ORTHOPEDICS November 2011;34(11):736.
Infected Total Femoral Replacements: Evaluation of Limb Loss Risk Factors
by John S. Hwang, BS; Kathleen S. Beebe, MD; Francis R. Patterson, MD; Joseph Benevenia, MD
A complication of total femoral replacement (TFR) is periprosthetic infection. Studies have shown that infected endoprostheses have a significant amputation rate, as high as 36.7%. This study examined possible risk factors that may attribute to unsalvageable TFRs following periprosthetic infections, including age, sex, primary vs secondary TFRs, number of irrigation and debridements, recent history of periprosthetic infection, early vs late infection, use of antibiotic cement, and the number of postoperative antibiotics. In a retrospective chart review, 10 patients who had periprosthetic infections of their TFRs were identified from our orthopedic surgical database between 2000 and 2010. Seven of 10 TFRs were unsalvageable due to infection. The 2 greatest risk factors that influenced unsalvageable TFR were age older than 50 years and recipients of secondary TFRs. All 6 patients older than 50 years had unsalvageable TFRs, whereas 1 of 4 patients younger than 50 years had an unsalvageable TFR (P<.05). Similarly, all 6 patients who received secondary TFRs had unsalvageable TFRs, whereas 1 of 4 patients who received a TFR as the primary method of treatment had an unsalvageable TFR (P<.05). No other risk factors showed statistical significance or could be identified as possible risk factors. Surgeons should educate patients who fall into high-risk categories about the benefits of early intervention, such as amputation, that could prevent additional surgeries and decrease the lengths of hospitalizations.
Mr Hwang and Dr Beebe are from the Department of Orthopaedic Surgery, and Drs Patterson and Benevenia are from the Division of Musculoskeletal Oncology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey.
Mr Hwang and Drs Beebe, Patterson, and Benevenia have no relevant financial relationships to disclose.
Correspondence should be addressed to: Kathleen S. Beebe, MD, Department of Orthopaedic Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103 (firstname.lastname@example.org).
Posted Online: November 09, 2011
With continuing advances in medical technology, limb salvaging has become a more common method of treatment in the orthopedic field. One method that has significantly benefited from recent advances is the use of implants after a large resection of bone that is typically caused by large bone neoplasms. Because the femur is one of the most common sites of primary bone sarcomas, 1-4 treatment of large femoral tumors was previously limited to hip disarticulation or hemipelvectomy. 5 Advancements in endoprosthetic implants, chemotherapy, radiation, and diagnostic imaging have allowed for massive bone resection of the femur caused by primary bone tumors to be treated with total femoral replacements (TFRs). 1,6-8 Total femoral replacement has not been limited to massive oncologic resections but has also found an application in nononcologic indications, such as failed total hip arthroplasty, osteomyelitis, and failed internal fixation. 5,9 Although no evidence of improvement in either quality of life or survival following limb salvage procedures exists, some studies have shown improvements in cost-effectiveness and overall function of the salvaged limbs. 7,8,10,11
Although TFR is an orthopedic advancement, this method has complications. One of the most unfavorable complications of TFR is failure due to acute or chronic periprosthetic infection. 6,7,12,13 However, to the authors’ knowledge, no studies that analyzed the possible risk factors for unsalvageable TFRs in individuals with periprosthetic infection have been published.
Materials and Methods
Approval for a retrospective chart review was obtained from the institutional review board, and data were collected from the New Jersey Medical School Orthopaedic Department surgical database from the years 2000 to 2010; 10 patients met the inclusion criteria of the study. The inclusion criteria of the study consisted of individuals with TFRs who subsequently were identified as having periprosthetic infections. Periprosthetic infection was defined as (1) the presence of a growth of microorganisms from a pre- or intraoperative joint aspiration; (2) purulence surrounding the prosthesis at the time of surgery; or (3) acute inflammation consistent with infection on histopathological examination. 14
Early infection was defined as periprosthetic infection occurring within 3 months of TFR surgery, whereas late infection was defined as an infection occurring 3 months after surgery. Recent history of infection was defined as an infection that was present within 6 months prior to the TFRs. Patients received either primary or secondary TFRs. Primary TFRs were defined as those performed in individuals who received a TFR as the primary method of treatment for the disease. Secondary TFRs were defined as TFRs that were implanted due to primary implant failure and further surgical or medical intervention to retain the patient’s primary implant was considered ineffective. The standard surgical technique for primary or revisional TFR was used on all patients.
