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How Do Previous Solid Organ Transplant Recipients Fare After Primary Total Knee Arthroplasty?
The Journal of Arthroplasty xxx (2015) 1e7
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Original article
How Do Previous Solid Organ Transplant Recipients Fare After Primary Total Knee Arthroplasty? Mitchell R. Klement, MD *, Colin T. Penrose, BA, BS, Abiram Bala, BA, Samuel S. Wellman, MD, Michael P. Bolognesi, MD, Thorsten M. Seyler, MD, PhD Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 August 2015 Received in revised form 26 September 2015 Accepted 2 October 2015 Available online XXX
Introduction: Total knee arthroplasty (TKA) has been proven to increase knee outcome scores after solid organ transplantation (SOT), but many authors are concerned about a higher complication rate. The purpose of this study is to evaluate the complication profile of TKA after previous SOT. Methods: A search of the entire Medicare database from 2005 to 2011 was performed using International Classification of Disease, version 9, codes to identify 3339 patients who underwent TKA after 1 or more solid organ transplants including the kidney (2321), liver (772), lung (129), heart (412), and pancreas (167). A cohort of 1,685,295 patients served as a control with minimum 2-year follow-up. Postoperative complications at 30-day, 90-day, and overall time points were compared between the 2 cohorts. Results: Patients with any SOT were younger (age: <65, odds ratio [OR]: 6.58, P < .001), male (OR: 1.88, P < .001), and medically complex (significant increase in 28 of 29 Elixhauser comorbidities, P < .05). There was a significant increase (P < .05) in 11 of 13 (84.6%) recorded postoperative medical complications rates at 90 days. There was a significant increase overall in periprosthetic infection (OR: 2.11, P < .001), periprosthetic fracture (OR: 1.78, P < .001), and TKA revision (OR: 1.36, P < .001). When analyzed by individual organ, heart and lung transplants carried the fewest medical and surgical complications. Conclusion: The results of this study demonstrate that patients with previous SOT who undergo elective primary TKA have more postoperative complications in the global period and at short-term follow-up. Yet, complication profiles by individual organ varied significantly. © 2015 Elsevier Inc. All rights reserved.
Keywords: primary knee arthroplasty total knee replacement solid organ transplant complications transplantation
Since 2003 at least 25,000 solid organ transplants (SOTs) have been performed annually in the United States, with 27,036 completed in 2014. While this number has reached a plateau because of organ availability, evolutions in procurement, implantation technique, and posttransplant immunosuppression have dramatically increased recipient survivorship. The majority of organ transplants were in patients aged >50 years, and with the exception of lung and intestine transplantation, 5-year survival rates for this age group average 70% [1]. Small retrospective cohort studies have
Investigation was performed at the Duke University Medical Center, Durham, NC. No funding was provided for this study. One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2015.10.007. * Reprint requests: Mitchell R. Klement, MD, Duke University Medical Center, Department of Orthopaedic Surgery, Box 3000, Durham, NC 27710. http://dx.doi.org/10.1016/j.arth.2015.10.007 0883-5403/© 2015 Elsevier Inc. All rights reserved.
shown that total knee arthroplasty (TKA) in patients with a prior SOT is a worthwhile endeavor as the rate patient reported good/ excellent outcomes after kidney, liver, and lung transplantation ranges from 92% to 100% [2]. In addition, Knee Society scores in these patients were significantly increased after TKA compared to preoperative values (Knee Society score, kidney: 51.2-89.2, liver: 55.0-93.8, and lung: 58.2-92; all P < .05) [2]. Promising results have also been shown in prior cardiac and lung transplant recipients with 100% good/excellent patient-reported outcomes in lung patients at final follow-up [3,4]. However, given the need for continued immunosuppression and increased medical comorbidities, many authors have cited concerns regarding increased infection and other postoperative complications in this patient population [5-7]. As perioperative and postoperative complications will be linked to surgeon and hospital reimbursement, little is known about complication profiles in this patient population in the global period (first 90-days after surgery) and at short-term follow-up. Furthermore earlier reports of TKA in SOT patients focused on the treatment of steroid-induced osteonecrosis [8], while the majority of transplant patients undergoing TKA today are for
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M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
treatment of end-stage osteoarthritis[8,9]. Many of the studies reporting outcomes in total joint arthroplasty and solid organ transplantation to date have been limited by a small number of patients [3,8,9]. A majority of the literature has also focused on TKA in kidney and liver transplantation, but kidney transplants have been decreasing for the past 3 years, whereas lung and heart transplants are on the rise [1]. In addition, to achieve adequate numbers, collection for these studies often spans decades, during which significant advances in the fields of transplant and arthroplasty have occurred [10-14] The purpose of this study was to use a large national database to identify patients undergoing TKA after various SOTs with a specific focus on postoperative complications. A large national database study would also enable comparison between individual organ transplant types to control to see if one fares worse than the others. We hypothesize that SOT recipients in general will have an increased postoperative complication profile compared to controls, and the individual organ complication profiles will vary. Methods A retrospective review of a Medicare database was conducted from 2005 to 2011 containing 100% of inpatient and 100% of outpatient administrative records using Pearl Diver technologies (Warsaw, IN). This study was exempt from institutional review board approval at our institution as deidentified patient data were reviewed. All patients who underwent TKA were included and identified using both the corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code 81.54 and Current Procedural Terminology codes 27445, 27446, and 27447. By looking at distinct patient volumes, patients with bilateral TKA and total hip arthroplasty were excluded. Using the Pearl Diver Boolean command language, the ICD-9 diagnosis code for the relevant SOTs (Kidney V42.0, Heart V42.1, Lung V42.6, Liver V42.7, Pancreas V42.83) was used to identify the cohort of patients who carried these diagnoses before the date of their primary TKA. The control group was defined as patients who did not carry a diagnosis of these SOTs before their primary TKA. Using relevant ICD-9-CM and Current Procedural Terminology codes, the rates of various postoperative complications that occurred within 30 days, within 90 days, and overall were evaluated. Minimum 2-year follow-up was required for inclusion. Comorbidities of the various groups were identified based on the Elixhauser comorbidity index and relevant ICD-9 diagnosis codes (Appendix 1). Standard bivariate descriptive statistics were performed to compare both the comorbidity and complication rates. A chi-squared test was used to compare categorical variables, and a 2-sided Fisher exact test was used for categorical variables with decreased incidence (<0.01%). P < .05 indicated statistical significance.
younger age versus the control cohort (age: <65, OR: 6.58, 95% CI: 6.15-7.06, P < .001, Table 1). Patient Comorbidities Not surprisingly, the transplant cohort as a whole represented a medically more complex population with a statistically significant increase (P < .05) in 28 of 29 Elixhauser medical comorbidities. Notable medical comorbidities more prevalent in this group not related to transplantable end-organ failure included peripheral vascular disease (P ¼ .001), rheumatoid arthritis (P ¼ .001), lymphoma (P ¼ .001), and metastatic cancer (P ¼ .001). Conditions related to transplantable organ failure were also increased such as diabetes (P ¼ .001), chronic obstructive pulmonary disease (P ¼ .001), congestive heart failure (P ¼ .001), and renal failure (P ¼ .001). Furthermore, these complications were also significant across all individual transplant groups. In addition, the transplant cohort overall was more likely to smoke, abuse alcohol, abuse drugs, and carry psychiatric diagnosis of depression (all P < .001). The only medical comorbidity that was not significant was prevalence of peptic ulcer disease (P ¼ .592). Postoperative Medical Complications The transplant cohort overall had a statistically significant increase (P < .05) of 11 of the 13 (84.6%) recorded postoperative medical complications at both the 30- and 90-day time points compared to controls with the exception of stroke. The incidence of pulmonary embolism (PE) was statistically decreased overall in the SOT cohort compared to controls (OR: 0.69, 95% CI: 0.49-0.98, P ¼ .041, Fig. 1). When separated into individual organ at the 30-day time point, lung and heart transplants appeared to have the most favorable complication profile after TKA as only 6 of 13 medical complications were statistically increased, followed by pancreas (7 of 13), liver (7 of 13), and kidney (8 of 13, P < .05, Fig. 1). With regard to 90-day time point, pancreas transplant was the safest with 6 of 15 medical complications being significantly increased, followed by lung (7 of 13), liver (8 of 13), heart (9 of 13), and kidney (10 of 13, Table 2). Acute renal failure (ARF) was the only complication that remained significant (P < .05) across each individual organ at 30 and 90 days postoperatively (Fig. 1, Table 2). Postoperative Surgical Complications The transplant cohort overall had a statistically significant increase (P < .05) of 6 of the 10 recorded acute postoperative surgical Table 1 Patient Demographics.
Results
Control
Patient Demographics From 2005 to 2011 1,685,295 Medicare patients underwent TKA without a prior sold organ transplant. In the same time period, a total of 3334 patients who had prior surgical organ transplant underwent primary TKA. There were 2321 kidney transplants, 772 liver transplants, 129 lung transplants, 412 heart transplants, and 167 pancreas transplants patients. The average duration of followup for the control cohort was 4.02 years, and the average follow-up for the combined SOT cohort was 3.52 years. There were a higher percentage of males undergoing TKA with an SOT than in the control group (50.1% vs 34.8%, odds ratio [OR]: 1.88, 95% CI: 1.752.01, P < .001). In addition, transplant patients underwent TKA at a
Gender Female Male Unknown Age (y) <65 65-69 70-74 75-79 80-84 85 Unknown Total cohort size
Prior SOT
N
%
N
%
1,074,440 587,958 33,832
63.75 34.89 2.01
1629 1673 51
48.86 50.18 1.53
164,055 457,278 431,912 367,631 220,725 84,502 33,832 1,685,295
9.73 27.13 25.63 21.81 13.10 5.01 2.01
1385 799 623 386 130 42 51 3334
41.54 23.97 18.69 11.58 3.90 1.26 1.53
SOT, solid organ transplantation.
