A prospectively collected database of all patients who underwent revision total knee arthroplasty between 2000 and 2007 at the senior author’s institution was reviewed to identify patients who had clinical and radiographic suspicion of periprosthetic infections following total knee arthroplasty, and who underwent diagnostic testing with ESR and CRP laboratory values. One hundred and forty-nine of these knees had an operation for suspected periprosthetic infection. Of these knees, 113 had serological tests (ESR, CRP) performed at the time of initial presentation and treatment. The other 36 knees did not have these serological tests because they already had strong evidence of a positive deeply infected knee arthroplasty by multiple criteria as outlined below. Demographic data collected for these patients included age, gender, body mass index, and type of infection (post-operative, chronic, acute haematogenous), which are listed in Table . Approval for this study was obtained from the institution’s Institutional Review Board.
Primary diagnoses and demographic variables of the 113 patients who had erythrocyte sedimentation rate and Westergren C-reactive protein studies performed
At presentation, the senior authors evaluated them for periprosthetic infection based on clinical and radiographic findings. Radiographic findings of osteitis, osteomyelitis, or early, progressive osteolysis within two years of primary total knee arthroplasty are considered suspicious for infection. Clinical symptoms suggestive of periprosthetic infection after total knee arthroplasty include the following: a clinical history of swelling, redness, or drainage at the surgical site, and persistent, unexplained, and unrelieved pain.
The definitive diagnosis of infection after total knee arthroplasty was determined by using the Leone and Hanssen criteria for determining infection in patients with total knee arthroplasty [10
]. According to their diagnostic algorithm, one of the following four criteria were required for the diagnosis of periprosthetic infection: (1) two or more positive cultures with the same organism, (2) histological evidence of acute inflammatory response seen on intraoperative frozen section, (3) gross purulence, or (4) a draining sinus tract that communicates with the joint space. Additionally, a diagnosis of periprosthetic infection was made if greater than ten polymorphonucleocytes (PMNs) were observed on at least one intraoperative frozen histological section. Only deep incisional and joint space infections were considered periprosthetic infections; patients with haematomata or wound dehiscence that did not progress to affect the joint space were not included in this study.
To answer the first question posed in this study to determine sensitivities and specificities for ESR and CRP, the values of 10 mg/L for CRP, and 30 mm/h for ESR, were taken as cut off values. For any values greater than these, the test was considered positive for infection, and for any values less than these the test was considered negative. Sensitivities were calculated for four different combinations of tests: CRP alone, ESR alone, positive findings in ESR or CRP, positive findings in both ESR and CRP.
The second question concerned false negative rates. False negative rates were calculated to determine what percentage of patients would have been missed had these tests been used to screen for periprosthetic infection. Additionally, the above diagnostic criteria used to answer question one (CRP alone, ESR alone, CRP or ESR, CRP and ESR) were also used to stratify the results for false negative rates.
The third question again addressed false negative rates, but stratified the results by infection type. For patients with false negatives serological tests, pre-operative aspiration results were reviewed. Aspiration was not routinely performed if the patient met other criteria for infection; it was only performed pre-operatively if further verification was required or other diagnostic tests or clinical signs (i.e. Leone and Hanssen criteria, as described above) were equivocal. Leukocyte values for positive aspirations range between 1,100 and 3,000 white blood cells/mL [17
]. For the purposes of this study, aspirations were considered positive if they were greater than 3,000 white blood cells/mL. If they were between 1,100 and 3,000 cells/mL then aspirations were considered equivocal for infection. The patient population was stratified into two groups: early post-operative infections, defined as symptomatic presentation within six weeks of primary knee arthroplasty, and late infections, defined as any infection that symptomatically presented at a time later than six weeks from the initial total knee arthroplasty. Additionally, seven of the 237 knees treated for presumed aseptic failures were found to be infected at the time of surgery, and were considered latent infections, but none presented acutely and were considered late infections.
The fourth question addressed the predictive ability of ESR and CRP serological tests to accurately differentiate between two unique populations: one that has a periprosthetic infection after total knee arthroplasty, and a population of patients that are aseptic [6
]. Receiver operating characteristic (ROC) curves were used for this. ROC curves plot the sensitivity versus one minus the specificity of a given test for a set of continuous data. The continuous data is used to attempt to detect a difference between two populations having overlapping normal distributions. The ROC curve compares predictive ability using different cut-off values of a test to determine the optimal cut-off point where the most patients with the disease have a positive test, while limiting the false negative rate. The area under the curve is frequently used as a measure of how useful the test is. The closer the line is to the upper left hand corner of the graph (all true positives, with no false positives), the closer the test is to an ideal discriminator between the two groups. In this ideal situation, the area under the curve (AUC) is equal to 1; an AUC of 0.5 or less indicates decreasing usefulness in differentiating between the two groups.
Using the above-defined cut-off values, ESR and CRP values were compared versus a confirmed diagnosis of infection, to determine sensitivity and specificity. An Excel spreadsheet (Microsoft Corp., Redmond, Washington) was used for statistical analyses and the Wilson score method was used to calculate 95% confidence intervals. Additionally, receiver operating characteristic curves were generated using JMP® Statistical Discovery Software (SAS Institute, Inc., Cary, North Carolina).