Abstract
Background:
The study purpose was to (1) evaluate health-related quality of life (HRQL) with the PROSthesis of Antibiotic Loaded Acrylic Cement (PROSTALAC) in situ for infected total hip arthroplasty (THA), (2) determine infection resolution, and (3) compare subjects who underwent second stage surgery with those who retained the PROSTALAC on a longer term basis.
Methods:
Demographics, physical demand level, and comorbidities were recorded prospectively in 29 subjects followed to at least 24 months after initial PROSTALAC insertion. HRQL was evaluated using the Western Ontario McMaster Osteoarthritis Index (WOMAC) and RAND 36-Item Health Survey. Infection resolution was determined using a pre-specified clinical definition.
Results:
Twenty-five of 29 (86%) subjects’ infections resolved. Three subjects died, of whom two had resolved infections. For survivors, 22/26 (85%) completed HRQL evaluations. After PROSTALAC insertion, pain and function improved within 3–6 months and was retained at 24 months. Of those followed to 24 months, 7/22 (32%) subjects underwent second stage surgery. They were higher physical demand subjects (p = 0.03) than those not undergoing second stage surgery. We found no difference in WOMAC scores at 24 months between those who underwent second stage surgery and those who retained the PROSTALAC (p > 0.32).
Discussion:
The PROSTALAC system for THA appears to allow acceptable HRQL while in situ for at least 2 years in low physical demand patients. Subjects with higher physical demand levels are more likely to undergo second stage surgery.
Conclusion:
Further evaluation is required to determine whether longer term PROSTALAC retention may be appropriate for specific patient groups.
Keywords
Introduction
Periprosthetic joint infection (PJI) following total hip arthroplasty (THA) results in substantial morbidity and increased healthcare utilization. 1 –4 The options for treating PJI include retaining the original prosthesis with medical treatment of infection or removal and reimplantation of a new prosthesis in a single or two-stage procedure. In two-stage procedures, the infected hip is debrided, the prosthesis removed, and an antibiotic-impregnated spacer is inserted. 2,4,5 The infection is concurrently treated with oral or intravenous (IV) antibiotics, followed by second stage reimplantation once infection resolves.
For two-stage procedures, the PROSthesis of Antibiotic Loaded Acrylic Cement (PROSTALAC) system (Depuy, Warsaw, Indiana, USA) is an accepted method of treating PJI. 6 –8 The PROSTALAC facilitates infection resolution while concurrently providing patients with acceptable function and retaining soft tissue tension prior to reinsertion of new prostheses. 9,10 Although designed as a temporary spacer, 8,11 a few studies with a limited number of patients have reported successful retention of cement spacers on a longer term basis. 12 –14
We previously evaluated infection resolution and health-related quality of life (HRQL) with the PROSTALAC in situ using a retrospective, cross-sectional design. 10 The primary objective of this prospective longitudinal study was to report HRQL with the PROSTALAC in situ and then following second stage surgery for patients with infected THA. Secondarily, we evaluated infection resolution. As many subjects did not proceed to second stage surgery, a tertiary objective compared subject characteristics and outcomes between those who did and did not proceed to second stage THA reimplantation following PROSTALAC insertion.
Materials and methods
Design
A prospective series of subjects were identified preoperatively for PJI in a large regional health zone where over 3000 total joint arthroplasties are performed annually. No sample size calculation was performed. The study was approved by the Health Ethics Review Board (Pro00001126).
Subjects
Subjects were eligible if they presented for management of PJI after primary THA, had preoperative blood work, completed preoperative evaluation of HRQL, and provided signed informed consent. Infection was diagnosed using the following criteria: C-reactive protein (CRP) greater than 10 mg/l and erythrocyte sedimentation rate (ESR) greater than 30 ml/h and/or bacterial growth from aseptically collected deep cultures obtained from hip aspiration.
Subjects with a native hip infection or who were undergoing treatment for a hip fracture, had a creatinine clearance of less than 30 ml/min, required further surgery for a PJI, or were unable/unwilling to complete follow-up visits were excluded.
Enrolment
Preoperatively a research associate obtained informed consent and ascertained medical history, including comorbidities, and information regarding their THA. Subjects were also rated as “low,” “moderate,” or “high” physical demand based on their age, weight, health status (i.e. American Society of Anaesthesiologists rating), and pre-revision activity level. Subjects completed HRQL questionnaires consisting of the joint specific Western Ontario McMaster Osteoarthritis Index (WOMAC) and the generic health status RAND 36-Item Health Survey (RAND-36).
Operative intervention
All subjects had the primary THA prosthesis removed with the hip debrided and copiously irrigated with a mean of nine (±1.3; range 6–12) litres of saline. Several tissue samples (and fluid, where possible) were obtained intraoperatively and sent for microbiological culture.