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
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Fig. 1. Forest plot comparing medical complications at 30 days between the combined solid organ transplant cohort and the control. Blue lines indicate that the complication is significantly reduced in the combined solid organ transplant (SOT) cohort, black lines indicate no statistical difference, and red lines indicate that the complication is statistically increased in the combined SOT cohort. DVT, deep venous thrombosis; MI, myocardial infarction; OR, odds ratio; PE, pulmonary embolus; PNA, pneumonia; SIRS, systemic inflammatory response syndrome.
complications at 30-day time point compared to controls including bleeding complications (OR: 1.89, 95% CI: 1.55-2.32, P < .001), wound complications (OR: 2.31, 95% CI: 1.76-3.02, P < .001), cellulitis/seroma (OR: 1.71, 95% CI: 1.47-2.00, P < .001), periprosthetic joint infection (PJI; OR: 2.07, 95% CI: 1.53-2.68, P < .001), and need for irrigation and debridement (OR: 1.83, 95% CI: 1.442.32, P < .001). When analyzed by individual organ at 30 days postoperatively, heart had the fewest complications (2 of 10) followed by lung (3 of 10), pancreas (5 of 10), kidney (5 of 10), and liver (7 of 10). The most striking result was the significant risk of periprosthetic fracture in the heart (OR: 35.66, 95% CI: 14.57-87.30, P < .001) and lung (OR: 35.65, 95% CI: 11.36-85.64, P < .001) cohorts. In addition, only heart had no increased risk of periprosthetic infection (P ¼ .242). At 90 days postoperatively, heart transplant patients had the fewest surgical complications (2 of 7), followed by kidney (3 of 7), pancreas (4 of 7), lung (5 of 7), and liver (5 of 7) with the periprosthetic fracture risk still drastically higher in heart (OR: 8.87, 95% CI; 2.86-20.95, P < .001) and lung (OR: 29.18, 95% CI: 9.3070.05, P < .001) recipients (Table 3). At final follow-up (overall time point), the combined SOT cohort had significantly increase in 5 of 6 recorded surgical complications including PJI (OR: 2.11, 95% CI: 1.82-2.49, P < .001), periprosthetic fracture (OR: 1.78, 95% CI; 1.352.35, P < .001), need for revision (OR; 1.36, 95% CI; 1.14-1.62, P ¼ .001), need for irrigation and debridement (OR; 2.07, 95% CI: 1.772.41, P < .001), and extensor mechanism rupture (OR: 1.69, 95% CI: 1.16-2.46, P ¼ .005). Only patellar complications were not significantly increased (P ¼ .92, Fig. 2). Individually, lung and heart
transplant had an increase in 2 of 6 complications, followed by pancreas (3 of 6), kidney (4 of 6), and lung (4 of 6, Table 4). Discussion Since the first kidney transplant in Boston, 1954, solid organ transplantation has been called a miracle of the 20th century [15]. The recognition of acute rejection and the development of immunosuppressive medications have significantly increased organ survival; however, lifelong immunosuppression carries a dangerous side effect profile [16]. In the first year after kidney transplantation, 11.7% will die from infection, another 10.1% from new malignant neoplasms, and 30.1% from cardiovascular disease as a result [17]. Another complication of immunosuppression unique to orthopedics is the risk of bone disease and osteoporosis. A recent review of Taiwan’s National Health database found a significant increase in osteoporosis (hazard ratio [HR]: 5.14, CI: 3.13-8.43) and osteoporosis-related fractures (HR: 5.76, 95% CI: 3.80-8.74) compared to controls. When analyzed by individual SOT, they found the highest incidence of osteoporosis in the lung transplant cohort (HR: 191.4), followed by heart (HR: 8.40), liver (HR: 9.68), and kidney (HR: 3.40) transplant recipients [18]. While the diagnosis of osteoporosis and fragility fractures was not evaluated the study herein, the authors did find a statistically significant increase in the periprosthetic fracture rate (OR: 1.78, P < .001) overall without an increase in patellar complications. This complication was particularly prominent in heart and lung transplant patients,
4
Table 2 Medical Complications at 90 Days by Individual Organ. 90-Day Complication (Medical)
Control All SOT IN (%)
CI
Liver
P Value IN (%) OR
CI
P Value IN (%)
2.310 1.38 1.10-1.73 .005 10.410 1.92 1.71-2.14 <.001 9.120 1.21 1.07-1.36 .001
2.240 1.34 1.01-1.76 .037 10.340 1.9 1.66-2.17 <.001 8.400 1.1 0.95-1.28 .168
17.520 1.15 1.05-1.26
17.230 1.13 1.01-1.26
.001
2.010 2.47 1.94-3.15 <.001 5.160 0.960 0.930 4.620 2.880 15.060
1.61 0.69 1.20 2.27 3.97 5.52
1.38-1.88 0.49-0.98 0.84-1.71 1.93-2.67 3.24-4.87 4.99-6.10
<.001 .041 1.23 <.001 <.001 <.001
Lung OR
CI
Heart
P Value IN (%) OR
CI
2.720 6.350 7.900
1.63 1.05-2.52 1.12 0.83-1.49 1.03 0.79-1.34
.025 .442 .784
0.001 2.35 0.75-5.65 0.001 0.66 0.21-1.59 13.180 1.83 1.10-3.05
.068 .068 .018
.023
13.990
0.88 0.72-1.08
.24
22.480 0.21 0.09-1.66
<.001
1.810 2.22 1.64-3.02 <.001
1.680
2.06 1.19-3.58
.008
5.040 0.820 0.950 4.520 2.890 15.550
1.57 0.59 1.22 2.22 3.98 6.03
1.31-1.90 0.37-0.93 0.80-1.86 1.82-2.70 3.12-5.08 5.39-6.78
<.001 .022 .341 <.001 <.001 <.001
5.050% 0.001 0.001 4.020 3.240 13.470
1.58 0.46 0.83 1.96 4.48 5.1
1.14-2.18 1.52-1.09 0.27-1.95 1.36-2.81 3.01-6.68 4.15-6.27
.005 .88 1.00 <.001 <.001 <.001
0.001 4.87 1.55-11.67 0.001 0.001 0.001 8.530 0.001 13.180
1.19 2.89 5.16 4.37 5.4 4.97
Pancreas
P Value IN (%) OR
.004
0.38-2.87 .616 0.92-6.94 .033 1.64-12.38 .003 2.35-8.11 <.001 1.72-12.96 .003 2.98-8.28 <.001
CI
3.160 1.9 1.09-3.30 17.480 3.5 2.71-4.51 12.140 1.67 1.24-2.24 19.900 1.35 1.06-1.722 2.670 3.31 1.82-6.03 5.340 0.001 0.001 6.800 3.160 19.660
1.67 0.88 1.57 3.41 4.37 8.02
1.09-2.57 0.28-2.07 0.50-3.70 2.32-5.01 2.51-7.59 6.29-10.23
P Value IN (%) OR
CI
P Value
.02 <.001 .001
0.001 1.8 0.57-4.29 8.980 1.63 0.96-2.77 7.780 1.02 0.57-1.78
.211 .068 .944
.014
12.570 0.78 0.49-1.23
.293
<.001
0.001 3.72 1.19-8.88
.013
.017 1.00 .258 <.001 <.001 <.001
6.590 0.001 0.100 0.001 0.001 7.780
2.09 2.21 3.95 1.44 4.14 2.76
1.13-3.86 .015 0.71-5.28 .081 1.26-9.52 .01 0.46-3.44 .406 1.32-9.86 .008 1.57-4.87 <.001
28.850 1.22 1.13-1.32 <.001
28.440 1.2
1.10-1.32 <.001
30.700
1.34 1.15-1.57 <.001
27.130 1.13 0.76-1.66
.53
28.160 1.19 0.96-1.47
.109
31.140 1.37 0.99-1.90
.056
30.680 1.42 1.32-1.53 <.001
30.720 1.43 1.31-1.57 <.001
31.990
1.52 1.31-1.77 <.001
29.460 1.35 0.92-1.97
.116
26.940 1.19 0.96-1.48
.108
31.140 1.46 1.05-2.03
.021
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; MI, myocardial infarction; Afib, atrial fibrillation; DVT, deep venous thrombosis; OR, odds ratio; PE, pulmonary embolus; PNA, pneumonia; SIRS, systemic inflammatory response syndrome.
Table 3 Surgical Complications at 90 Days by Individual Organ. 90-Day Complication (Surgical)
Control All SOT
Kidney
IN (%)
IN (%) OR
CI
MUA Periprosthetic infection Periprosthetic fracture TKA revision Arthrotomy/I&D Patellar complications Extensor mechanism rupture
1.020 0.960
0.720 0.70 2.340 2.48
0.47-1.05 .089 1.98-3.11 <.001
0.600 0.592 0.35-1.00 .048 2.630 2.79 2.17-3.61 <.001
0.001 0.63 0.20-1.49 2.460 2.61 2.65-4.12
0.140
0.001 1.08
0.35-2.84
.812
0.001 1.56
0.50-3.65
0.001 4.71 1.52-11.07
.005
0.001 29.18 9.30-70.05 <.001
0.450 1.250 0.190
0.720 1.6 2.400 1.93 0.001 0.80
1.07-2.39 .021 1.55-2.41 <.001 0.26-1.87 .84
0.730 1.62 2.630 2.12 0.001 1.15
1.01-2.62 .043 1.64-2.74 <.001 0.37-2.69 .63
0.001 1.44 0.46-3.37 2.200 1.77 1.09-2.86 0.001 3.47 1.12-8.16
.408 .018 .016
0.001 0.001 0.000
0.180
0.001 0.813 0.26-1.90
0.001 1.16
0.37-2.73
0.001 3.52 1.14-8.27
.015
P Value IN (%) OR
.839
Liver CI
P Value IN (%) OR
.26
.625
Lung CI
Heart
P Value IN (%) OR .468 <.001
0.000 0.001
CI
0.00 0.00-2.29 4.18 1.33-10.02
P Value IN (%) OR .645 .008
Pancreas CI
0.001 1.19 0.38-2.81 0.001 1.27 0.41-2.99
P Value IN (%) OR .618 .605
CI
0.001 3.00 0.96-7.16 0.001 3.20 1.02-7.62
P Value .029 .023
0.001 8.89 2.86-20.95 <.001
0.000 0.00 0.00-13.11 1.00
8.9 2.14-28.35 <.001 3.17 1.01-7.61 .024 0.00 0.00-12.54 1.00
0.001 2.71 0.87-6.38 0.001 0.96 0.31-2.27 0.000 0.00 0.00-3.89
.04 1.00 1.00
0.001 6.81 2.18-16.24 .001 0.001 2.43 0.77-5.78 .06 0.000 0.00 0.00-9.66 1.00
0.001 21.82 6.95-52.36 <.001
0.000 0.00 0.00-3.95
1.00
0.000 0.00 0.00-9.80
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; MUA, manipulation under anesthesia; OR, odds ratio; TKA, total knee arthroplasty; I&D, irrigation and debridement.
