Outcomes of Primary Total Joint Arthroplasty After Lung Transplantation

The Journal of Arthroplasty 29 (2014) 11–15

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Outcomes of Primary Total Joint Arthroplasty After Lung Transplantation Cameron K. Ledford, MD , Tyler Steven Watters, MD, Samuel S. Wellman, MD, David E. Attarian, MD, Michael P. Bolognesi, MD Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina

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Article history: Received 12 March 2013 Accepted 26 March 2013 Keywords: lung transplantation hip arthroplasty knee arthroplasty immunosuppression

a b s t r a c t Lung transplantation is increasingly common with improving survival rates. Post-transplant patients can be expected to seek total hip (THA) and knee arthroplasty (TKA) to improve their quality of life. Outcomes of 20 primary total joint arthroplasties (15 THA, 5 TKA) in 14 patients with lung transplantation were reviewed. Clinical follow-up time averaged 27.5 and 42.8 months for THA and TKA respectively. Arthroplasty indications included osteonecrosis, osteoarthritis, and fracture. All patients subjectively reported good or excellent outcomes with a final average Harris Hip Score of 88.7, Knee Society objective and functional score of 92.0. There were 4 minor and 1 major acute perioperative complications. 1 late TKA infection was successfully treated with two-stage revision. The mortality rate was 28.5% (4/14 patients) at an average 20.6 months following but unrelated to arthroplasty. Overall, total joint arthroplasty can be safely performed and provide good functional outcomes in lung transplant recipients. © 2014 Elsevier Inc. All rights reserved.

Lung transplantation is increasingly common worldwide. The International Society for Heart and Lung Transplantation recently reported that a total of 3519 lung transplantation procedures were performed in 2010, the highest registry reported number to date [1]. Like recipients of other solid organ transplants, these patients require lifelong treatment with corticosteroids and immunosuppressive agents to prevent and/or treat graft rejection. While necessary and responsible for improved survival, these therapies have distinct side effects that affect the musculoskeletal system. Chronic and high-dose steroid use can lead to osteonecrosis of joints, particularly the femoral head [2], which can lead to debilitating degenerative joint disease. In lung transplant recipients, the incidence of symptomatic osteonecrosis has been reported as 10% [3]. Moreover, pre-existing bone disease and post-transplant hormone-related bone loss in solid organ transplant recipients result in osteoporosis and fractures in up to 20%–40% of patients [4]. As the incidence of lung transplantation increases and survival continues to improve, more of these patients will seek orthopaedic surgeons for musculoskeletal care to address conditions such as degenerative joint disease, which can have a profound effect on their post-transplant quality of life. Concerns regarding the relative safety of elective arthroplasty in the post-transplant population include the potential increased risk of perioperative medical complications, increased risk of infection in the setting of chronic immunosuppres-

The Conflict of Interest statement associated with this article can be found at http:// dx.doi.org/10.1016/j.arth.2013.03.029. Reprint requests: Cameron Ledford, MD, Department of Orthopaedic Surgery, Duke University Medical Center, 200 Trent Drive, Box 3000, Durham, NC 27710. 0883-5403/2901-0003$36.00/0 – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.arth.2013.03.029

sion, and increased risk of fracture or loosening in the setting of osteoporosis and bone loss. Outcomes of total hip arthroplasty (THA) and total knee arthroplasty (TKA) have been reported previously in renal [5–8], cardiac [9–11], and liver transplant cohorts [12,13]. Interestingly, many of these studies have not identified an increased risk of periprosthetic infection, but do acknowledge an increased risk of overall complications in these populations. To the authors’ knowledge, however, no reports have been published on the outcomes of elective total joint arthroplasty in lung transplant recipients. The purpose of this study was to examine the outcome of total hip and knee arthroplasty following lung transplant with specific focus on perioperative complications and infection risk, in addition to functional outcomes.

