Laboratory Analysis in the Assessment of Painful Total Knee Replacement


Study

Test

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

Accuracy (%)

Della Valle et al. [5]

ESR

90.2

66.0

67.3

89.7

76.6

CRP

95.1

75.5

75.0

95.2

84.0

Greidanus et al.a [6]

ESR

93.0

83.0

71.0

96.0

86.0

CRP

91.0

86.0

74.0

95.0

88.0

Either +

95.0

0.77

68.0

96.0

83.0

Both +

88.0

93.0

84.0

95.0

92.0

Bottner et al.b [2]

ESR

81.0

89.0

74.0

86.0

63.0

CRP

95.0

91.0

80.0

98.0

92.0

Fink et al. [7]

CRP

72.5

80.9

59.2

88.5

78.1

Bedair et al.c [8]

ESR

100

12

20

100
 
CRP

68

66

30

91
 

All values converted to percentage

aUsing cutoff-point ESR 22.5 mm/h; CRP 13.5 mg/L

bUsing cutoff-point ESR 32 mm/h; CRP 15 mg/L

cUsing cutoff-point ESR 38 mm/h; CRP 9.5 mg/L either + refers to simultaneous ESR/CRP with either being positive in the presence of infection and both + to simultaneous testing with both being positive



ESR and CRP are nonspecific markers of inflammation. CRP usually falls below 10 mg/L within 21 days. The ESR may remain elevated for a longer period.

The American Academy of Orthopaedic Surgeons (AAOS) has issued a strong recommendation for ESR and CRP measurement in assessing prosthetic joint infection [9]. This is based on the evaluation of several level I studies including data for periprosthetic infection in TKR [2, 57, 10].

Della Valle et al. [5] assessed 105 patients with painful TKR. Mean ESR was reported at 79.6 mm/h in the group subsequently diagnosed with infection. This was significantly greater (p < 0.001) than the noninfected group (mean 26.3). However, the ESR did range from 4 to 140 in patients with infection. Similarly, the CRP was measured at a mean of 123 in the infected group, again significantly greater (p < 0.001) than the noninfected group (mean 7.4). The range of CRP in infected cases was from 2 to 464. The combination of CRP and ESR was highly sensitive and specific (Table 26.1) with only one case of infection when both were normal.

Greidanus et al. [6] reviewed 151 knees in 145 patients presenting for revision TKR. A diagnosis of infection was established for 45 knees. Receiver operating characteristic (ROC) curve analysis was performed to determine the positivity criteria for the tests. By this method, thresholds of 22.5 mm/h for the ESR and 13.5 mg/L for the CRP were established. None of the patients included had been on antibiotic therapy during serum testing. With the use of these criteria, high levels of sensitivity and specificity were established (Table 26.1). Further, if the ESR/CRP tests were administered simultaneously and a positive result of either test was considered indicative of infection, the sensitivity was increased to 95 % although specificity decreased to 77 %. Conversely, if infection was only considered when both tests were positive, the sensitivity was lower at 88 % but specificity improved to 93 %.

It is important to understand the implications of negative and positive predictive values when reviewing the ESR and CRP in a particular case. In clinical terms, a more sensitive test may be used to rule out pathology while a more specific test may be used to increase the chance that pain is related to infection. From the study of Greidanus et al. [6], the negative predictive value of either test is 96 %, meaning there is only a 4 % chance that a symptomatic TKR is infected if both the ESR and CRP are <22.5 mm/h and 13.5 mg/L, respectively. If infection is only considered to be present if both tests are positive, the specificity is 93 % and the positive predictive value, indicating probability of infection, is 84 %.

If only one, CRP or ESR, is positive when administered simultaneously, the sensitivity for diagnosis of an infection is 95 % and specificity 77 %. If CRP and ESR tests are both positive, the specificity for diagnosis of an infection is 93 %, sensitivity is 88 %, and the positive predictive value is 84 %.