1.00
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
MI 1.680 Heart failure 5.710 Arrhythmia 7.640 without Afib Arrhythmia 15.52 with Afib Respiratory 0.820 failure DVT 3.250 PE 1.370 Stroke 0.770 PNA 2.090 Sepsis/SIRS 0.740 Acute renal 2.960 failure Postoperative 24.750 anemia Blood 23.580 transfusion
Kidney
IN (%) OR
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
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Fig. 2. Forest plot comparing surgical complications at overall time point between the combined solid organ transplant cohort and the control. Black lines indicate no statistical difference compared to the control cohort and red lines indicate that the complication is statistically increased in the combined SOT cohort. I&D, irrigation and debridement; TKA, total knee arthroplasty.
correlating with the higher osteoporosis rates found in the Taiwan National database. All SOTs at our institution receive tacrolimus (adjusted to levels) and mycophenolate for the life of the graft if no complications, rejections, or cancers occur. However, heart and lung transplants receive additional steroid at the time of transplantation (methylprednisolone, with additional dose for double lung transplant) and basiliximab, an antibody to the IL-2 receptor of T cells. While the effect of these medications on bone metabolism is conflicting [19,20], patients with chronic lung and heart disease are at increased risk because of physical inactivity, chronic medications, poor nutrition, and smoking status [21]. In addition, among patients awaiting SOT, end-stage lung failure patients had the poorest pretransplant bone mineral density when measured on X-ray absorptiometry compared to liver, kidney, and heart [21]. Furthermore, immunosuppressive medications likely account for the significant increase in wound complications, cellulitis and seroma, and PJI. A similar infection rate was reported by Shaikh [22] in which 1 of 12 patients (8.33%) undergoing spinal surgery after SOT developed an infection. However, general, vascular, and plastic surgeries have reported few to no infectious complications in this patient population undergoing subsequent procedures [23-25]. In addition to being chronically immunosuppressed, the combined SOT cohort represents a medically complex group with significantly increased comorbidities at baseline using the Elixhauser Comorbidity Index. This index has been proven to be a superior measure of patient discrimination for multiple diseases in North America [26,27] and has also been proven to more accurately predict short-term outcomes after operations in general surgery
patients [28]. It should not be surprising then that a more medically complex cohort also had a statistically significant increase in every postoperative medical complication with the exception of stroke and PE (which were significantly decreased). The overall incidence of PE in the control cohort was 1.37% compared to 0.96% in the transplant cohort. However, when analyzed by individual organ, only kidney had a decreased incidence of PE (OR: 0.59, 95% CI: 0.370.93, P ¼ .22), whereas the other organs were not statistically significant (P > .05) and lung was significantly increased (OR: 2.89, 95% CI: 0.92-6.94, P ¼ .033). Patients with solid organ transplantation are considered to be at high risk for venous thromboembolism events as corticosteroids diminish fibrinolysis and calcineurin inhibitors are thought to be prothrombotic [29]. The most common venous thromboembolism prophylactic agent after total joint arthroplasty, enoxaparin, is excreted by the kidneys and the diminished reserve of the transplanted organ, and high incidence of acute renal injury in these patients after total joint arthroplasty may elevate the therapeutic levels of this agent resulting in fewer PEs [30]. Despite type of organ transplanted, acute kidney injury appeared to be the most common postoperative medical complication as this was statistically significant at all time points, consistent with prior study by Ledford et al [2] who saw 25%-50% complication rate in 21 TKAs, with most common complication being ARF. “Calcineurin inhibitor nephrotoxicity” is a welldescribed complication of this type of immunosuppressive agent and likely accounts for the increased risk of acute kidney injury seen overall and in each individual organ transplant in the present study [31,32]. A recent search of the Nationwide Inpatient Sample
1.00 0.000 0.00 0.00-3.62 .057 0.001 2.45 0.79-5.78
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; TKA, total knee arthroplasty; I&D, irrigation and debridement.
.001 0.001 8.06 2.57-19.08 .443 0.42-3.05 0.001 1.3 .057 0.780 1.56 0.98-2.48 .005 0.840 1.69 1.16-2.46 0.64
0.001 1.03 0.33-2.46 .817 8.980 3.78 2.22-6.42 <.001 0.001 4.97 1.59-11.86 .004 .038 .157 .192 4.610 1.62 1.02-2.56 3.640 1.44 0.86-2.42 0.000 0.00 0.00-1.17 .428 .286 1.00 0.001 1.35 0.43-3.24 0.001 1.45 0.49-3.70 0.000 0.00 0.00-3.78 3.710 1.29 1.04-1.60 .02 5.600 2.27 1.90-2.71 <.001 43.560 1.11 0.68-1.83 .653 3.900 1.36 1.14-1.62 .001 5.130 2.07 1.77-2.41 <.001 44.660 1.02 0.66-1.57 .92 2.90 2.54 0.62
4.400 1.54 1.09-2.17 .013 4.920 1.98 1.43-2.74 <.001 0.001 1.05 0.34-2.46 .816
.015 0.001 3.55 1.13-8.46 .413 0.001 1.41 0.45-3.32 .005 0.001 4.64 1.48-11.13 .007 1.380 1.61 1.13-2.28 1.530 1.78 1.35-2.36 <.001 0.86
2.070 2.43 1.48-3.99 <.001
0.001 1.12 0.36-2.68 5.580 2.15 1.41-3.28 <.001 .401 0.001 1.47 0.46-3.52 5.960 2.31 1.71-3.11 <.001 5.820 2.25 1.89-2.68 <.001 5.490 2.11 1.82-2.49 <.001 2.67
Periprosthetic Infection Periprosthetic fracture TKA revision Arthrotomy/I&D Patellar complications Extensor mechanism rupture
CI P Value IN (%) OR IN (%)
IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
Pancreas Heart Lung Liver Kidney Control All SOT
Overall Complication (Surgical)
Table 4 Surgical Complications at Overall Time Point by Individual Organ.
.807
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
P Value
6
database was performed by Cavanaugh et al [33] showed similar results. They identified patients with history of transplant and joint arthroplasty (primary or revision) from 1993 to 2011, with a specific focus on in-hospital complications. They found kidney transplant increased risk of systemic infection (OR: 2.85), deep venous thrombosis (OR: 2.07), ARF (OR: 3.48), and respiratory (OR: 1.34) and cardiac (OR: 1.21) complications. Liver transplant was associated with respiratory complications (OR: 1.68), cardiac complications (OR: 1.34), and ARF (OR: 4.48). Other transplants grouped together (including lung, bone marrow, and pancreas) were associated with wound complications (OR: 2.13), respiratory complications (OR: 2.06), and ARF (OR: 4.42). Similar results were seen in the present study but extended out to the 30- and 90-day time points. This may be worrisome as patients may still be at increased risk of medical complications after discharge. Furthermore, complications such as DVT and PE typically occur 20-30 days postoperatively and may not be adequately captured but examining only in-house complication profiles [34]. In addition, the rate of postoperative complications in the present study varied drastically compared to previously published data. Blood transfusion rates in our study were 30% in the postoperative period after SOT compared to 80% rate of transfusion reported previously after TKA in SOT patients [2]. Accurate reporting of this complication is particularly important, as blood transfusions have been individually associated with increased PJI [35]. PE was previously reported to be 1.7% after SOT and was 0.9% in our study [5]. Angermeier et al [5] reported a periprosthetic infection rate of 22% in 9 TKA patients, compared to 5.3% overall in our series, with no increased risk in lung and pancreas transplants. Their overall revision rate was 22% (2 of 9) compared to 3.9% in our series. Finally, Klatt et al [10] previously found no difference when comparing overall complications in renal transplants (11 knees) versus nonrenal transplants (12 knees, P ¼ .147) but did show an increased infection rate in the renal cohort (P ¼ .022). The discrepancies between the existing literature and the present study are likely attributed to a significantly larger sample size and perhaps a more representative patient population. Many of the previous studies are isolated to single, large, tertiary academic centers, whereas the data herein represent a nationwide sample. Strengths of this study include the utilization of a large, Medicare database to achieve an adequate sample size to statistically and accurately report complications rates of TKA after renal, liver, lung, heart, and pancreas transplantation. The nationwide sample provides the ability to compare the SOT group overall, as well as individual organ, to a large control cohort. To the authors’ knowledge, this is the first study to compare comorbidities, medical complications, and surgical complications between individual organ transplants for TKA after SOT. Limitations of a large database study include the potential for confounding variables that are available for analysis, including surgical implant, surgical technique, and type of surgical implant used. Surgical variables unique to transplantation were not available such as the dose and duration of immunosuppression and the nature of the graft (single vs double lung, cadaver versus livingrelated donor). The quality of the data soles relies on accurate coding at the time of patient encounter. This data were gathered from the Medicare database and may not apply to all patients or those from different countries. Pearl Diver technologies enable analysis of complications in the global period (first 90 days after surgery) and at short-term follow-up, data lacking from previous large-database studies investigating this topic. However, the cost of using this technology and the Medicare database standard analytical files is that each standard analytical file form is not available for individual review. Variables such as age, gender, comorbidities, and complications are counted from the coding and cannot be matched.