Subjects received a PROSTALAC with a standardized antibiotic regimen. The PROSTALAC consists of a cobalt-chrome femoral stem covered with antibiotic-loaded cement, a cobalt-chrome ball, and a polyethylene acetabular component. The attending surgeon created and inserted the PROSTALAC according to the manufactures’ instructions, while accounting for bone loss and defects. Of 29 subjects, 22 (76%) had a posterior approach, 4 (14%) had a Hardinge approach, and 3 (10%) subjects did not have the approach specified. Sixteen (55%) subjects had an extended trochanteric osteotomy performed while 10 (35%) did not; again 3 (10%) subjects did not have this information specified.
For each 40 g bag of cement used, Simplex™ P with tobramycin (Howmedica International S.de R.L., Limerick, Ireland) cement containing 1 g of tobramycin was used along with 2.4 g of additional tobramycin and 1.0 g of Vancomycin. Of 29 subjects, 24 (83%) received the prescribed regimen. For the remaining five (17%) subjects, the operative form was missing cement type, number of vials or bags of cement that did not allow calculation of dose/bag. Subjects were monitored for renal and/or vestibular complications associated with drug toxicity; no such complications were reported.
Infection management
Subjects were followed by an infectious diseases specialist and their surgeon. Appropriate IV and/or oral antibiotic therapy was administered on an inpatient basis and subjects completed a 6-week course of IV antibiotic therapy on an outpatient basis as appropriate. If there was still evidence of infection after 3 months, a second surgery was performed with reimplantation of a new PROSTALAC, followed by another course of appropriate IV and/or oral antibiotic therapy. Long-term antibiotic suppression was offered if the subject was a poor surgical risk for another surgery. If the infection persisted after the second PROSTALAC insertion, subjects had a Girdlestone procedure and/or were placed on long-term antibiotic suppression.
Postoperative follow-up
Operative and antimicrobial therapy were recorded in and out of hospital. It was anticipated that subjects would be reevaluated 3 months and potentially 6 months postoperatively with the PROSTALAC in situ. Following second stage reimplantation, subjects were to be reevaluated 6, 12, and 24 months postoperatively.
During follow-up, many subjects, in discussion with their orthopedic surgeon, elected to keep the PROSTALAC as their definitive prosthesis and did not undergo second stage surgery. These decisions were based on patients’ satisfaction with current pain and function levels as well as their high risk for postoperative complications due to their health status. At each follow-up, surgeons and patients discussed the need/desire for further surgery.
Thus, follow-up for these subjects was revised to 3, 6, 12, and 24 months and then annually with the PROSTALAC in situ. Subjects who underwent second stage surgery were followed at 6 months postoperatively, then annually until 24 months. At each visit, all subjects completed HRQL questionnaires and medical complications were recorded.
Outcomes
The primary study outcome was joint-specific HRQL (pain, function, and stiffness) measured by the WOMAC. The WOMAC has been shown to be valid, reliable, and sensitive to change in patients receiving a THA. 15,16 Each WOMAC subscale score was transformed to a range from 0 to 100 points, with a score of 100 indicating no pain or dysfunction, so that the RAND-36 and WOMAC scores were unidirectional. 17
The secondary study outcome was overall health status measured by the RAND-36. The RAND-36 contains identical items as the Short Form 36 but has no licensing fee and has been tested for validity and reliability in THA patient populations. 16,18,19 Due to the small number of subjects, we reported only the physical and mental health summary scores.
The tertiary study outcome was infection resolution, defined as negative intraoperative periprosthetic tissue cultures at second stage procedure with normalization of inflammatory markers, that is, CRP and ESR. For those not undergoing a second procedure, negative joint fluid aspiration cultures and/or the absence of clinical infection (pain, sinus, prosthesis loosening) with normalization of CRP and ESR were used as indicators of infection resolution.
Analysis
Descriptive statistics were performed for all variables. Self-reported WOMAC pain, function, and stiffness scores and the two RAND-36 summary scores were assessed over time using repeated measures analysis of variance (ANOVA). To compare those proceeding to second stage surgery to those retaining the PROSTALAC, two-way repeated measures ANOVA was used to compare preoperative and 24-month results between groups over time. All statistical analyses were performed with the Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, Illinois, USA) utilizing two-tailed tests and a significance level of α = 0.05. A significance level of p ≤ 0.10 was deemed as representing a trend.