The above cutoff points for the ESR assume a manual measurement of the erythrocyte sedimentation rate using the method of Westergren. More recently, automated methods of measuring the ESR have been introduced. Using these automated methods, the reference ranges depend on the anticoagulants used in the automated test, and occasionally, values under 11 using the Westergren method may be highly abnormal with this technique. In one study [11], the correlation was good with R2 = 0.72; however, 12.5 % of patients (25/200) would have been treated differently if the automated method was relied upon. The surgeon should enquire what technique of measurement was used, and caution should be exercised if it was the automated method, particularly when the results are abnormal.



26.1.3 Interleukin-6


Interleukin-6 (IL-6) is an inflammatory cytokine secreted by white cells. It has been proposed as a screening test in combination with the CRP.

Interleukin-6 (IL-6) has been proposed as a screening test in combination with CRP. However, it is expensive and currently only an adjunct diagnostic examination.

Bottner et al. [2] evaluated IL-6 levels in patients with painful TKR and THR undergoing revision. IL-6 was significantly higher in patients with a septic joint. IL-6 and CRP were equally sensitive in this study (96.0 %), but IL-6 was less specific (87.0 % for IL-6 > 120 pg/L vs. 91.0 % for CRP ≤ 15 mg/L). IL-6 levels were found to be elevated in patients with polyethylene (PE) wear and osteolysis compared to aseptic patients without, but this was not significant (p = 0.09).

Di Cesare et al. [12] performed a similar analysis. In the setting of painful arthroplasty, IL-6 was found to have a sensitivity of 100.0 %, specificity of 95.0 %, PPV of 89.0 %, NPV of 100.0 %, and accuracy of 97 % in diagnosing infection. This was superior to the ESR and CRP in the same patient cohort.

Given the reported diagnostic characteristics of IL-6, it is plausible that combination testing using CRP and IL-6 may be a more accurate test for the detection of infection. While IL-6 may prove to be a useful adjunct in assessing painful TKR, further evaluation is required in larger patient cohorts.

Given the reported diagnostic characteristics of IL-6, it is plausible that combination testing using CRP and IL-6 may be a more accurate test for the detection of infection.


26.1.4 Other Serum Markers (Procalcitonin, TNF-α)


Several biomarkers have been investigated for their diagnostic use in the assessment of a painful arthroplasty [13].

Tumor necrosis factor (TNF)-α is an inflammatory cytokine involved in acute-phase reactions. Procalcitonin is a precursor of calcitonin and is released by the parafollicular cells of the thyroid. Usually unmeasurable in normal individuals, procalcitonin rises in response to inflammatory stimulus especially bacterial infection. Although both TNF-α and procalcitonin have been reported as highly specific for infection (94 and 98 %, respectively), neither is sensitive (43 and 33 %, respectively) [2]. Both should be considered research tools at this time.



26.2 Aspiration


Knee aspiration may be performed with a sterile technique in the operating room. Aspirated fluid should be sent for microscopic examination, cell count with white cell differential, gram stain, and microbial culture. The AAOS recommends joint aspiration of patients being assessed for periprosthetic knee infections who have an abnormal ESR and/or CRP [9]. Repeat aspiration is advised, based on consensus opinion, when (1) the clinical probability of infection is low but the initial aspiration culture is positive or (2) the clinical probability of infection is high and the initial aspiration culture is negative.

Repeat aspiration is advised when (1) the clinical probability of infection is low but the initial aspiration culture is positive or (2) the clinical probability of infection is high and the initial aspiration culture is negative.


26.2.1 Microscopy and Cell Count


AAOS guidelines indicate that a synovial fluid WCC >1,700 cells/μL or polymorphonuclear (PMN) neutrophil differential >65 % is highly suggestive of chronic infection [9]. Studies have reported variable cutoff values with WCC ranging from 1,100 to 3,000 cells/μL and PMN differential ranging from 60 to 89 % (Table 26.2).
Oct 18, 2016 | Posted by in ORTHOPEDIC | Comments Off on Laboratory Analysis in the Assessment of Painful Total Knee Replacement

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