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
Furthermore, advanced statistics such as multivariate analysis cannot be performed to eliminate confounding variables. Finally, knee outcome scores, postoperative function, and patient satisfaction were not recorded in this database. This study suggests that overall SOT patients undergoing TKA are more likely to be male, younger, and have more medical comorbidities than traditional knee arthroplasty candidates. When combined SOT patients have significantly increased medical and surgical complications after their total knee arthropalsty surgery but at lower rates than traditionally reported, potentially due to increased patient cohorts. However, this study proves that not all individual transplants have a similar complication profiles, and special consideration should be given to renal and liver transplant patients as they are more at risk. The authors recommend a multidisciplinary approach to the care of these patients with early involvement of medical and transplant services. Regional anesthesia, multimodal pain therapy, and an enhanced recovery protocol may be necessary to limit postoperative complications. In addition, heart and lung patients had a lower complication profile than the overall liver, pancreas, and kidney cohorts. Conclusion In conclusion, the extensive reporting of medical and surgical complications after individual organ transplant in the present study will allow arthroplasty surgeons to better council their patients on the risks of knee arthroplasty surgery and ensure proper care perioperatively. This is also a significant reference for complication profiles in the “bundle-of-care” and outcome-based payment era. References 1. Annual Data Report of the US Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). Introduction. Am J Transplant 2013;13(Suppl 1):8. 2. Ledford CK, Watters TS, Wellman SS, et al. Risk versus reward: total joint arthroplasty outcomes after various solid organ transplantations. J Arthroplasty 2014;29(8):1548. 3. Isono SS, Woolson ST, Schurman DJ. Total joint arthroplasty for steroid-induced osteonecrosis in cardiac transplant patients. Clinical Orthop Relat Res 1987;217:201. 4. Ledford CK, Watters TS, Wellman SS, et al. Outcomes of primary total joint arthroplasty after lung transplantation. J Arthroplasty 2014;29(1):11. 5. Angermeier EW, Demos HA, Del Schutte H, et al. Complications of hip and knee joint replacement in solid-organ transplant patients. J Surg Orthop Adv 2013;22(3):204. 6. Vergidis P, Lesnick TG, Kremers WK, et al. Prosthetic joint infection in solid organ transplant recipients: a retrospective case-control study. Transpl Infect Dis 2012;14(4):380. 7. Papagelopoulos PJ, Hay JE, Galanis E, et al. Infection around joint replacements in patients who have a renal or liver transplantation (79-A: 36-43, Jan. 1997), Tannenbaum et al. J Bone Joint Surg Am 1998;80(4):607. 8. Maguire WB, Muscio P, Dodd PA. The results of joint replacement surgery in renal transplant patients. Aust N Z J Surg 1981;51(6):534. 9. Papagelopoulos PJ, Hay JE, Galanis EC, et al. Total joint arthroplasty in orthotopic liver transplant recipients. J Arthroplasty 1996;11(8):889.
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10. Klatt BA, Steele GD, Fedorka CJ, et al. Solid organ transplant patients experience high rates of infection and other complications after total knee arthroplasty. J Arthroplasty 2013;28(6):960. 11. Ferguson RM, Henry ML, Elkhammas EA, et al. Twenty years of renal transplantation at Ohio State University: the results of five eras of immunosuppression. Am J Surg 2003;186(3):306. 12. Durrbach A, Francois H, Beaudreuil S, et al. Advances in immunosuppression for renal transplantation. Nat Rev Nephrol 2010;6(3):160. 13. McDonald-Hyman C, Turka LA, Blazar BR. Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Sci Transl Med 2015;7(280):280rv2. 14. Wong JM, Khan WS, Chimutengwende-Gordon M, et al. Recent advances in designs, approaches and materials in total knee replacement: literature review and evidence today. J Perioper Pract 2011;21(5):165. 15. Morris PJ. Transplantationda medical miracle of the 20th century. N Engl J Med 2004;351(26):2678. 16. Sayegh MH, Carpenter CB. Transplantation 50 years laterdprogress, challenges, and promises. N Engl J Med 2004;351(26):2761. 17. Meier-Kriesche HU, Baliga R, Kaplan B. Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation 2003;75(8):1291. 18. Yu TM, Lin CL, Chang SN, et al. Osteoporosis and fractures after solid organ transplantation: a nationwide population-based cohort study. Mayo Clinic Proc 2014;89(7):888. 19. Bia M. Evaluation and management of bone disease and fractures post transplant. Transplant Rev (Orlando) 2008;22(1):52. 20. Epstein S. Post-transplantation bone disease: the role of immunosuppressive agents and the skeleton. J Bone Miner Res 1996;11(1):1. 21. Dolgos S, Hartmann A, Isaksen GA, et al. Osteoporosis is a prevalent finding in patients with solid organ failure awaiting transplantationda population based study. Clin Transpl 2010;24(5):E145. 22. Shaikh KA, Helbig GM, Shapiro SA, et al. Spinal surgery following organ transplantation. J Neurosurg Spine 2011;14(6):779. 23. Gallagher KA, Ravin RA, Schweitzer E, et al. Outcomes and timing of aortic surgery in renal transplant patients. Ann Vasc Surg 2011;25(4):448. 24. Wei CK, Chang CM, Lee CH, et al. Acute appendicitis in organ transplantation patients: a report of two cases and a literature review. Ann Transplant 2014;19: 248. 25. Koonce SL, Giles B, McLaughlin SA, et al. Breast reconstruction after solid organ transplant. Ann Plast Surg 2015;75:343e7. 26. Elixhauser A, Steiner C, Harris DR, et al. Comorbidity measures for use with administrative data. Med Care 1998;36(1):8. 27. Chu YT, Ng YY, Wu SC. Comparison of different comorbidity measures for use with administrative data in predicting short- and long-term mortality. BMC Health Serv Res 2010;10:140. 28. Shin JH, Worni M, Castleberry AW, et al. The application of comorbidity indices to predict early postoperative outcomes after laparoscopic Roux-en-Y gastric bypass: a nationwide comparative analysis of over 70,000 cases. Obes Surg 2013;23(5):638. 29. Saez-Gimenez B, Berastegui C, Loor K, et al. Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando) 2015;29(2):85. 30. Anderson Jr FA, Huang W, Friedman RJ, et al. Prevention of venous thromboembolism after hip or knee arthroplasty: findings from a 2008 survey of US orthopedic surgeons. J Arthroplasty 2012;27(5):659. 31. Issa N, Kukla A, Ibrahim HN. Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence. Am J Nephrol 2013;37(6):602. 32. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4(2):481. 33. Cavanaugh PK, Chen AF, Rasouli MR, et al. Total joint arthroplasty in transplant recipients: in-hospital adverse outcomes. J Arthroplasty 2015;30(5):840. 34. Leung KH, Chiu KY, Yan CH, et al. Review article: venous thromboembolism after total joint replacement. J Orthop Surg (Hong Kong) 2013;21(3):351. 35. Zhu Y, Zhang F, Chen W, et al. Risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and meta-analysis. J Hospital Infection 2015;89(2):82.
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Appendix 1 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes for Elixhauser Comorbidities. Elixhauser Comorbidity
ICD-9-CM Diagnosis Code
Congestive heart failure Valvular disease Pulmonary circulation disorders
398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.0-428.9 093.20-093.24, 394.0-397.1, 397.9, 424.0-424.99, 746.3-746.6, V42.2, V43.3 415.11-415.19, 416.0-416.9, 417.9 440-440.9, 441.00-441.9, 442.0-442.9, 443.1-443.9, 444.21-444.22, 447.1, 449 557.1, 557.9, V43.4 401.1, 401.9, 642.00-642.04, 401.0, 402.00-405.99, 437.2, 642.10-642.24 642.70-642.94 342.0-344.9, 438.20-438.53, 780.72, 780.72 330.1-331.9, 332.0, 333.4, 333.5, 333.71, 333.72, 333.79, 333.85, 333.94 334.0-335.9, 338.0, 340, 341.1-341.9, 780.3, 780.33, 780.39, 780.97, 784.3, 780.31, 780.32, 345.00-345.11, 345.2-345.3, 345.40-345.91, 347.00-347.01 347.10-347.11, 649.40-649.44, 768.7, 768.70, 768.71, 768.72 490-492.8, 493.00-493.92, 494-494.1, 495.0-505, 506.4 249.00-249.31, 250.00-250.33, 648.00-648.04, 249.00-249.31 249.40-249.91, 250.40-250.93, 775, 249.40-249.91 243-244.2, 244.8, 244.9 403.01, 403.11, 403.90, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92 404.93, 585.3, 585.4, 585.5, 585.6, 585.9, 586, V56.0-V56.32, V56.8V42.0 V45.1, V45.11, V45.12, V45.11, V45.12 070.22, 070.23, 070.32, 070.33, 070.44, 070.54, 456.0, 456.1, 456.20, 456.21 571.0, 571.2, 571.3, 571.40-571.49, 571.5, 571.6, 571.8, 571.9, 572.3, 572.8 573.5, V42.7 531.41, 531.51, 531.61, 531.70, 531.71, 531.91, 532.41, 532.51, 532.61 532.70, 532.71, 532.91, 533.41, 533.51, 533.61, 533.70, 533.71, 533.91 534.41, 534.51, 534.61, 534.70, 534.71, 534.91 042-044.9 200.00-202.38, 202.50-203.01, 203.02-203.82, 203.8-203.81, 238.6, 273 203.02, 203.82 196.0-199.1, 209.70, 209.71, 209.72, 209.73, 209.74, 209.75, 209.79, 789.51 209.70, 209.71, 209.72, 209.73, 209.74, 209.75, 209.79 140.0-172.9, 174.0-175.9, 179-195.8, 209.00-209.24, 209.25-209.3, 209.30209.36, 258.01-258.03, 209.00-209.24, 209.25-209.3, 209.31-209.36 701.0, 710.0-710.9, 714.0-714.9, 720.0-720.9, 725 286.0-286.9, 287.1, 287.3-287.5, 289.84, 649.30-649.34, 289.84, 286.52 286.53, 286.59 278.0, 278.00, 278.01, 278.03, 649.10-649.14, 793.91, V85.30-V85.39, V85.41V85.45, V85.54, 278.03, V85.41-V85.45 260-263.9, 783.21, 783.22 276.0-276.9 280.0, 648.20-648.24 280.1-281.9, 285.21-285.29, 285.9 291.0-291.3, 291.5, 291.8, 291.81, 291.82, 291.89, 291.9, 303.00-303.93 305.00-305.03 292.0, 292.82-292.89, 292.9, 304.00-304.93, 305.20-305.93, 648.30-648.34 295.00-298.9, 299.10, 299.11 300.4, 301.12, 309.00, 309.1, 311
Peripheral vascular disease Hypertension Paralysis
Other neurologic disorders Chronic pulmonary disease Diabetes without chronic complications Diabetes with chronic complications Hypothyroidism
Renal failure
Liver disease
Chronic peptic ulcer disease HIV and AIDS Lymphoma Metastatic cancer Solid tumor without metastasis Rheumatoid arthritis/collagen vascular diseases Coagulation deficiency Obesity Weight loss Fluid and electrolyte disorders Blood loss anemia Deficiency anemia Alcohol abuse Drug abuse Psychoses Depression
HIV, human immunodeficiency virus; AIDS, acquired immune deficiency syndrome.