The information collected from the 10 identified patients included age, primary diagnosis, hospital course, surgical management, and follow-up. These cases were divided into 2 groups: unsalvageable TFRs and salvageable TFRs. An unsalvageable TFR was defined as an infected TFR that resulted in a hip disarticulation, hemipelvectomy, or removal of the TFR with no ability to reimplant the endoprosthesis. A salvageable TFR was defined as an infected TFR that was successfully retained. The indications for amputation were for patients who had infected TFRs that could not be managed by antibiotics or surgery and further surgical or medical intervention was deemed to be ineffective.
Statistical analysis was performed using the Fischer’s exact test, and a P value of <.05 was considered statistically significant when risk factors were assessed.
There were 24 patients with TFRs seen at our institution between 2000 and 2010. Fourteen of these patients were not included in this study due to a lack of history of periprosthetic infection. Of the 10 patients who had TFRs with periprosthetic infections, 5 were women and 5 were men and their mean age was 44.3 years (range, 9-78 years).
Four of the tenpatients received primary TFRs. Three of these patients were diagnosed with osteosarcoma, and 1 was diagnosed with Ewing’s sarcoma. Six patients received secondary TFRs. Of these, 4 had failed total hip arthroplasties secondary to periprosthetic infection, 1 had a failed proximal femoral replacement secondary to aseptic loosening, and 1 had a failed distal femoral replacement secondary to periprosthetic fracture. Mean postoperative follow-up for the patients with infected TFRs was 10.5 months (range, 3-22 months). Patients who had unsalvageable TFRs had a mean of 12 weeks from last surgery to amputation. For the 3 patients with salvaged TFRs, follow-up time following treatment of the infection was 6, 34, and 36 months, respectively. One patient succumbed to his primary disease, osteosarcoma, within 6 months of his periprosthetic infection.
In 9 of 10 patients, positive cultures were found consisting of the following microorganisms: coagulase-negative Staphylococci (n=4), Enterococcus species (n=3), Staphylococcus aureus (n=1), and Pseudomonas aeruginosa (n=1). The 1 patient with negative cultures had histological evidence of osteomyelitis, as well as pain and persistent fluid collection around the TFR.
Seven of 10 unsalvageable TFRs were due to infection. The 2 greatest risk factors for unsalvageable TFRs were age older than 50 years (Figure 1) and recipients of secondary TFRs (Figure 2). All 6 patients older than 50 years had unsalvageable TFRs, whereas 1 of 4 patients younger than 50 years had an unsalvageable TFR (P<.05). Similarly, all 6 patients who received secondary TFRs had unsalvageable TFRs, whereas 1 of 4 patients who received a primary TFR had an unsalvageable TFR (P<.05). All results are shown in the Table.
||Figure 1: Percentage of salvageable and unsalvageable TFRs in patients younger than 50 years vs patients 50 years and older.
||Figure 2: Percentage of salvageable and unsalvageable TFRs in primary vs secondary TFRs.
||Table: Results of Risk Factor Analysis for Unsalvageable TFR Following Periprosthetic Infection
Sex, number of irrigation and debridements, recent history of a periprosthetic infection, early vs late periprosthetic infection after TFR surgery, use of antibiotic cement, and number of postoperative antibiotics did not show statistical significance and could not be identified as possible risk factors (Table).
Prior to the use of TFRs, treatment following a massive resection of the femur was limited to limb amputation, leaving patients with functional deficits of the lower limb. 6 The development of endoprosthesis in limb salvaging has allowed for the TFR to become an accepted method of treatment following large resections of the femur. This allows physicians to preserve significant function in the lower extremities of their patients. 1,9 Although no evidence of improvement in either quality of life or survival when comparing limb salvaging to amputation exists, 11 studies have shown overall functional improvement of the salvaged limbs prior to the patient having surgery. 7,8,15,16
The complexity of the TFR procedure, as well as the high-risk nature of the patient population (eg, immunocompromised individuals, elderly) in which the treatment has been used led to predictable complications. The complications typically seen with TFRs include dislocation of the hip, superficial and deep infection, periprosthetic fracture, local recurrence of tumor, and joint pain. Of these complications, tumor recurrence and deep wound infection have been shown to increase the risk of amputation. 8,17-19
Studies have shown infection rates in TFRs to be between 3% and 36.7%. 5-8,12,16,18,20 In a large study of orthopedic oncologic patients by Jeys et al, 17 the researchers reported that individuals with infected endoprosthesis had a 19% rate of amputation due to infection. Due to the lack of large TFR case studies, the percentage of unsalvageable TFRs caused by infection has never been properly addressed. Our studies demonstrated a significant number of unsalvageable TFRs following infection (70%), thus making the understanding of risk factors for unsalvageable TFR following infection important.