Materials and Methods This study retrospectively reviewed all patients who underwent primary total joint arthroplasty (TJA) following bilateral orthotopic lung transplantation at Duke University Medical Center between 2006 and 2012. 20 total joint arthroplasties in 14 pulmonary transplant recipients were identified through an internal surgical database search for both the ICD-9 code V42.6 (Lung replaced by transplant) and the Current Procedural Terminology code 27130 (THA) or 27447 (TKA). Patients were excluded if b18 years old, did not have lung transplant prior to arthroplasty, failed or received N1 lung transplant, or received additional or separate solid organ transplant. The Institutional Review Board approved the study prior to investigation. Lung transplantation was performed in patients with respiratory failure for pulmonary fibrosis, chronic obstructive pulmonary disease

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(COPD), and pulmonary hypertension. Each patient presented for elective joint arthroplasty with hip or knee pain that markedly limited function and failed to improve with conservative treatment measures. They underwent extensive pulmonary function testing, indepth anesthesia assessment and primary transplant specialist medical optimization in order to be cleared for surgery. Patients were maintained on immunosuppressant regimen pre-operatively and post-operatively with up to 3 of the following drugs: corticosteroid (Prednisone), tacrolimus, cyclosporine, and/or mycophenolic acid. The most common immunosuppressant regimen was Prednisone and tacrolimus. At the time of surgery, antibiotic prophylaxis with cefazolin was started and continued postoperatively for 24 hours unless there was a penicillin allergy, in which case vancomycin or clindamycin was administered. Extremity preparation within the operative suite included electric clipping of hair, pre-scrub with 2% chlorohexidine and alcohol, followed by sterile application ChloraPrep (San Diego, CA) along with iodine-impregnated sterile drapes. Five separate fellowship-trained academic adult reconstruction surgeons performed the procedures with the majority completed by the senior authors (SSW, DEA, MPB). A variety of approaches for THA were utilized including posterior, direct lateral, and anterolateral. Each TKA was performed through a medial parapatellar approach with use of a tourniquet and all components were posterior-stabilized femoral components with modular tibial trays. Following surgery, all patients except one received the institution’s standard deep vein thrombosis prophylaxis including sequential compression devices, compression stockings, and low-molecular weight heparin (Lovenox) continues for 14 days after discharge. Clinical follow-up was obtained through a retrospective chart review of patient demographics, pre-operative and post-operative multi-disciplinary physician clinical notes (pulmonary transplant, anesthesia, and adult reconstruction), operative reports, discharge summaries, and clinical exams. Specific outcome measures were gathered according to standard clinical intake forms including Harris Hip Scores (HHS), Knee Society Scores (KSS), and Visual Analogue Scale (VAS). Only one patient did not obtain sufficient follow-up to report post-operative outcome measures due to his death from unrelated respiratory failure 10 months after THA. Results Lung Transplant Patients With Total Hip Arthroplasty Fifteen primary THAs were performed in 10 patients with previous lung transplantation (Table 1) including 5 females and 5 males.

Indications for lung transplant were pulmonary fibrosis (5 patients) and COPD (6 patients) with an average age at transplant of 60.7 (47– 70) years old. There was a time interval of 34.8 (4–63) months between lung transplant and hip arthroplasty. Arthroplasty was performed at an average age of 63.5 (52–72) years old for osteonecrosis in 10 hips, osteoarthritis in 4 hips, and fracture in 1 hip. The patients demonstrated similar preoperative comorbidities most commonly some degree of pulmonary compromise (all 10 patients) followed by hypertension (7 patients), chronic kidney disease (7 patients), insulin-dependent diabetes mellitus (4 patients), and coronary artery disease (2 patients). The average body mass index was 26.0 (20.5–34.2) kg/m 2. As described previously, all patients underwent extensive preoperative multi-disciplinary work-up with surgical clearance obtained from primary pulmonary transplant team and anesthesia. All patients received an American Society of Anesthesiologists (ASA) score of 3 or 4, which represents a patient with severe or extreme systemic disease. Anesthesia type varied among THA procedures including 11 combined spinal–epidural, 2 combined general anesthesias and epidural, 1 combined spinal–epidural with general, and 1 general anesthesia only. It should be noted that the lung transplant patients undergoing general anesthesia did so for either underperforming regional nerve blocks or the preference of the patient or anesthesiologist. Total hip arthroplasty was performed utilizing multiple approaches: posterior (7 cases), direct lateral (6 cases), and anterolateral (2 cases). All acetabular components were uncemented DePuy Pinnacle (Warsaw, IN) hemispherical cups ranging in size from 50 to 56. Femoral stems were also uncemented in all procedures and included 12 Depuy Summit and 3 DePuy Corail (Warsaw, IN). Femoral heads ranged from size 32 to 36. Average estimated blood loss was 353 (150–700) mL with no reported intra-operative complications. Total anesthesia time, defined from start of pre-operative medication administration to patient hand-off in the post-anesthesia care unit, averaged 171 (89–283) min. The hospital course was complicated in 4 hips including electrolyte imbalances (2 patients), acute renal insufficiency (1 patient) resolving with medical management, and colonic perforation (1 patient) resulting in emergent sigmoid resection with placement of a colostomy (Fig. 1). Blood transfusion for clinically symptomatic anemia (defined by hematocrit b 25 L/L and signs of anemia including tachycardia, orthostasis, or light-headedness) was performed after 10 procedures with an average of 1.9 (1–4) units given. Length of stay was 4.1 (2–16) days with final disposition of 12 hips returning to home and 3 hips needing extended care (skilled nursing or acute rehabilitation facilities).