Contents lists available at ScienceDirect
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Original article
How Do Previous Solid Organ Transplant Recipients Fare After Primary Total Knee Arthroplasty? Mitchell R. Klement, MD *, Colin T. Penrose, BA, BS, Abiram Bala, BA, Samuel S. Wellman, MD, Michael P. Bolognesi, MD, Thorsten M. Seyler, MD, PhD Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 August 2015 Received in revised form 26 September 2015 Accepted 2 October 2015 Available online XXX
Introduction: Total knee arthroplasty (TKA) has been proven to increase knee outcome scores after solid organ transplantation (SOT), but many authors are concerned about a higher complication rate. The purpose of this study is to evaluate the complication profile of TKA after previous SOT. Methods: A search of the entire Medicare database from 2005 to 2011 was performed using International Classification of Disease, version 9, codes to identify 3339 patients who underwent TKA after 1 or more solid organ transplants including the kidney (2321), liver (772), lung (129), heart (412), and pancreas (167). A cohort of 1,685,295 patients served as a control with minimum 2-year follow-up. Postoperative complications at 30-day, 90-day, and overall time points were compared between the 2 cohorts. Results: Patients with any SOT were younger (age: <65, odds ratio [OR]: 6.58, P < .001), male (OR: 1.88, P < .001), and medically complex (significant increase in 28 of 29 Elixhauser comorbidities, P < .05). There was a significant increase (P < .05) in 11 of 13 (84.6%) recorded postoperative medical complications rates at 90 days. There was a significant increase overall in periprosthetic infection (OR: 2.11, P < .001), periprosthetic fracture (OR: 1.78, P < .001), and TKA revision (OR: 1.36, P < .001). When analyzed by individual organ, heart and lung transplants carried the fewest medical and surgical complications. Conclusion: The results of this study demonstrate that patients with previous SOT who undergo elective primary TKA have more postoperative complications in the global period and at short-term follow-up. Yet, complication profiles by individual organ varied significantly. © 2015 Elsevier Inc. All rights reserved.
Keywords: primary knee arthroplasty total knee replacement solid organ transplant complications transplantation
Since 2003 at least 25,000 solid organ transplants (SOTs) have been performed annually in the United States, with 27,036 completed in 2014. While this number has reached a plateau because of organ availability, evolutions in procurement, implantation technique, and posttransplant immunosuppression have dramatically increased recipient survivorship. The majority of organ transplants were in patients aged >50 years, and with the exception of lung and intestine transplantation, 5-year survival rates for this age group average 70% [1]. Small retrospective cohort studies have
Investigation was performed at the Duke University Medical Center, Durham, NC. No funding was provided for this study. One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2015.10.007. * Reprint requests: Mitchell R. Klement, MD, Duke University Medical Center, Department of Orthopaedic Surgery, Box 3000, Durham, NC 27710. http://dx.doi.org/10.1016/j.arth.2015.10.007 0883-5403/© 2015 Elsevier Inc. All rights reserved.
shown that total knee arthroplasty (TKA) in patients with a prior SOT is a worthwhile endeavor as the rate patient reported good/ excellent outcomes after kidney, liver, and lung transplantation ranges from 92% to 100% [2]. In addition, Knee Society scores in these patients were significantly increased after TKA compared to preoperative values (Knee Society score, kidney: 51.2-89.2, liver: 55.0-93.8, and lung: 58.2-92; all P < .05) [2]. Promising results have also been shown in prior cardiac and lung transplant recipients with 100% good/excellent patient-reported outcomes in lung patients at final follow-up [3,4]. However, given the need for continued immunosuppression and increased medical comorbidities, many authors have cited concerns regarding increased infection and other postoperative complications in this patient population [5-7]. As perioperative and postoperative complications will be linked to surgeon and hospital reimbursement, little is known about complication profiles in this patient population in the global period (first 90-days after surgery) and at short-term follow-up. Furthermore earlier reports of TKA in SOT patients focused on the treatment of steroid-induced osteonecrosis [8], while the majority of transplant patients undergoing TKA today are for
2
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
treatment of end-stage osteoarthritis[8,9]. Many of the studies reporting outcomes in total joint arthroplasty and solid organ transplantation to date have been limited by a small number of patients [3,8,9]. A majority of the literature has also focused on TKA in kidney and liver transplantation, but kidney transplants have been decreasing for the past 3 years, whereas lung and heart transplants are on the rise [1]. In addition, to achieve adequate numbers, collection for these studies often spans decades, during which significant advances in the fields of transplant and arthroplasty have occurred [10-14] The purpose of this study was to use a large national database to identify patients undergoing TKA after various SOTs with a specific focus on postoperative complications. A large national database study would also enable comparison between individual organ transplant types to control to see if one fares worse than the others. We hypothesize that SOT recipients in general will have an increased postoperative complication profile compared to controls, and the individual organ complication profiles will vary. Methods A retrospective review of a Medicare database was conducted from 2005 to 2011 containing 100% of inpatient and 100% of outpatient administrative records using Pearl Diver technologies (Warsaw, IN). This study was exempt from institutional review board approval at our institution as deidentified patient data were reviewed. All patients who underwent TKA were included and identified using both the corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code 81.54 and Current Procedural Terminology codes 27445, 27446, and 27447. By looking at distinct patient volumes, patients with bilateral TKA and total hip arthroplasty were excluded. Using the Pearl Diver Boolean command language, the ICD-9 diagnosis code for the relevant SOTs (Kidney V42.0, Heart V42.1, Lung V42.6, Liver V42.7, Pancreas V42.83) was used to identify the cohort of patients who carried these diagnoses before the date of their primary TKA. The control group was defined as patients who did not carry a diagnosis of these SOTs before their primary TKA. Using relevant ICD-9-CM and Current Procedural Terminology codes, the rates of various postoperative complications that occurred within 30 days, within 90 days, and overall were evaluated. Minimum 2-year follow-up was required for inclusion. Comorbidities of the various groups were identified based on the Elixhauser comorbidity index and relevant ICD-9 diagnosis codes (Appendix 1). Standard bivariate descriptive statistics were performed to compare both the comorbidity and complication rates. A chi-squared test was used to compare categorical variables, and a 2-sided Fisher exact test was used for categorical variables with decreased incidence (<0.01%). P < .05 indicated statistical significance.
younger age versus the control cohort (age: <65, OR: 6.58, 95% CI: 6.15-7.06, P < .001, Table 1). Patient Comorbidities Not surprisingly, the transplant cohort as a whole represented a medically more complex population with a statistically significant increase (P < .05) in 28 of 29 Elixhauser medical comorbidities. Notable medical comorbidities more prevalent in this group not related to transplantable end-organ failure included peripheral vascular disease (P ¼ .001), rheumatoid arthritis (P ¼ .001), lymphoma (P ¼ .001), and metastatic cancer (P ¼ .001). Conditions related to transplantable organ failure were also increased such as diabetes (P ¼ .001), chronic obstructive pulmonary disease (P ¼ .001), congestive heart failure (P ¼ .001), and renal failure (P ¼ .001). Furthermore, these complications were also significant across all individual transplant groups. In addition, the transplant cohort overall was more likely to smoke, abuse alcohol, abuse drugs, and carry psychiatric diagnosis of depression (all P < .001). The only medical comorbidity that was not significant was prevalence of peptic ulcer disease (P ¼ .592). Postoperative Medical Complications The transplant cohort overall had a statistically significant increase (P < .05) of 11 of the 13 (84.6%) recorded postoperative medical complications at both the 30- and 90-day time points compared to controls with the exception of stroke. The incidence of pulmonary embolism (PE) was statistically decreased overall in the SOT cohort compared to controls (OR: 0.69, 95% CI: 0.49-0.98, P ¼ .041, Fig. 1). When separated into individual organ at the 30-day time point, lung and heart transplants appeared to have the most favorable complication profile after TKA as only 6 of 13 medical complications were statistically increased, followed by pancreas (7 of 13), liver (7 of 13), and kidney (8 of 13, P < .05, Fig. 1). With regard to 90-day time point, pancreas transplant was the safest with 6 of 15 medical complications being significantly increased, followed by lung (7 of 13), liver (8 of 13), heart (9 of 13), and kidney (10 of 13, Table 2). Acute renal failure (ARF) was the only complication that remained significant (P < .05) across each individual organ at 30 and 90 days postoperatively (Fig. 1, Table 2). Postoperative Surgical Complications The transplant cohort overall had a statistically significant increase (P < .05) of 6 of the 10 recorded acute postoperative surgical Table 1 Patient Demographics.
Results
Control
Patient Demographics From 2005 to 2011 1,685,295 Medicare patients underwent TKA without a prior sold organ transplant. In the same time period, a total of 3334 patients who had prior surgical organ transplant underwent primary TKA. There were 2321 kidney transplants, 772 liver transplants, 129 lung transplants, 412 heart transplants, and 167 pancreas transplants patients. The average duration of followup for the control cohort was 4.02 years, and the average follow-up for the combined SOT cohort was 3.52 years. There were a higher percentage of males undergoing TKA with an SOT than in the control group (50.1% vs 34.8%, odds ratio [OR]: 1.88, 95% CI: 1.752.01, P < .001). In addition, transplant patients underwent TKA at a
Gender Female Male Unknown Age (y) <65 65-69 70-74 75-79 80-84 85 Unknown Total cohort size
Prior SOT
N
%
N
%
1,074,440 587,958 33,832
63.75 34.89 2.01
1629 1673 51
48.86 50.18 1.53
164,055 457,278 431,912 367,631 220,725 84,502 33,832 1,685,295
9.73 27.13 25.63 21.81 13.10 5.01 2.01
1385 799 623 386 130 42 51 3334
41.54 23.97 18.69 11.58 3.90 1.26 1.53
SOT, solid organ transplantation.
