be attributed to a number of medical advancements. Patient selection and surgical technique have improved, and better immunosuppression medications, such as cyclosporine and tacrolimus, have increased the success rates of solid organ transplants. Corticosteroids, most often prednisone, remain an important component of the antirejection medications that most of these patients will take as lifelong regimens [2]. Now that these patients are surviving longer, there will be an everincreasing population of patients with transplants who will need total knee arthroplasty (TKA). The need for TKA in the transplant population is often a result of two different processes. The first process, osteonecrosis (ON), is most likely the result of chronic steroid usage. Long-term steroid use to prevent
The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2013.02.005. Reprint requests: Brian A. Klatt, MD, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 5230 Centre Avenue, Suite 415, Pittsburgh, PA 15232. 0883-5403/2806-0017$36.00/0 – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.arth.2013.02.005
organ rejection predisposes this population to an increased risk of ON. This is predominantly seen in the femoral head, but it can also occur in the femoral condyle of the knee. The exact incidence of ON in the femoral condyle is not well defined in the literature. The second process, osteoarthritis, is becoming more prevalent as transplant patients survive longer. The overall success rate of transplant surgeries allows these patients to live longer and develop osteoarthritis, which may require treatment [3,4]. In addition to these two main causes of TKA, there are other issues in the transplant population. Poor metabolic function can give rise to osteoporosis and fragility fractures. Also, underlying systemic diseases, such as rheumatoid arthritis and lupus, contribute to both organ failure and joint destruction. Once these patients develop orthopaedic diseases, there is very little evidence to guide proper treatment strategies. ON of the hip and subsequent THA in this population have been evaluated in numerous studies [5–14]. Several studies report on TKA in post-transplant patients, although TKAs are apparently performed much less frequently in transplant patients than THA [15–17]. A recent literature review by Sayed-Noor [18] examined 9 studies of joint arthroplasties other than hips (Table 1). Eight of these studies involved TKA with a total of 51 total knees studied. The largest of these studies had 16 knees in 12 patients. Of the 51 knees, there was only one reported infection. Furthermore, very few complications were reported. Although other studies reported low complication and infection rates, sample sizes were limited and there was little focus on total knee
B.A. Klatt et al. / The Journal of Arthroplasty 28 (2013) 960–963
Number of Kidney Transplants
961
Number of Liver Transplants
Kidney-Deceased Donor
Liver-Deceased Donor
Kidney-Living Donor
Liver-Living Donor 286
6,428 4,409
361
6,227
91 5,836
7,898
A 1998
8,287
2002
2006
4,692
4,269
10,216
B 1998
2002
2006
Fig. 1. (A–B) Histograms demonstrate that over the past 12 years, the number of (A) kidney transplants and (B) liver transplants has been steadily increasing. The increase has been seen in both living and deceased donor types.
arthroplasty. Given the high transplant rate in our unique patient population in our geographic location, we conducted a study looking at complications, specifically infections, in knee arthroplasty patients who underwent successful solid organ transplants. Thus, the purposes of our study were (1) to identify the complications experienced by knee arthroplasty patients with solid organ transplants, and (2) to determine the incidence of infection rates in these patients. Materials and Methods We retrospectively reviewed all patients undergoing knee arthroplasty after solid organ transplantation at our institution from 1993 to 2008; patients with less than two year follow-up from knee arthroplasty after solid organ transplantation were excluded. We included patients who underwent TKA, unicondylar knee arthroplasty (UKA), and revision total knee arthroplasty (TKR) at our institution. Our institution treats a high volume of solid organ transplants, given our reputation as a transplant center. The orthopaedic department serves as the main referral center in the area for the treatment of ON
and osteoarthritis of the hip and knee in these transplant patients. Nine patients had 11 knee arthroplasties performed after renal transplantation (including 1 patient who underwent concurrent kidney and liver transplants), and 10 patients had 12 knee arthroplasties performed after nonrenal solid organ transplant (seven liver, four heart, one lung). All of the renal transplant patients underwent primary TKA. The non-renal transplant group underwent 7 TKAs, 2 UKAs, and 3 TKRs. The median age of the patients at arthroplasty was 60 years (percentile range, 48–68 years). There were 9 men and 10 women. The median time from transplant until arthroplasty was 3.8 years (range, 1.2–22.6 years). The average follow-up was7.1 years (range 2.3–17.4 years). No patients were recalled specifically for this study; all data were obtained from medical records and radiographs. The records were pulled from a combination of 2 sources. The first source was medical records, as the medical center computer archival system was used to recover operative reports, discharge summaries, laboratory results, radiology reports, and microbiology reports. Charts were reviewed when available; however, the policy at our institution is to destroy charts
Table 1 Summary of the Results of Joint Arthroplasties (Other Than the Hip) in Solid Organ Transplants.