Table 1 Lung Transplant Patient Characteristics and Outcomes After Primary THA. Patient

Side

Intervala (mos)

Joint Indication

Anesthesia Type

F/U (mos)

Death

Final HHS

Perioperative Complications

1 1 2 3 4 4 5 6 7 7 8 8 9 9 10

R L R L L R L R L R R L L R L

48 60 60 33 31 36 63 4 24 42 21 26 25 27 22

AVN AVN AVN OA AVN AVN OA AVN AVN AVN OA OA AVN AVN Fracture

CSE CSE CSE CSE CSE CSE CSE GETA, Epidural GETA, CSE GETA CSE CSE CSE CSE GETA, Epidural

56 44 46 46 7 2 24 10 37 19 25 20 24 22 14

No No No Yes No No No Yes Yes Yes No No No No Yes

71.02 71.02 87.02 82.87 76.02 76.02 72.02 N/A 89.02 89.02 89.02 89.02 90.88 90.88 82.88

None None Hyponatremia None None None Hyperkalemia Colonic perforation None None None None None Acute renal insufficiency None

a Interval = time from lung transplantation to total joint arthroplasty; F/U = follow-up time; R = right; L = left; AVN = avascular necrosis; OA = osteoarthritis; CSE = combined spinal epidural; GETA = general endotracheal anesthesia.

C.K. Ledford et al. / The Journal of Arthroplasty 29 (2014) 11–15

7/4/2006

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•Bilateral lung transplant for COPD •Post-operative complicated by prolonged ventilator dependece

•Pulmonary transplant service and anesthesia preoperatively cleared for THA 10/3/2006

• Right THA performed with no intraoperative complications 10/10/2006

10/16/2006

10/26/2006 5/29/2007

8/14/2007

• Perforated sigmoid diverticulitis resulting in emergent laparotomy with sigmoid resection with end colostomy

•Discharged following primary joint surgery •4 separate hospital admissions for Respiratory Distress, Anemia, Chest Pain, and Pneumonia

•Withdraw of care and death following progressive respiratory failure secondary to diffuse pneumonia

Fig. 1. Timeline of events for Patient #6 following THA.

Postoperative clinical follow-up was available at an average of 27.5 (2–56) months in all but one patient who died before standard clinical follow-up could be obtained. Patients subjectively self-reported their overall outcome as excellent (7 hips) and good (7 hips). Preoperative HHSs of 45.1 (30.0–55.7) increased to 88.7 (71.0–90.9) representing a “good” result [14]. Pain scores, according to the VAS, decreased as well from 5.2 (4–10) preoperatively to 1.8 (0–4). There were no periprosthetic infections or revision surgeries performed. Mortality, as defined by documented death or imminent death after hospice placement, was found in 3 patients (4 hips) from respiratory failure at approximately 23 (10–37) months following THA and 43 (14–61) months total from time of transplant. Interestingly, 2/3 patients who died also had undergone general anesthesia at the time of the arthroplasty. Lung Transplant Patients With Total Knee Arthroplasty Five primary TKAs were performed in 4 patients after lung transplantation (Table 2) including 3 females and 1 male. Indications for lung transplant were pulmonary fibrosis (3 patients) and pulmonary hypertension (1 patient) at an average age of transplant of 58.0 (50–66) years old. Interval between transplant and arthroplasty was 46.8 (29–81) months. TKA was performed at an average