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
3
Fig. 1. Forest plot comparing medical complications at 30 days between the combined solid organ transplant cohort and the control. Blue lines indicate that the complication is significantly reduced in the combined solid organ transplant (SOT) cohort, black lines indicate no statistical difference, and red lines indicate that the complication is statistically increased in the combined SOT cohort. DVT, deep venous thrombosis; MI, myocardial infarction; OR, odds ratio; PE, pulmonary embolus; PNA, pneumonia; SIRS, systemic inflammatory response syndrome.
complications at 30-day time point compared to controls including bleeding complications (OR: 1.89, 95% CI: 1.55-2.32, P < .001), wound complications (OR: 2.31, 95% CI: 1.76-3.02, P < .001), cellulitis/seroma (OR: 1.71, 95% CI: 1.47-2.00, P < .001), periprosthetic joint infection (PJI; OR: 2.07, 95% CI: 1.53-2.68, P < .001), and need for irrigation and debridement (OR: 1.83, 95% CI: 1.442.32, P < .001). When analyzed by individual organ at 30 days postoperatively, heart had the fewest complications (2 of 10) followed by lung (3 of 10), pancreas (5 of 10), kidney (5 of 10), and liver (7 of 10). The most striking result was the significant risk of periprosthetic fracture in the heart (OR: 35.66, 95% CI: 14.57-87.30, P < .001) and lung (OR: 35.65, 95% CI: 11.36-85.64, P < .001) cohorts. In addition, only heart had no increased risk of periprosthetic infection (P ¼ .242). At 90 days postoperatively, heart transplant patients had the fewest surgical complications (2 of 7), followed by kidney (3 of 7), pancreas (4 of 7), lung (5 of 7), and liver (5 of 7) with the periprosthetic fracture risk still drastically higher in heart (OR: 8.87, 95% CI; 2.86-20.95, P < .001) and lung (OR: 29.18, 95% CI: 9.3070.05, P < .001) recipients (Table 3). At final follow-up (overall time point), the combined SOT cohort had significantly increase in 5 of 6 recorded surgical complications including PJI (OR: 2.11, 95% CI: 1.82-2.49, P < .001), periprosthetic fracture (OR: 1.78, 95% CI; 1.352.35, P < .001), need for revision (OR; 1.36, 95% CI; 1.14-1.62, P ¼ .001), need for irrigation and debridement (OR; 2.07, 95% CI: 1.772.41, P < .001), and extensor mechanism rupture (OR: 1.69, 95% CI: 1.16-2.46, P ¼ .005). Only patellar complications were not significantly increased (P ¼ .92, Fig. 2). Individually, lung and heart
transplant had an increase in 2 of 6 complications, followed by pancreas (3 of 6), kidney (4 of 6), and lung (4 of 6, Table 4). Discussion Since the first kidney transplant in Boston, 1954, solid organ transplantation has been called a miracle of the 20th century [15]. The recognition of acute rejection and the development of immunosuppressive medications have significantly increased organ survival; however, lifelong immunosuppression carries a dangerous side effect profile [16]. In the first year after kidney transplantation, 11.7% will die from infection, another 10.1% from new malignant neoplasms, and 30.1% from cardiovascular disease as a result [17]. Another complication of immunosuppression unique to orthopedics is the risk of bone disease and osteoporosis. A recent review of Taiwan’s National Health database found a significant increase in osteoporosis (hazard ratio [HR]: 5.14, CI: 3.13-8.43) and osteoporosis-related fractures (HR: 5.76, 95% CI: 3.80-8.74) compared to controls. When analyzed by individual SOT, they found the highest incidence of osteoporosis in the lung transplant cohort (HR: 191.4), followed by heart (HR: 8.40), liver (HR: 9.68), and kidney (HR: 3.40) transplant recipients [18]. While the diagnosis of osteoporosis and fragility fractures was not evaluated the study herein, the authors did find a statistically significant increase in the periprosthetic fracture rate (OR: 1.78, P < .001) overall without an increase in patellar complications. This complication was particularly prominent in heart and lung transplant patients,
4
Table 2 Medical Complications at 90 Days by Individual Organ. 90-Day Complication (Medical)
Control All SOT IN (%)
CI
Liver
P Value IN (%) OR
CI
P Value IN (%)
2.310 1.38 1.10-1.73 .005 10.410 1.92 1.71-2.14 <.001 9.120 1.21 1.07-1.36 .001
2.240 1.34 1.01-1.76 .037 10.340 1.9 1.66-2.17 <.001 8.400 1.1 0.95-1.28 .168
17.520 1.15 1.05-1.26
17.230 1.13 1.01-1.26
.001
2.010 2.47 1.94-3.15 <.001 5.160 0.960 0.930 4.620 2.880 15.060
1.61 0.69 1.20 2.27 3.97 5.52
1.38-1.88 0.49-0.98 0.84-1.71 1.93-2.67 3.24-4.87 4.99-6.10
<.001 .041 1.23 <.001 <.001 <.001
Lung OR
CI
Heart
P Value IN (%) OR
CI
2.720 6.350 7.900
1.63 1.05-2.52 1.12 0.83-1.49 1.03 0.79-1.34
.025 .442 .784
0.001 2.35 0.75-5.65 0.001 0.66 0.21-1.59 13.180 1.83 1.10-3.05
.068 .068 .018
.023
13.990
0.88 0.72-1.08
.24
22.480 0.21 0.09-1.66
<.001
1.810 2.22 1.64-3.02 <.001
1.680
2.06 1.19-3.58
.008
5.040 0.820 0.950 4.520 2.890 15.550
1.57 0.59 1.22 2.22 3.98 6.03
1.31-1.90 0.37-0.93 0.80-1.86 1.82-2.70 3.12-5.08 5.39-6.78
<.001 .022 .341 <.001 <.001 <.001
5.050% 0.001 0.001 4.020 3.240 13.470
1.58 0.46 0.83 1.96 4.48 5.1
1.14-2.18 1.52-1.09 0.27-1.95 1.36-2.81 3.01-6.68 4.15-6.27
.005 .88 1.00 <.001 <.001 <.001
0.001 4.87 1.55-11.67 0.001 0.001 0.001 8.530 0.001 13.180
1.19 2.89 5.16 4.37 5.4 4.97
Pancreas
P Value IN (%) OR
.004
0.38-2.87 .616 0.92-6.94 .033 1.64-12.38 .003 2.35-8.11 <.001 1.72-12.96 .003 2.98-8.28 <.001
CI
3.160 1.9 1.09-3.30 17.480 3.5 2.71-4.51 12.140 1.67 1.24-2.24 19.900 1.35 1.06-1.722 2.670 3.31 1.82-6.03 5.340 0.001 0.001 6.800 3.160 19.660
1.67 0.88 1.57 3.41 4.37 8.02
1.09-2.57 0.28-2.07 0.50-3.70 2.32-5.01 2.51-7.59 6.29-10.23
P Value IN (%) OR
CI
P Value
.02 <.001 .001
0.001 1.8 0.57-4.29 8.980 1.63 0.96-2.77 7.780 1.02 0.57-1.78
.211 .068 .944
.014
12.570 0.78 0.49-1.23
.293
<.001
0.001 3.72 1.19-8.88
.013
.017 1.00 .258 <.001 <.001 <.001
6.590 0.001 0.100 0.001 0.001 7.780
2.09 2.21 3.95 1.44 4.14 2.76
1.13-3.86 .015 0.71-5.28 .081 1.26-9.52 .01 0.46-3.44 .406 1.32-9.86 .008 1.57-4.87 <.001
28.850 1.22 1.13-1.32 <.001
28.440 1.2
1.10-1.32 <.001
30.700
1.34 1.15-1.57 <.001
27.130 1.13 0.76-1.66
.53
28.160 1.19 0.96-1.47
.109
31.140 1.37 0.99-1.90
.056
30.680 1.42 1.32-1.53 <.001
30.720 1.43 1.31-1.57 <.001
31.990
1.52 1.31-1.77 <.001
29.460 1.35 0.92-1.97
.116
26.940 1.19 0.96-1.48
.108
31.140 1.46 1.05-2.03
.021
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; MI, myocardial infarction; Afib, atrial fibrillation; DVT, deep venous thrombosis; OR, odds ratio; PE, pulmonary embolus; PNA, pneumonia; SIRS, systemic inflammatory response syndrome.
Table 3 Surgical Complications at 90 Days by Individual Organ. 90-Day Complication (Surgical)
Control All SOT
Kidney
IN (%)
IN (%) OR
CI
MUA Periprosthetic infection Periprosthetic fracture TKA revision Arthrotomy/I&D Patellar complications Extensor mechanism rupture
1.020 0.960
0.720 0.70 2.340 2.48
0.47-1.05 .089 1.98-3.11 <.001
0.600 0.592 0.35-1.00 .048 2.630 2.79 2.17-3.61 <.001
0.001 0.63 0.20-1.49 2.460 2.61 2.65-4.12
0.140
0.001 1.08
0.35-2.84
.812
0.001 1.56
0.50-3.65
0.001 4.71 1.52-11.07
.005
0.001 29.18 9.30-70.05 <.001
0.450 1.250 0.190
0.720 1.6 2.400 1.93 0.001 0.80
1.07-2.39 .021 1.55-2.41 <.001 0.26-1.87 .84
0.730 1.62 2.630 2.12 0.001 1.15
1.01-2.62 .043 1.64-2.74 <.001 0.37-2.69 .63
0.001 1.44 0.46-3.37 2.200 1.77 1.09-2.86 0.001 3.47 1.12-8.16
.408 .018 .016
0.001 0.001 0.000
0.180
0.001 0.813 0.26-1.90
0.001 1.16
0.37-2.73
0.001 3.52 1.14-8.27
.015
P Value IN (%) OR
.839
Liver CI
P Value IN (%) OR
.26
.625
Lung CI
Heart
P Value IN (%) OR .468 <.001
0.000 0.001
CI
0.00 0.00-2.29 4.18 1.33-10.02
P Value IN (%) OR .645 .008
Pancreas CI
0.001 1.19 0.38-2.81 0.001 1.27 0.41-2.99
P Value IN (%) OR .618 .605
CI
0.001 3.00 0.96-7.16 0.001 3.20 1.02-7.62
P Value .029 .023
0.001 8.89 2.86-20.95 <.001
0.000 0.00 0.00-13.11 1.00
8.9 2.14-28.35 <.001 3.17 1.01-7.61 .024 0.00 0.00-12.54 1.00
0.001 2.71 0.87-6.38 0.001 0.96 0.31-2.27 0.000 0.00 0.00-3.89
.04 1.00 1.00
0.001 6.81 2.18-16.24 .001 0.001 2.43 0.77-5.78 .06 0.000 0.00 0.00-9.66 1.00
0.001 21.82 6.95-52.36 <.001
0.000 0.00 0.00-3.95
1.00
0.000 0.00 0.00-9.80
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; MUA, manipulation under anesthesia; OR, odds ratio; TKA, total knee arthroplasty; I&D, irrigation and debridement.