Results
Enrollment
Twenty-nine subjects between 39 and 89 years were enrolled (Table 1). The median time to infection from primary THA was 4.1 years ranging from 1 month postoperative to greater than 16 years postoperatively. Most subjects were low physical demand subjects with greater than three comorbidities and an average body mass index (BMI) of 31.4 ± 7.7 (Table 1). The most commonly reported comorbidities were arthritis (n = 24; 83%) and hypertension (n = 17; 59%). Seven (24%) subjects had diabetes mellitus.
Baseline characteristics of subjects undergoing PROSTALAC insertion for management of a PJI.
SD: standard deviation; IQR: interquartile range; WOMAC: Western Ontario McMaster Osteoarthritis Index; RAND-36: RAND 36-Item Health Survey; PROSTALAC: PROSthesis of Antibiotic Loaded Acrylic Cement; PJI: periprosthetic joint infection.
Subjects also reported poor joint-specific HRQL pre-PROSTALAC with reduced function and moderate pain and stiffness levels (Table 1). Finally, subjects reported that their PJI negatively impacted their overall physical health based on the RAND-36 summary scores (Table 1).
Follow-up
Three subjects died and four additional subjects withdrew prior to 24 months. Of the remaining 22 subjects, only 7 (32%) underwent second stage surgery at a median of 11.5 months (interquartile range (IQR) 6.4, 20.3) after the initial PROSTALAC insertion. Of 11 subjects who retained the PROSTALAC and provided information past 24 months, 4 (18%) subjects were followed to 3 years, 4 (18%) to 4 years, and 3 (14%) subjects completed 5 years of follow-up.
Infection resolution
The most common organism was coagulase-negative Staphylococcus (n = 11; 38%) followed by Staphylococcus aureus (n = 5; 17%). In five (17%) subjects, no organism was identified, but frank purulent material was found intraoperatively with elevated CRP and ESR, so these subjects were included.
Three subjects required a second PROSTALAC. Of these subjects, one subject had their infection resolve and proceeded to second stage surgery, while the remaining two subjects received Girdlestone procedures and long-term antibiotic suppression.
Overall, 25 of 29 (86%) subjects’ infections resolved. Of the four that did not, one died within 3 months of surgery due to cancer that was detected postoperatively and the others (including the two previously described above) were treated with Girdlestone procedures and/or long-term antibiotic suppression. For the remaining two subjects who died, the cause of death was unrelated to the PJI and their infections had resolved.
WOMAC
Following PROSTALAC insertion, subjects reported substantial improvement of hip pain within 3–6 months, which was sustained 24 months postoperatively (Table 2). Hip function followed a similar trajectory with improvements noted within 6 months of surgery retained at last follow-up (Table 2). Hip stiffness showed the least improvement after PROSTALAC insertion. Hip stiffness at 24 months was at least equivalent to preoperative levels (Table 2). Those who had an extended trochanteric osteotomy reported similar pain (p = 0.82) and stiffness (p = 0.80) at the 6-month follow-up to those who did not. Function trended towards being better in those without a trochanteric osteotomy at 6 months (p = 0.07), but the group differences were below the minimal clinically important difference published for the WOMAC. 20
HRQL scores of 22 subjects over time.a,b
SD: standard deviation; WOMAC: Western Ontario McMaster Osteoarthritis Index; RAND-36: RAND 36-Item Health Survey; HRQL: health-related quality of life.
aValues in italic indicate significant at p < 0.05.
bAnalyzed using a Repeated Measures Analysis of Variance.
cCompares change over time (preoperative, 3–6 months, up to 24 months). Time 1: preoperative to 3–6 months; time 2: 3–6 months to 24 months.
For the 11 (38%) subjects with the PROSTALAC in situ for 3–5 years postoperative, the median pain score was 65.0 (IQR 55.0, 75.0), the median function score was 60.0 (45.59, 67.65), and the median stiffness score was 50.0 (50.0, 75.0), suggesting deterioration over time, particularly with stiffness. None of these subjects wanted further surgery.
RAND-36
For the RAND-36, there were statistically significant improvements (p = 0.02) in the physical health summary score, but no changes in the mental health summary score (p = 0.51) (Table 2). In subjects followed after 24 months, the median physical health summary score decreased to 29.1 (23.0, 31.1), while the median mental health summary score was relatively unchanged 59.3 (38.2, 62.0).
Retaining PROSTALAC versus proceeding to second stage surgery
The seven subjects proceeding to second stage surgery were more likely to be high physical demand subjects (p = 0.03) and tended to be younger with an average age of 58.1 ± 16.0 years versus an average age of 71.5 ± 9.8 years for those retaining the PROSTALAC (p = 0.07). There were also trends for males (p = 0.08), those with lower BMI (p = 0.10) and having fewer comorbidities (p = 0.07) to proceed to second stage surgery (Table 3).