age of 62.0 (52–71) years old for osteoarthritis in 3 knees and osteonecrosis in 2 knees. Again, comorbidities in this cohort were similar including pulmonary compromise (all 4 patients), hypertension (3 patients), chronic kidney disease (2 patients), diabetes mellitus (2 patients), and coronary artery disease (1 patient). The average body mass index was 27.7 (22.8–32.6) kg/m 2. All patients received an ASA score of 3 and the most common anesthesia type was a spinal regional (3 knees) followed by combined general anesthesia with regional femoral nerve block (2 knees). Total knee arthroplasty was performed using a standard medial parapatellar approach with cement fixation and patellar resurfacing in all patients. The Zimmer Natural Knee (Warsaw, IN) was used in Patient #1 while all other patients received the DePuy PFC Sigma (Warsaw, IN). Tourniquet time ranged from 92 to 119 min and estimated blood loss averaged 120 (50–300) mL. In Patient #1, an intraoperative femoral-sided MCL-sleeve avulsion occurred that was directly repaired with suture and the patient placed in a hinged knee brace postoperatively. One hospital-related complication reported was thrombocytopenia resulting in discontinuing the institution’s standard pharmaceutical anticoagulation and being discharged with mechanical prophylaxis for home use. Blood transfusion was performed after 4/5 TKAs with an

Table 2 Lung Transplant Patient Characteristics and Outcomes After Primary TKA. Patient

Side

Intervala (mos)

Joint Indication

Anesthesia Type

F/U (mos)

Death

KSSb Objective

KSS Functional

1 2 3 4 4

R R L L R

56 81 34 29 34

OA OA OA AVN AVN

Regional, GETA Spinal, Regional GETA, Regional Spinal, Regional Spinal, Regional

23 17 63 58 53

Yes No No No No

81 94 95 95 95

80 100 90 90 90

F/U = follow-up time; R = right; L = left; AVN = avascular necrosis; OA = osteoarthritis; GETA = general endotracheal anesthesia. a Interval = time from lung transplantation to total joint arthroplasty. b KSS = Knee Society Score obtained postoperatively.

Complications MCL sleeve avulsion None None Infection requiring 2-stage revision None

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average of 2.5 (2–4) units given. Length of stay was 3.6 (3–6) days with 3 patients returning home and 2 requiring an extended care facility. Postoperative clinical follow-up was available in all 5 knees at an average of 42.8 (17–63) months. Patients reported their outcomes as good (3 knees) or excellent (2 knees). There was no significant difference between pre-operative and post-operative range of motion in all knees. Objective KSS increased from 58.2 (57–64) to 92 (81–95) and functional KSS increased from 62 (50–70) to 92 (81–95) — both representing excellent outcomes according to the grading system [15]. One knee (Patient #4 left) became infected 32 months after index procedure and required a 2-stage revision. Despite the additional revision surgery, the patient still reported excellent outcomes. Finally, one TKA patient died 23 months following her joint procedure from decompensated respiratory failure. Discussion With improved techniques, refined immunosuppressive strategies and multidisciplinary care teams, lung transplantation is increasingly common and successful. As the number of living lung transplant recipients continues to grow, there will be an increased frequency of orthopaedic care for hip and knee degenerative osteoarthritis or osteonecrosis in order to improve quality of life similar to that of the cardiac transplant population [16,17]. According to our results, these patients can expect to experience significant improvement in functional outcome scores. The interval increase in HHS of 43.6 and final postoperative HHS of 88.7 are comparable to published scores in the renal [8], cardiac [10,11] and liver transplant populations [18]. Similarly, the significant increase in the KSS to a final objective and functional score of 92 also resembles prior transplant cohorts [7,11]. Despite successful clinical outcomes, major elective orthopaedic procedures in this population are not without risk, and perioperative medical management requires a multidisciplinary approach. At our institution, it is our policy to directly involve the pulmonary transplant medicine service in the post-operative care of these patients. Out of all 14 patients (15 hips, 5 knees), 4 patients experienced minor perioperative complications including electrolyte disturbances (2), AKI (1), and thrombocytopenia (1), all of which resolved with appropriate medical management. One THA patient experienced a major perioperative complication, colonic perforation requiring emergent surgical intervention and prolonged hospitalization. The patient was ultimately able to be discharged, but experienced a number of further medical admissions over the next several months for pulmonary compromise and ultimately died 10 months postoperatively. Interestingly, this was the only patient in this series with a preoperative ASA score of 4. The transfusion rate in this series was relatively high with 10/15 hips (66%) and 4/5 knees (80%) receiving a blood transfusion for symptomatic anemia. In contrast, Aminata et al [13] reported a 13/33 (39.4%) transfusion rate after THA in liver transplant patients. Our decision to transfuse was based on clinical symptoms and in conjunction with the recommendations of the pulmonary transplant medicine service. This likely reflects the relative inability of lung transplant patients to tolerate even minor fluctuations in hemoglobin levels post-operatively in the setting of restricted pulmonary function. As to be expected, length of stay in this population was slightly higher (4.1 for THA and 3.6 for TKA) than uncomplicated primary arthroplasty at our institution, which averages 3.3 and 3.4 days for THA and TKA respectively over the same time period. Given the significant comorbidities of the patients, we believe this relative increase to be not unreasonable and credit the pulmonary transplant medical specialists for their inpatient recommendations to facilitate a safe and efficient hospital stay. There was only one case of periprosthetic infection in a TKA patient who experienced an acute infection 18 months after the index procedure with coagulase negative Staphylococcus. The source was

