The Journal of International Medical Research 2001; 29: 7 – 12 C-reactive Protein Values and Erythrocyte Sedimentation Rates after Total Hip and Total Knee Arthroplasty ÖF BILGEN1, T ATICI1, K DURAK1, O KARAEMINOĞULLARI2 AND MS BILGEN3 1Department of Orthopaedics and Traumatology, Uludağ University, Bursa, Turkey; 2Department of Orthopaedics and Traumatology, Abant Izzet Baysal University, Düzce, Turkey; 3Department of Orthopaedics and Traumatology, Sarıyer Government Hospital, Istanbul, Turkey We studied the changes in serum C- on day 21 in THR patients and at the end reactive protein levels (CRP) and of the second month in TKR patients. ESR erythrocyte sedimentation rates (ESR) in peaked on day 5 after operation (THR patients with primary osteoarthritis, who 100.5 mm/h, TKR 101.3 mm/h), dropping underwent uncomplicated arthroplasty. Of close to pre-operative values at the end of the 28 patients studied, 12 had cementless the third month in THR patients and at the total hip replacement (THR), and 16 end of the ninth month in TKR patients, underwent cemented total knee although, even after a year, ESRs were replacement (TKR) with a tourniquet. In slightly above their pre-operative values. both groups serum CRP levels increased Serum CRP levels changed more rapidly rapidly after surgery, peaking on day 2 than ESRs and returned to normal more (THR 23.17 mg/dl, TKR 26.02 mg/dl), and rapidly. CRP and ESR values tended to be dropping gradually to pre-operative values higher in TKR than in THR patients. KEY WORDS: C-REACTIVE PROTEIN; ERYTHROCYTE SEDIMENTATION RATE; ARTHROPLASTY Introduction value between 89 mg/l and 135 mg/l (mean 115 mg/l).2 There were, for example, Establishing a diagnosis of deep infection after statistically significant differences in plasma arthroplasty is difficult, and early diagnosis CRP levels but not in ESRs before revision in assists the choice of treatment and total hip prosthesis patients undergoing the likelihood of a successful outcome.1 – 4 revisions because of mechanical loosening Investigations of plasma C-reactive protein (CRP) levels and erythrocyte sedimentation (n = 23), compared with those whose rates (ESR) in patients with infected revisions were needed because of septic 2 arthroplasty have produced varied results.2,5 – 9 loosening (n = 5). ESRs reached normal levels In cases of infected arthroplasty, the within 3 – 6 months in 75 uncomplicated sedimentation level may be between 16 mm/h total hip replacement (THR) patients but and 62 mm/h (mean 35 mm/h) and the CRP always failed to reach the normal levels in 7 ÖF Bilgen, T Atıcı, K Durak et al. CRP values and ESRs after arthroplasty 18 patients with radiological and clinical To determine CRP and ESR levels, blood findings of deep infection, and there was a samples were taken before breakfast pre- statistically significant difference between the operatively, and post-operatively on days 1, 2, ESRs of the two groups.5 In a study of 229 total 3, 5, 6, 7 and 21, and at the end of the first knee replacement (TKR) patients and 301 THR second, third, sixth, ninth and twelfth months. patients, there were no statistically significant Plasma CRP levels were measured quan- differences in ESRs or CRP levels when 82 titatively by Behring® nephelometer (Behring patients with wound infections (six of which Marburg GmbH, Marburg, Germany) and ESR were deep infections) were compared with was determined by the Westergren method. those without wound problems.4 In another We calculated mean percentage changes study about a quarter of CRP levels and ESRs from the initial values for plasma CRP were normal before revision in 23 THR concentrations and ESR. Statistical comparisons patients in whom revisions were done because were done using the Wilcoxon test. of deep infection.8 After uncomplicated arthroplasty, the Results time taken for CRP levels and ESRs to reach The mean pre-operative CRP values in the their peaks, and then to return to normal THR and TKR groups were equal at 0.54 mg/dl levels seems to vary.1,2,6,10 – 13 In the present and the mean ESRs were 14.12 mm/h and study, we investigated the timing of the 16.08 mm/h, respectively. The highest mean changes in plasma CRP levels and ESRs in CRP values, 26.02 mg/dl in TKR patients and patients with uncomplicated arthroplasty. 