Study
Number of Arthroplasties
Indication and Time (mo) Post-Transplant for Arthroplasty
Mean Age or Age (yr) at Arthroplasty
Mean Follow-Up (mo)
Outcome
Maguire et al [17] Bradford et al [5]
5 knees 10 knees (6 patients) 3 shoulder (2 patients)
Osteonecrosis N/A Osteonecrosis 42 (10–175)
N/A 34 (16–56)
N/A 12-108
Isono et al [9] Papagelopoulos et al [21]
2 knees (1 patient) 2 knees (2 patients)
34 39, 64
34 (3–105) 36-72
Tannenbaum et al [20]
4 knees (3 patients)
43, 45, 46, 67
12-120
Testa et al [14] Levitsky et al [16]
4 knees 8 knees (5 patients) 1 ankle (1 patient)
Osteonecrosis, (38) Osteonecrosis, (48) Posttraumatic OA, (39) Osteonecrosis, supracondylar fracture, OA (36–72) N/A 53 (39–70) Osteonecrosis. OA (23–74)
N/A 44 (39–59)
N/A 50 (3–114)
N/A Kettle-kamp Knee score: (37 ?? 72) Shoulder; No pain Near normal function N/A Knee Society Score (45.5 → 94) Hospital for Special Surgeries Knee score N/A N/A
Sperling et al [22]
5 shoulders (4 patients)
55 (41–79)
65 (26-202
Modified Neer rating
Boquet et al [15]
16 knees (12 patients)
Osteonecrosis. Malunion, OA, 42 (6–71) Osteonecrosis. OA, RA 132 (10–294)
58 (32–70)
65 (25–107)
Knee Society Scores = 97.1 (93–100)
Complications None Conversion of uni- to total knee prosthesis (n = 1) Pin extrusion (n = 1) Stiffness (n = 1) None None PE wear (n = 1) Infection → death (n = 1) None No major complications Mild wound bleeding (n = 1) Superior subluxation (n = 1) Glenoidal radiolucency (n-1) Scar necrosis (n = 1)
Mo: Months, yr: Years, N/A: Not Available, OA: Osteoarthritis, RA: Rheumatoid Arthritis. (Reproduced with permission from the open access article: Sayed-Noor AS. Joint arthroplasties other than the hip in solid organ transplant recipients. Open Orthop J. 2009;3:27–31.)
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Table 2 Non-Infectious Complications After Total Knee Arthroplasty in Solid Organ Transplant Patients. Non-Infectious Complications
#
Operative Intervention
Instability and Pain Quadriceps rupture Femur fracture Hemarthrosis Arthrofibrosis
1 1 1 1 1
Conversion to constrained polyethylene Primary repair, mersilene tape augment ORIF Irrigation and debridement Open debridement
*ORIF = open reduction and internal fixation.
that have been inactive for over 10 years. The second source was our transplant registry. Our transplant registry keeps accurate records of the medications and transplant related issues. They were able to provide us with a list of medications taken by patients throughout the study period. IRB approval was obtained prior to initiating this study. The diagnosis at the time of surgery was collected from the operative reports. Twelve of the TKAs were done for osteoarthritis, 5 for osteonecrosis, and one for history of a previously septic native knee. Both of the UKAs were done for osteoarthritis. One of the TKRs was done for an infected primary TKA and 2 were revised for aseptic loosening. Demographic characteristics, type of immunosuppression therapy at time of joint surgery, and complications requiring further knee surgery after index arthroplasty were collected via hospital records review and transplant registry. Immunosuppression schedules were tailored to each individual. At the time of TKA, ten of the 11 knees in the renal transplant group were on immunosuppressant medications and one was on hemodialysis secondary to transplant failure, while all 12 knees in the nonrenal solid organ transplantation group were on immunosuppressant medications. At the time of follow-up, four of 11 renal transplant patients had failed their transplants, as they were on hemodialysis and three of the non-renal patients had transplant rejections with two requiring a second transplant. All transplants and TKAs were performed at a single institution by the two attendings (BAK and LSC). Patient postoperative regimens all differed and were determined by the transplant medicine team. Upon discharge, patients were seen in follow-up at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and yearly. Infections were defined according to the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infections, where every patient had positive culture documentation [19]. Variables were analyzed descriptively. Relative frequencies (percentages) were calculated using as denominator the total number of knee arthroplasty procedures. After the description of the total number of knee arthroplasty procedures, patients were categorized according to the type of transplant surgery into two groups, renal transplant group and nonrenal transplant group. We assessed the overall rate of complications, the rate of infection-related complications, and the rate of noninfection complications separately. Comparisons between renal transplant and nonrenal transplant groups were performed using unpaired t-tests or Mann–Whitney tests in continuous variables, and chi-square tests or Fisher's exact tests were performed for categorical variables. Analyses were performed in Stata (Version 11) software (StataCorp LP, College Station, TX). Results Nine of the 23 knee arthroplasties (39.1%) presented with one or more complications. Noninfectious complications (5/23, 21.7%) included chronic pain and swelling that underwent a two stage revision 5 days apart with a negative infection workup (one), quadriceps rupture treated with primary repair and augmentation with Mersilene tape (Ethicon, Inc, Somerville, NJ) (one), femoral stress fracture treated with ORIF (one), hemarthrosis treated with irrigation and débridement (one), and arthrofibrosis requiring open débridement (one) (Table 2). Although there were more overall