presumed to be hematogenous and the patient was treated initially with irrigation, debridement and polyethylene liner exchange followed by an extended course of intravenous antibiotics. However, his infection recurred and he later underwent successful treatment with a two-stage revision with excellent outcomes. Nowicki and Chaudhary [19] reviewed reported infection rates of THA in renal transplant patients with rates varying significantly from no increased risk to rates up to 19%. They concluded that such wide variance makes it difficult to establish a definitive consensus. Furthermore, a paucity of literature exists on infection rates in other transplant cohorts undergoing total joint arthroplasty validating previous assertions that fear of early or late infection may be unjustified in these immunocompromised patients [6,20]. Mortality at time of final follow-up was also seemingly high including 4 of 14 patients (4 hips, 1 knee). The interval time of transplant and time of arthroplasty to death averaged 50.2 and 20.6 months respectively. Current unadjusted median survival rates following pulmonary transplant are estimated to be 79% at 1 year, 64% at 3 years, 53% at 5 years, and 30% at 10 years with certain degrees of variation according to baseline patient demographics, comorbidities, and condition of donor lungs [1]. Our patient survival rate of 71.8% (10/14 patients) at a median follow-up of 30.5 months (2.5 years) appears to be comparable to these results. While it is difficult to make specific conclusions based upon this small patient cohort, the reality of shortened life expectancy must be discussed with individual lung transplant patients prior to performing elective joint arthroplasty. The weaknesses of this study include its retrospective design, small patient population, and short follow-up. Nonetheless, while numerous studies have evaluated other solid organ transplant populations, there does not appear to be any prior report of outcomes following elective THA and TKA in lung transplant patients. The results of the study suggest that total hip and knee arthroplasty can be safely performed and provide good functional outcomes in lung transplant recipients. These patients should be informed of inherent risks related to postoperative complications and survival rates; but such risks do not appear to be any further increased than other transplant cohorts undergoing arthroplasty. We do recommend multidisciplinary care teams to include a pulmonary transplant medical specialist to optimize the patient preoperatively and continue to follow postoperatively to minimize acute complications and length of stay while maximizing overall outcomes. References 1. Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart–lung transplant report—2012. J Heart Lung Transplant 2012;31(10):1073. 2. Demirors H, Kaya A, Akpinar S, et al. Effect of long-term steroid use on prognosis for patients with surgically treated avascular necrosis of the hip. Transplant Proc 2002;34(6):2114. 3. Schoch OD, Speich R, Schmid C, et al. Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor. Transplantation 2000;69(8):1629. 4. Bia M. Evaluation and management of bone disease and fractures post transplant. Transplant Rev (Orlando) 2008;22(1):52. 5. Deo S, Gibbons CL, Emerton M, et al. Total hip replacement in renal transplant patients. J Bone Joint Surg Br 1995;77(2):299. 6. Cheng EY, Klibanoff JE, Robinson HJ, et al. Total hip arthroplasty with cement after renal transplantation. Long-term results. J Bone Joint Surg Am 1995;77(10):1535. 7. Boquet J, Goffin E, Poilvache P. Outcome of total knee arthroplasties after renal transplantation. Arch Orthop Trauma Surg 2008;128(12):1345. 8. Lim BH, Lim SJ, Moon YW, et al. Cementless total hip arthroplasty in renal transplant patients. Hip Int 2012;22(5):516. 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. Leon JL, Resines C, Zafra A. Total hip arthroplasty in heart transplant patients. Acta Orthop Belg 2007;73(6):720. 11. Leonard GR, Davis 3rd CM. Outcomes of total hip and knee arthroplasty after cardiac transplantation. J Arthroplasty 2012;27(6):889. 12. Levitsky J, Te HS, Cohen SM. The safety and outcome of joint replacement surgery in liver transplant recipients. Liver Transpl 2003;9(4):373. 13. Aminata I, Lee SH, Chang JS, et al. Perioperative morbidity and mortality of total hip replacement in liver transplant recipients: a 7-year single-center experience. Transplantation 2012;94(11):1154.

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