23.17 mg/dl in THR patients, occurred on day Patients and methods 2 after operation (Fig. 1). Plasma CRP values decreased thereafter to means of 1.0 mg/dl in We studied 28 uncomplicated cases of THR patients (by day 21) and 0.88 mg/dl in primary osteoarthritis, 12 of whom the TKR group (at the end of the second underwent THR (43%) and 16 (57%) of month); these values did not differ whom underwent TKR between January significantly from the pre-operative values 1998 and May 1998. The THR group (P > 0.05). By the end of the third month the comprised eight women and four men with a mean plasma CRP values in both groups were mean age of 64 years and the TKR group, similar to the pre-operative values. There were four men and 12 women with a mean age of statistically significant differences between 61 years. For infection prophylaxis a 1500-mg the mean plasma CRP values in THR and TKR dose of cefuroxime was given intravenously patients on day 21 and at the end of the first before and two 750-mg doses were given month (P < 0.05). There were no other after the operation. For prophylaxis of deep statistically significant differences but mean venous thrombosis low-molecular-weight CRP values in TKR patients were also higher heparin (Dalteparine) 5000 IU was injected on days 1, 2, 3 and 7, and at the ends of the subcutaneously pre-operatively and then second and third months. These differences once daily for 2 weeks. Regional anaesthesia were slightly more marked when the changes was used in all cases. In the THR group non- were calculated as percentages of the pre- cemented prostheses were inserted using a operative value (data not shown). posterolateral approach but in TKR patients Mean ESRs were at their highest, 100.5 mm/h cemented prostheses were inserted using an and 101.3 mm/h in THR and TKR patients, anterior approach and a tourniquet. respectively, on post-operative day 5 (Fig. 2). 8 ÖF Bilgen, T Atıcı, K Durak et al. CRP values and ESRs after arthroplasty 30 25 20 Total knee replacement Total hip replacement 15 10 5 0 Start 1 2 3 4 5 6 7 21 1 2 3 6 9 12 Day Month Time after surgery FIGURE 1: Mean plasma C-reactive protein concentrations in patients who underwent total knee replacement () or total hip replacement (■) The ESRs decreased thereafter to means of Diagnosis of infection after arthroplasty is 25 mm/h at the end of the third month in THR quite difficult. Besides clinical, radiological patients and 25.6 mm/h in the ninth month in and scintillographic findings, laboratory TKR patients, values that did not differ determinations of plasma CRP levels and significantly from the pre-operative values (P > ESRs are valuable in the diagnosis of 0.05). The only significant difference between infection and in the selection of appropriate the ESRs of the THR and TKR groups was on treatment.3,16 – 18 The CRP level reacts more day 1 (P < 0.05). At the end of the twelfth rapidly and is more sensitive than is the month the ESRs in THR and TKR patients were ESR.2,5,7,9,11,19,20 Further, the use of cement and 21.3 and 22.1 mm/h, respectively, higher than tourniquets in operations does not appear to the pre-operative values. When the changes in affect CRP levels or ESRs.6,10,11,20,22 ESRs were calculated as percentages of the pre- Previous studies have reported that operative value, higher percentage variations plasma CRP levels in THR and TKR patients were found in the TKR group than in the THR increase rapidly after operation reaching group (Fig. 3). maximum values within 2 – 3 days, after which they decrease rapidly.1,6,10 – 12 Discussion In 186 patients undergoing uncomplicated Plasma levels of acute-phase proteins, such cemented THR and TKR, plasma CRP as CRP, synthesized by hepatocytes, and of reached a peak on day 2 after the operation fibrinogen, which has an effect on the whereas, in 87 patients undergoing acceleration of erythrocyte aggregation, uncemented THR and TKR, it reached its increase in response to tissue trauma in peak on day 3.6 Plasma CRP levels peaked on infection, inflammation and malignancy.14,15 day 3 in 109 THR patients, 97 of whom were 9 Plasma C-reactive protein concentration (mg/dl) ÖF Bilgen, T Atıcı, K Durak et al. CRP values and ESRs after arthroplasty 110 100 90 80 70 Total knee replacement 60 Total hip replacement 50 40 30 20 10 0 Start 1 2 3 4 5 6 7 21 1 2 3 6 9 12 Day Month Time after surgery FIGURE 2: Mean erythrocyte sedimentation rates in patients who underwent total knee replacement () or total hip replacement (■) 800 700 600 500 Total knee replacement 400 Total hip replacement 300 200 100 0 1 2 3 4 5 6 7 21 1 2 3 6 9 12 Day Month Time after surgery FIGURE 3: Mean percentage variations in erythrocyte sedimentation rates in patients who underwent total knee replacement () or total hip replacement (■) 10 % of pre-operative value Erythrocyte sedimentation rate (mm/h) ÖF Bilgen, T Atıcı, K Durak et al. CRP values and ESRs after arthroplasty given cemented and 12 uncemented THR, plasma CRP levels in the TKR and THR whereas in 39 patients undergoing groups occurred on day 21 and at the end of unicondylar knee replacement (UKR), the first month, but plasma CRP values were plasma CRP level peaked on day 2 after generally higher in TKR patients for the first operation.10 In our group of patients plasma 3 months after surgery; CRP levels had CRP levels reached their peak on day 2 after returned to pre-operative levels by day 21 in operation. Cemented or uncemented THR patients and by the end of the second application of prosthesis to a knee or hip month in TKR patients. These results suggest joint does not seem to influence the changes that in TKR patients, compared with THR in plasma CRP levels after operation (Fig. 1). patients, bone and bone marrow tissues were In arthroplasty patients, the time taken for subjected to more trauma, and that in TKR plasma CRP levels to return to normal after patients the degree of inflammation was surgery has been reported as 2,13 3,2,10,11 or higher and the duration longer. 6 – 81 weeks, whereas White et al.12 reported In many studies, in THR and TKR patients, that, at the first follow-up visit after discharge post-operative ESR has been reported to peak from hospital, the CRP levels had returned to on days 5 – 7 and to decline after day 7.2,5,10,11 normal, although the exact time-period was The present findings that the ESR reached its not reported. White et al.12 also reported that peak on day 5 after operation and began to the post-operative CRP level in TKR patients decrease from day 6 are consistent with was 50% more compared with that in THR earlier findings.5 The plasma CRP level patients until day 7 after operation; reached its peak more rapidly than did the thereafter the difference became statistically ESR, indicating that CRP levels are more insignificant and plasma CRP returned to responsive, a finding consistent with the normal levels at the same time in both literature.2,5,7,9,11,19,21 Statistically significant groups. Niskanen et al.6 also reported that the differences between ESRs on day 1 after timing of the return to normal plasma CRP surgery in our THR and TKR patients may levels was the same in TKR and THR patients, be attributable to haemodynamic changes and found higher plasma CRP levels in TKR resulting from plasma and blood patients than in THR patients. In our THR transfusions during THR operations, as and TKR patients, the 3 months that the mentioned in earlier reports.2,11 plasma CRP level took to reach its normal In our study, ESRs at the end of the third level was longer than the times previously month in THR patients and at the end of the reported but, as previously reported, the ninth month in TKR patients did not differ timing did not vary with technique. 6,12 In hip significantly from pre-operative values. This and knee arthroplasty, macrophages, which shows that ESR tends to decrease slowly are found in greater numbers in bone and compared with CRP, as reported in bone marrow than in muscle tissue, provide arthroplasty10 and in THR patients.22 The later an effective means of determining plasma decrease in ESR in TKR patients compared with CRP levels. The severity of bone and bone THR patients is likely to be for the reasons marrow trauma was also an influencing mentioned above in connection with the later factor. 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