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M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
MI 1.680 Heart failure 5.710 Arrhythmia 7.640 without Afib Arrhythmia 15.52 with Afib Respiratory 0.820 failure DVT 3.250 PE 1.370 Stroke 0.770 PNA 2.090 Sepsis/SIRS 0.740 Acute renal 2.960 failure Postoperative 24.750 anemia Blood 23.580 transfusion
Kidney
IN (%) OR
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
5
Fig. 2. Forest plot comparing surgical complications at overall time point between the combined solid organ transplant cohort and the control. Black lines indicate no statistical difference compared to the control cohort and red lines indicate that the complication is statistically increased in the combined SOT cohort. I&D, irrigation and debridement; TKA, total knee arthroplasty.
correlating with the higher osteoporosis rates found in the Taiwan National database. All SOTs at our institution receive tacrolimus (adjusted to levels) and mycophenolate for the life of the graft if no complications, rejections, or cancers occur. However, heart and lung transplants receive additional steroid at the time of transplantation (methylprednisolone, with additional dose for double lung transplant) and basiliximab, an antibody to the IL-2 receptor of T cells. While the effect of these medications on bone metabolism is conflicting [19,20], patients with chronic lung and heart disease are at increased risk because of physical inactivity, chronic medications, poor nutrition, and smoking status [21]. In addition, among patients awaiting SOT, end-stage lung failure patients had the poorest pretransplant bone mineral density when measured on X-ray absorptiometry compared to liver, kidney, and heart [21]. Furthermore, immunosuppressive medications likely account for the significant increase in wound complications, cellulitis and seroma, and PJI. A similar infection rate was reported by Shaikh [22] in which 1 of 12 patients (8.33%) undergoing spinal surgery after SOT developed an infection. However, general, vascular, and plastic surgeries have reported few to no infectious complications in this patient population undergoing subsequent procedures [23-25]. In addition to being chronically immunosuppressed, the combined SOT cohort represents a medically complex group with significantly increased comorbidities at baseline using the Elixhauser Comorbidity Index. This index has been proven to be a superior measure of patient discrimination for multiple diseases in North America [26,27] and has also been proven to more accurately predict short-term outcomes after operations in general surgery
patients [28]. It should not be surprising then that a more medically complex cohort also had a statistically significant increase in every postoperative medical complication with the exception of stroke and PE (which were significantly decreased). The overall incidence of PE in the control cohort was 1.37% compared to 0.96% in the transplant cohort. However, when analyzed by individual organ, only kidney had a decreased incidence of PE (OR: 0.59, 95% CI: 0.370.93, P ¼ .22), whereas the other organs were not statistically significant (P > .05) and lung was significantly increased (OR: 2.89, 95% CI: 0.92-6.94, P ¼ .033). Patients with solid organ transplantation are considered to be at high risk for venous thromboembolism events as corticosteroids diminish fibrinolysis and calcineurin inhibitors are thought to be prothrombotic [29]. The most common venous thromboembolism prophylactic agent after total joint arthroplasty, enoxaparin, is excreted by the kidneys and the diminished reserve of the transplanted organ, and high incidence of acute renal injury in these patients after total joint arthroplasty may elevate the therapeutic levels of this agent resulting in fewer PEs [30]. Despite type of organ transplanted, acute kidney injury appeared to be the most common postoperative medical complication as this was statistically significant at all time points, consistent with prior study by Ledford et al [2] who saw 25%-50% complication rate in 21 TKAs, with most common complication being ARF. “Calcineurin inhibitor nephrotoxicity” is a welldescribed complication of this type of immunosuppressive agent and likely accounts for the increased risk of acute kidney injury seen overall and in each individual organ transplant in the present study [31,32]. A recent search of the Nationwide Inpatient Sample
1.00 0.000 0.00 0.00-3.62 .057 0.001 2.45 0.79-5.78
SOT, solid organ transplant; IN, incidence; OR, odds ratio; CI, 95% confidence interval; TKA, total knee arthroplasty; I&D, irrigation and debridement.
.001 0.001 8.06 2.57-19.08 .443 0.42-3.05 0.001 1.3 .057 0.780 1.56 0.98-2.48 .005 0.840 1.69 1.16-2.46 0.64
0.001 1.03 0.33-2.46 .817 8.980 3.78 2.22-6.42 <.001 0.001 4.97 1.59-11.86 .004 .038 .157 .192 4.610 1.62 1.02-2.56 3.640 1.44 0.86-2.42 0.000 0.00 0.00-1.17 .428 .286 1.00 0.001 1.35 0.43-3.24 0.001 1.45 0.49-3.70 0.000 0.00 0.00-3.78 3.710 1.29 1.04-1.60 .02 5.600 2.27 1.90-2.71 <.001 43.560 1.11 0.68-1.83 .653 3.900 1.36 1.14-1.62 .001 5.130 2.07 1.77-2.41 <.001 44.660 1.02 0.66-1.57 .92 2.90 2.54 0.62
4.400 1.54 1.09-2.17 .013 4.920 1.98 1.43-2.74 <.001 0.001 1.05 0.34-2.46 .816
.015 0.001 3.55 1.13-8.46 .413 0.001 1.41 0.45-3.32 .005 0.001 4.64 1.48-11.13 .007 1.380 1.61 1.13-2.28 1.530 1.78 1.35-2.36 <.001 0.86
2.070 2.43 1.48-3.99 <.001
0.001 1.12 0.36-2.68 5.580 2.15 1.41-3.28 <.001 .401 0.001 1.47 0.46-3.52 5.960 2.31 1.71-3.11 <.001 5.820 2.25 1.89-2.68 <.001 5.490 2.11 1.82-2.49 <.001 2.67
Periprosthetic Infection Periprosthetic fracture TKA revision Arthrotomy/I&D Patellar complications Extensor mechanism rupture
CI P Value IN (%) OR IN (%)
IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
P Value IN (%) OR
CI
Pancreas Heart Lung Liver Kidney Control All SOT
Overall Complication (Surgical)
Table 4 Surgical Complications at Overall Time Point by Individual Organ.
.807
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
P Value
6
database was performed by Cavanaugh et al [33] showed similar results. They identified patients with history of transplant and joint arthroplasty (primary or revision) from 1993 to 2011, with a specific focus on in-hospital complications. They found kidney transplant increased risk of systemic infection (OR: 2.85), deep venous thrombosis (OR: 2.07), ARF (OR: 3.48), and respiratory (OR: 1.34) and cardiac (OR: 1.21) complications. Liver transplant was associated with respiratory complications (OR: 1.68), cardiac complications (OR: 1.34), and ARF (OR: 4.48). Other transplants grouped together (including lung, bone marrow, and pancreas) were associated with wound complications (OR: 2.13), respiratory complications (OR: 2.06), and ARF (OR: 4.42). Similar results were seen in the present study but extended out to the 30- and 90-day time points. This may be worrisome as patients may still be at increased risk of medical complications after discharge. Furthermore, complications such as DVT and PE typically occur 20-30 days postoperatively and may not be adequately captured but examining only in-house complication profiles [34]. In addition, the rate of postoperative complications in the present study varied drastically compared to previously published data. Blood transfusion rates in our study were 30% in the postoperative period after SOT compared to 80% rate of transfusion reported previously after TKA in SOT patients [2]. Accurate reporting of this complication is particularly important, as blood transfusions have been individually associated with increased PJI [35]. PE was previously reported to be 1.7% after SOT and was 0.9% in our study [5]. Angermeier et al [5] reported a periprosthetic infection rate of 22% in 9 TKA patients, compared to 5.3% overall in our series, with no increased risk in lung and pancreas transplants. Their overall revision rate was 22% (2 of 9) compared to 3.9% in our series. Finally, Klatt et al [10] previously found no difference when comparing overall complications in renal transplants (11 knees) versus nonrenal transplants (12 knees, P ¼ .147) but did show an increased infection rate in the renal cohort (P ¼ .022). The discrepancies between the existing literature and the present study are likely attributed to a significantly larger sample size and perhaps a more representative patient population. Many of the previous studies are isolated to single, large, tertiary academic centers, whereas the data herein represent a nationwide sample. Strengths of this study include the utilization of a large, Medicare database to achieve an adequate sample size to statistically and accurately report complications rates of TKA after renal, liver, lung, heart, and pancreas transplantation. The nationwide sample provides the ability to compare the SOT group overall, as well as individual organ, to a large control cohort. To the authors’ knowledge, this is the first study to compare comorbidities, medical complications, and surgical complications between individual organ transplants for TKA after SOT. Limitations of a large database study include the potential for confounding variables that are available for analysis, including surgical implant, surgical technique, and type of surgical implant used. Surgical variables unique to transplantation were not available such as the dose and duration of immunosuppression and the nature of the graft (single vs double lung, cadaver versus livingrelated donor). The quality of the data soles relies on accurate coding at the time of patient encounter. This data were gathered from the Medicare database and may not apply to all patients or those from different countries. Pearl Diver technologies enable analysis of complications in the global period (first 90 days after surgery) and at short-term follow-up, data lacking from previous large-database studies investigating this topic. However, the cost of using this technology and the Medicare database standard analytical files is that each standard analytical file form is not available for individual review. Variables such as age, gender, comorbidities, and complications are counted from the coding and cannot be matched.