Comparison of subjects retaining PROSTALAC long-term versus subjects proceeding to second stage surgery.a
SD: standard deviation; WOMAC: Western Ontario McMaster Osteoarthritis Index; RAND-36: RAND 36-Item Health Survey; ANOVA: analysis of variance; PROSTALAC: PROSthesis of Antibiotic Loaded Acrylic Cement; HRQL: health-related quality of life.
aValues in italic indicate significant at p < 0.05 or trending at ≤0.10.
bAnalyzed using independent T-tests.
cAnalyzed using χ 2 tests.
dAnalyzed using two-way repeated measures ANOVA; group interactions not significant and not reported; time effect reflects the change in scores over time; group effect compares group differences.
Prior to PROSTALAC insertion, subjects proceeding to second stage surgery had similar hip pain, function, and stiffness as those retaining the PROSTALAC long-term. At the 24-month evaluation, there had been improvement over time in all three WOMAC dimensions and although those undergoing second stage surgery had greater gains than those who retained the PROSTALAC, these differences were not statistically significant between groups (Table 3).
Subjects in both groups reported similar physical health summary scores preoperatively. Again, both groups reported improvements over time with those proceeding to second stage surgery reporting large improvements, but these group differences were not statistically significant (Table 3). Overall, mental health summary scores did not change significantly over time nor were they significantly different between groups (Table 3).
Discussion
The PROSTALAC system is effective for treating PJI and providing improved HRQL during treatment. 3,5,8,11,21,22 To our knowledge, this is the largest series of subjects retaining a PROSTALAC as a potentially definitive prosthesis. A single-stage approach with long-term PROSTALAC retention may represent a feasible option for lower physical demand subjects or for older patients with multiple comorbidities who may be a poor surgical risk, but our results should be considered preliminary and likely require verification in larger studies from other centers.
We previously demonstrated in a retrospective review that a subject with a PROSTALAC in situ reported improved pain and function relative to that reported by patients waiting for THA. 10 However, the PROSTALAC subjects reported more pain and lower function than would be expected 6 months after a primary THA. 10 The current prospective study found that patients with an active PJI report increased pain and decreased function prior to PROSTALAC insertion. Following the PROSTALAC, these health dimensions improved markedly within 3–6 months.
These reported improvements were retained to 24 months after PROSTALAC insertion even when patients did not proceed to second stage surgery. Many patients with a PJI are similar to those in our study. They have multiple comorbidities and are at high risk for perioperative complications. The PROSTALAC may be a more definitive treatment option for those patients who are not able to live an active life style and who do not want further surgery. However, further research is required to determine the long-term outcomes of PROSTALAC retention and when long-term retention of a PROSTALAC may be appropriate. We also had a limited number of subjects followed up to 5 years postoperatively, and although HRQL scores did deteriorate over time, no subject was considering further surgery.
We believe that this is the largest patient series reporting HRQL with the PROSTALAC in situ for an extended period. Others have noted similar results up to 4 years in small numbers of patients. 12 –14 Similar to our study, those subjects tended to be lower demand subjects who were poor surgical risks. Further research is required as it would be important to better characterize what subjects may be appropriate for consideration of this management approach.
Our study was prospective and used standardized assessment tools that incorporated patient physical demands. Having subjects who either retained the PROSTALAC or proceeded to second stage surgery allowed comparison of outcomes and patient characteristics, which may be helpful in designing future research studies.
However, there are limitations. Although this is the largest series of long-term PROSTALAC retention, the study group was small. Most subjects were only followed to 24 months postoperatively. Although this is longer follow-up than expected with a PROSTALAC, it is still relatively short follow-up for determining the outcomes of long-term PROSTALAC retention. We also modified our intended protocol as clinical management evolved, which may have resulted in some unintended bias. Our series is restricted to the PROSTALAC system that functions similar to a THA; thus, our outcomes may not generalize to other antibiotic spacers. Finally, we did not evaluate radiological outcomes so we cannot comment on any subsidence or loosening of the implant. However, patients were seen annually by their surgeon to ensure that the PROSTALAC was intact and functioning.
In summary, the PROSTALAC effectively managed PJI and improved HRQL within 3–6 months of surgery. It may also be a longer term solution for low demand subjects and/or those who are a poor surgical risk, but future research should evaluate patient and health characteristics in a larger series to define which patients may be appropriate for this approach, and if, in fact, this is a viable management approach.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: LA Beaupre receives salary support from the Canadian Institutes for Health Research as a New Investigator (Patient Oriented Research) and Alberta Innovates Health Solutions as a Population Health Investigator. This study was supported by unrestricted research grants from the Edmonton Orthopaedic Research Committee and Depuy/Johnson and Johnson Inc.