complications (6/11) in the renal group than in the nonrenal group (3/12) the difference as not statistically significant (P = 0.147). The infection rate was four of 24 (17.3%). Two of the infections occurred in the same patient on contralateral knees and the patient had methicillin-resistant Staphylococcus aureus in both. The patient required two-stage revision with explantation and placement of antibiotic spacer on one primary TKA, and the contralateral side had a failure of two-stage reimplantation, had repeat two-stage reimplantation, and was placed on lifelong antibiotics. Two of the infections were diagnosed at 2 and 3 weeks and treated with irrigation and débridement with polyethylene exchange. Of these two, one had methicillin-sensitive S aureus, and one had Escherichia coli (Table 3). All infections were suppressed with the patients maintaining a functioning TKA. There was a significant difference (P = 0.022) between infections in the renal transplant group (4/11) and in the non-renal transplant group (0/12). All of the complications were in patients on immunosuppressant medications. All patients not only were on immunosuppressants at the time of initial arthroplasty but also at the time of complication. As only one patient was not on immunosuppressant medications at the time of knee arthroplasty it is difficult to compare the two groups. No correlation (P = 0.769) was found between the number of immunosuppressant medications taken between each group at the time of the knee arthroplasty and the rate of complication. Discussion The rates of renal and other solid organ transplants are continuing to rise [1]. Not only are more procedures being performed, but these transplant patients are also living longer after transplantation [1]. These patients often have multiple medical comorbidities and remain on a mix of immunosuppressive drugs post-operatively to prevent organ rejection. The combination of immunosuppression and complex medical histories seem to predispose patients to complications and infections in elective procedures, such as knee arthroplasty. In this study, we (1) identified the complications experienced by knee arthroplasty patients with solid organ transplants and (2) determined the incidence of infection rates in these patients. Numerous studies have shown efficacy and safety with THA performed after solid organ transplant [5–14]. A recent literature review by Sayed-Noor [18] suggested good to excellent results in transplant patients that had joint arthroplasty excluding total hip arthroplasty. Boquet et al [15] examined 12 renal transplant patients with 16 TKAs and found no complications. Despite these findings, many authors suggest a theoretical concern for higher infection rates and complication rates, due to immunosuppression, poor bone stock, and medical comorbidities. Only one study conducted by Tannenbaum et al [20] demonstrated a high complication and infection rate in a study containing 33 THAs/bipolar and four TKAs in patients with a renal or liver transplantation, which documented a 27% overall complication rate and 14% infection rate. The complication (39.1%) and infection (17.3%) rates are higher in our study than in comparative studies in the literature. There were 23
Table 3 Organisms in Each if the Four Infections and the Definitive Treatment. Infections
#
Operative Intervention
Acute (MSSA), 24 days post-op
1
Acute (E coli), 16 days post-op
1
Chronic (MRSA) Chronic recurrent (MRSA)
1 1
Irrigation and debridement, polyethylene exchange Irrigation and debridement, polyethylene exchange Two-stage replant Two-stage replant, chronic suppressive antibiotics
MSSA = methicillin-sensitive S aureus; MRSA = methicillin-resistant S aureus.
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knee arthroplasties in 19 patients in our study, which is a larger sample than any of the previously mentioned studies. Our study was performed at a tertiary care center, and it is possible our cohort represents a patient population with more medical comorbidities. This is one possible explanation for the higher rate of complications and infections. A dedicated transplant registry provided a thorough database of solid organ transplant information. Current studies are underway at our institution to evaluate the total number of arthroplasties performed on all transplant patients, which would give us a better understanding of what proportion the patients in this study represents. There are several drawbacks to the design of this preliminary study. First, this is a retrospective study, and data were collected from chart review. However, the data from the transplant registry were very complete as they were gathered prospectively. There was clear documentation of the drugs and the time periods they were used. Second, we had no patient outcome measures, such as SF-12 and Knee Society Scores. Our future plans include studying this patient population prospectively with outcome measures. Third, our sample size is small, although this is the largest series of knee arthroplasty in transplant patients in the literature we could identify. With small numbers and varied immunosuppression regimens, it is difficult to reach conclusions with regard to which subgroups are at highest risk for issues. Medication regimens continue to change and are tailored to individual patients. A mass mailing to the entire transplant registry is planned to expand our numbers. Despite these limitations, we believe the findings in our study are worth reporting, as this is the largest series of solid organ transplant patients that have undergone knee arthroplasty. Caution should be exercised in transplant patients undergoing knee arthroplasty. Preoperative discussions with the patient and their transplant caretakers are important. Every available measure should be taken to prevent infections and complications, as we believe this is truly a high-risk group of patients.
Acknowledgments The authors thank Dr. Jay Irrgang for statistical support and Alma Heyl for her work as research coordinator.
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