M.R. Klement et al. / The Journal of Arthroplasty xxx (2015) 1e7
Furthermore, advanced statistics such as multivariate analysis cannot be performed to eliminate confounding variables. Finally, knee outcome scores, postoperative function, and patient satisfaction were not recorded in this database. This study suggests that overall SOT patients undergoing TKA are more likely to be male, younger, and have more medical comorbidities than traditional knee arthroplasty candidates. When combined SOT patients have significantly increased medical and surgical complications after their total knee arthropalsty surgery but at lower rates than traditionally reported, potentially due to increased patient cohorts. However, this study proves that not all individual transplants have a similar complication profiles, and special consideration should be given to renal and liver transplant patients as they are more at risk. The authors recommend a multidisciplinary approach to the care of these patients with early involvement of medical and transplant services. Regional anesthesia, multimodal pain therapy, and an enhanced recovery protocol may be necessary to limit postoperative complications. In addition, heart and lung patients had a lower complication profile than the overall liver, pancreas, and kidney cohorts. Conclusion In conclusion, the extensive reporting of medical and surgical complications after individual organ transplant in the present study will allow arthroplasty surgeons to better council their patients on the risks of knee arthroplasty surgery and ensure proper care perioperatively. This is also a significant reference for complication profiles in the “bundle-of-care” and outcome-based payment era. References 1. Annual Data Report of the US Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). Introduction. Am J Transplant 2013;13(Suppl 1):8. 2. Ledford CK, Watters TS, Wellman SS, et al. Risk versus reward: total joint arthroplasty outcomes after various solid organ transplantations. J Arthroplasty 2014;29(8):1548. 3. Isono SS, Woolson ST, Schurman DJ. Total joint arthroplasty for steroid-induced osteonecrosis in cardiac transplant patients. Clinical Orthop Relat Res 1987;217:201. 4. Ledford CK, Watters TS, Wellman SS, et al. Outcomes of primary total joint arthroplasty after lung transplantation. J Arthroplasty 2014;29(1):11. 5. Angermeier EW, Demos HA, Del Schutte H, et al. Complications of hip and knee joint replacement in solid-organ transplant patients. J Surg Orthop Adv 2013;22(3):204. 6. Vergidis P, Lesnick TG, Kremers WK, et al. Prosthetic joint infection in solid organ transplant recipients: a retrospective case-control study. Transpl Infect Dis 2012;14(4):380. 7. Papagelopoulos PJ, Hay JE, Galanis E, et al. Infection around joint replacements in patients who have a renal or liver transplantation (79-A: 36-43, Jan. 1997), Tannenbaum et al. J Bone Joint Surg Am 1998;80(4):607. 8. Maguire WB, Muscio P, Dodd PA. The results of joint replacement surgery in renal transplant patients. Aust N Z J Surg 1981;51(6):534. 9. Papagelopoulos PJ, Hay JE, Galanis EC, et al. Total joint arthroplasty in orthotopic liver transplant recipients. J Arthroplasty 1996;11(8):889.
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10. Klatt BA, Steele GD, Fedorka CJ, et al. Solid organ transplant patients experience high rates of infection and other complications after total knee arthroplasty. J Arthroplasty 2013;28(6):960. 11. Ferguson RM, Henry ML, Elkhammas EA, et al. Twenty years of renal transplantation at Ohio State University: the results of five eras of immunosuppression. Am J Surg 2003;186(3):306. 12. Durrbach A, Francois H, Beaudreuil S, et al. Advances in immunosuppression for renal transplantation. Nat Rev Nephrol 2010;6(3):160. 13. McDonald-Hyman C, Turka LA, Blazar BR. Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Sci Transl Med 2015;7(280):280rv2. 14. Wong JM, Khan WS, Chimutengwende-Gordon M, et al. Recent advances in designs, approaches and materials in total knee replacement: literature review and evidence today. J Perioper Pract 2011;21(5):165. 15. Morris PJ. Transplantationda medical miracle of the 20th century. N Engl J Med 2004;351(26):2678. 16. Sayegh MH, Carpenter CB. Transplantation 50 years laterdprogress, challenges, and promises. N Engl J Med 2004;351(26):2761. 17. Meier-Kriesche HU, Baliga R, Kaplan B. Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation 2003;75(8):1291. 18. Yu TM, Lin CL, Chang SN, et al. Osteoporosis and fractures after solid organ transplantation: a nationwide population-based cohort study. Mayo Clinic Proc 2014;89(7):888. 19. Bia M. Evaluation and management of bone disease and fractures post transplant. Transplant Rev (Orlando) 2008;22(1):52. 20. Epstein S. Post-transplantation bone disease: the role of immunosuppressive agents and the skeleton. J Bone Miner Res 1996;11(1):1. 21. Dolgos S, Hartmann A, Isaksen GA, et al. Osteoporosis is a prevalent finding in patients with solid organ failure awaiting transplantationda population based study. Clin Transpl 2010;24(5):E145. 22. Shaikh KA, Helbig GM, Shapiro SA, et al. Spinal surgery following organ transplantation. J Neurosurg Spine 2011;14(6):779. 23. Gallagher KA, Ravin RA, Schweitzer E, et al. Outcomes and timing of aortic surgery in renal transplant patients. Ann Vasc Surg 2011;25(4):448. 24. Wei CK, Chang CM, Lee CH, et al. Acute appendicitis in organ transplantation patients: a report of two cases and a literature review. Ann Transplant 2014;19: 248. 25. Koonce SL, Giles B, McLaughlin SA, et al. Breast reconstruction after solid organ transplant. Ann Plast Surg 2015;75:343e7. 26. Elixhauser A, Steiner C, Harris DR, et al. Comorbidity measures for use with administrative data. Med Care 1998;36(1):8. 27. Chu YT, Ng YY, Wu SC. Comparison of different comorbidity measures for use with administrative data in predicting short- and long-term mortality. BMC Health Serv Res 2010;10:140. 28. Shin JH, Worni M, Castleberry AW, et al. The application of comorbidity indices to predict early postoperative outcomes after laparoscopic Roux-en-Y gastric bypass: a nationwide comparative analysis of over 70,000 cases. Obes Surg 2013;23(5):638. 29. Saez-Gimenez B, Berastegui C, Loor K, et al. Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando) 2015;29(2):85. 30. Anderson Jr FA, Huang W, Friedman RJ, et al. Prevention of venous thromboembolism after hip or knee arthroplasty: findings from a 2008 survey of US orthopedic surgeons. J Arthroplasty 2012;27(5):659. 31. Issa N, Kukla A, Ibrahim HN. Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence. Am J Nephrol 2013;37(6):602. 32. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4(2):481. 33. Cavanaugh PK, Chen AF, Rasouli MR, et al. Total joint arthroplasty in transplant recipients: in-hospital adverse outcomes. J Arthroplasty 2015;30(5):840. 34. Leung KH, Chiu KY, Yan CH, et al. Review article: venous thromboembolism after total joint replacement. J Orthop Surg (Hong Kong) 2013;21(3):351. 35. Zhu Y, Zhang F, Chen W, et al. Risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and meta-analysis. J Hospital Infection 2015;89(2):82.
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Appendix 1 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes for Elixhauser Comorbidities. Elixhauser Comorbidity
ICD-9-CM Diagnosis Code
Congestive heart failure Valvular disease Pulmonary circulation disorders
398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.0-428.9 093.20-093.24, 394.0-397.1, 397.9, 424.0-424.99, 746.3-746.6, V42.2, V43.3 415.11-415.19, 416.0-416.9, 417.9 440-440.9, 441.00-441.9, 442.0-442.9, 443.1-443.9, 444.21-444.22, 447.1, 449 557.1, 557.9, V43.4 401.1, 401.9, 642.00-642.04, 401.0, 402.00-405.99, 437.2, 642.10-642.24 642.70-642.94 342.0-344.9, 438.20-438.53, 780.72, 780.72 330.1-331.9, 332.0, 333.4, 333.5, 333.71, 333.72, 333.79, 333.85, 333.94 334.0-335.9, 338.0, 340, 341.1-341.9, 780.3, 780.33, 780.39, 780.97, 784.3, 780.31, 780.32, 345.00-345.11, 345.2-345.3, 345.40-345.91, 347.00-347.01 347.10-347.11, 649.40-649.44, 768.7, 768.70, 768.71, 768.72 490-492.8, 493.00-493.92, 494-494.1, 495.0-505, 506.4 249.00-249.31, 250.00-250.33, 648.00-648.04, 249.00-249.31 249.40-249.91, 250.40-250.93, 775, 249.40-249.91 243-244.2, 244.8, 244.9 403.01, 403.11, 403.90, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92 404.93, 585.3, 585.4, 585.5, 585.6, 585.9, 586, V56.0-V56.32, V56.8V42.0 V45.1, V45.11, V45.12, V45.11, V45.12 070.22, 070.23, 070.32, 070.33, 070.44, 070.54, 456.0, 456.1, 456.20, 456.21 571.0, 571.2, 571.3, 571.40-571.49, 571.5, 571.6, 571.8, 571.9, 572.3, 572.8 573.5, V42.7 531.41, 531.51, 531.61, 531.70, 531.71, 531.91, 532.41, 532.51, 532.61 532.70, 532.71, 532.91, 533.41, 533.51, 533.61, 533.70, 533.71, 533.91 534.41, 534.51, 534.61, 534.70, 534.71, 534.91 042-044.9 200.00-202.38, 202.50-203.01, 203.02-203.82, 203.8-203.81, 238.6, 273 203.02, 203.82 196.0-199.1, 209.70, 209.71, 209.72, 209.73, 209.74, 209.75, 209.79, 789.51 209.70, 209.71, 209.72, 209.73, 209.74, 209.75, 209.79 140.0-172.9, 174.0-175.9, 179-195.8, 209.00-209.24, 209.25-209.3, 209.30209.36, 258.01-258.03, 209.00-209.24, 209.25-209.3, 209.31-209.36 701.0, 710.0-710.9, 714.0-714.9, 720.0-720.9, 725 286.0-286.9, 287.1, 287.3-287.5, 289.84, 649.30-649.34, 289.84, 286.52 286.53, 286.59 278.0, 278.00, 278.01, 278.03, 649.10-649.14, 793.91, V85.30-V85.39, V85.41V85.45, V85.54, 278.03, V85.41-V85.45 260-263.9, 783.21, 783.22 276.0-276.9 280.0, 648.20-648.24 280.1-281.9, 285.21-285.29, 285.9 291.0-291.3, 291.5, 291.8, 291.81, 291.82, 291.89, 291.9, 303.00-303.93 305.00-305.03 292.0, 292.82-292.89, 292.9, 304.00-304.93, 305.20-305.93, 648.30-648.34 295.00-298.9, 299.10, 299.11 300.4, 301.12, 309.00, 309.1, 311
Peripheral vascular disease Hypertension Paralysis
Other neurologic disorders Chronic pulmonary disease Diabetes without chronic complications Diabetes with chronic complications Hypothyroidism
Renal failure
Liver disease
Chronic peptic ulcer disease HIV and AIDS Lymphoma Metastatic cancer Solid tumor without metastasis Rheumatoid arthritis/collagen vascular diseases Coagulation deficiency Obesity Weight loss Fluid and electrolyte disorders Blood loss anemia Deficiency anemia Alcohol abuse Drug abuse Psychoses Depression
HIV, human immunodeficiency virus; AIDS, acquired immune deficiency syndrome.