The current study examined multiple possible risk factors, including age, sex, secondary TFRs, number of irrigation and debridements, recent history of periprosthetic infection, early vs late infection, use of antibiotic cement, and number of postoperative antibiotics. From these variables, patients older than 50 years and receipt of secondary TFRs had the greatest risks for an unsalvageable TFR following a periprosthetic infection.
Ward et al 6 reported 3 cases of deep tissue infection in their study of 21 cases of TFRs. Two of 3 patients, both older than 50 years, needed hip disarticulations, whereas the remaining 1 (aged 26 years) resulted in a salvaged TFR. Nerubay et al 12 also reported the case of a 55-year-old patient with a deep tissue infection among the 19 cases of TFRs that could not be controlled and resulted in amputation. These studies, along with the current study, suggest that an older age poses a greater risk for unsalvageable TFR following a periprosthetic infection. The increased risk for unsalvageable TFRs following periprosthetic infection in the older population can be attributed to multiple factors (eg, decreased immuno-responsiveness, greater comorbidities, and difficulties in activities of daily life). These factors were not assessed in this study.
In a study of revision arthroplasty to TFR by Frieseke et al, 18 the researchers found the rate of unsalvageable TFRs following periprosthetic infections to be 17%, with all patients having negative cultures for microorganisms at the time of revision surgery. These patients received TFRs due to failure of their original endoprosthesis. Although our rate of unsalvageable secondary TFRs following periprosthetic infections was found to be much higher, 4 of the 10 patients in our study had a recent infection of their endoprosthesis that necessitated the need for conversion to TFRs. This factor may contribute to the higher rate of incidence of unsalvageable secondary TFRs following periprosthetic infections.
The study by Ward et al 6 on TFRs reported 8 cases of TFRs that were used following failed subtotal femoral endoprosthesis. Two of these patients had periprosthetic infections following their surgical revision to TFRs, and of these 2 patients, 1 had an unsalvageable TFR. Although both studies demonstrated lower rates of unsalvageable TFRs than the authors’ study, they both demonstrate concerning rates of unsalvageable TFRs when TFRs are used as revision surgeries and are then followed by periprosthetic infections. One possible reason for this high rate of unsalvageable TFRs could be that multiple endoprosthetic surgeries, as well as periprosthetic infections, may cause soft tissue damage, making proper soft tissue coverage difficult. Studies by Hardes et al 21 and Grimer et al 22 reported that inadequate soft tissue coverage in tumor patients with endoprosthesis poses a higher risk of implant failure following infection.
Although other risk factors were studied in the authors’ research, these did not show statistical significance. The authors note that, although not statistically significant, all individuals who had recent histories of deep tissue infections at the time of initial TFR surgery and went on to have infected TFR had unsalvageable TFRs (n=4).
There are several limitations to the current study. Due to the specific inclusion criteria of this study, the research was restricted to a small number of cases. This made enhanced statistical analyses, such as multivariant analysis, difficult. Also, it should be noted that the lack of statistical significance in multiple risk factors in this study may be the result of the limited sample size and not a clear indication that these risk factors did not at all influence the failure rates of TFRs. In addition, the small number of cases also limited the authors’ ability to assess comorbidities that influence infection, such as smoking, diabetes mellitus, and rheumatoid arthritis. Finally, this study included patients with varying diseases (oncologic and nononcologic), with each patient having a different disease process. Due to the brief follow-up time and the limited number of patients, the effect of each disease on TFRs could not be addressed.
The authors stress the importance of evaluating risk factors for unsalvageable TFRs. Patients who may fall into high-risk categories (those older than 50 years and recipients of secondary TFRs) may benefit from physician education regarding the advantages of early interventions, such as amputation, that could prevent additional surgeries and decrease the lengths of hospitalizations. In addition, preventing infection in TFRs in all patients is important, but particularly so in patients who have a higher risk for unsalvageable TFRs following periprosthetic infection.
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