Should ESR and CRP be Included in the Routine Preoperative Workup for Primary Total Knee

Arthroplasty?Dale T. Landry Jr., MD

Vinod Dasa, MD

Disclosures• Dale T. Landry Jr., MD

– None

• Vinod Dasa, MD– Paid Consultant

• Bioventus• Myoscience

– Stock• Pacira

– Research Support• Cropper Medical• Department of Defense

Background• Periprosthetic Joint Infection (PJI)

– Most devastating complication of total joint arthroplasty– Most common reason for total knee arthroplasty 1

• 1% - 3% incidence with Primary Osteoarthritis 2-3

• 2% - 4% incidence with Rheumatoid Arthritis 4-5

• 3% - 7% incidence with Diabetes 6-7

– Cost of treatment of PJI over $50,000 per patient 8

– Overall yearly cost of greater than $300,000,000 2-3, 8

1. Bozic KJ, et.al. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2010;468:45-51.2. Phillips JE, et.al.. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone

Joint Surg Br. 2006;88:943-8.3. Della Valle CJ, et.al. PE. Periprosthetic sepsis. Clin Orthop Relat Res. 2004;420:26-31.4. Wilson, M. G.; et.al.. Infection as a complication of total knee-replacement arthroplasty. Risk factors and treatment in sixty-seven cases.

J. Bone and Joint Surg., 12-A: 878-883, July 19905. Poss, R.; et.al.. Factors influencing the incidence and outcome of infection following total joint arthroplasty. Clin. Orthop., 182:117-

126,1984.6. England, S. P.; et.al.. Total knee arthroplasty in diabetes mellitus. Clin. Orthop., 260: 130-134,1990.7. Papagelopoulos, P, et.al.. Long term outcome and survivorship analysis of primary total knee arthroplasty in patients with diabetes

mellitus. Clin. Orthop., 330:124-132,1996.8. Maderazo, E. G.; et.al. Late infections of total joint prostheses. A review and recommendations for prevention. Clin. Orthop., 229:131-

142,1988

Background

• Erythrocyte Sedimentation Rate (ESR) & C-Reactive Protein (CRP)• Simple, inexpensive, readily available, and accurate• Measures of the Acute Phase Reaction• Diagnosis of PJI• Treatment of PJI by following the trends

• ESR/CRP in combination are effective tools for helping diagnose PJI– Postop elevated levels of ESR/CRP are predictors of PJI 9-11

• Normal trends of ESR/CRP following THA/TKA are well-studied

9. Della Valle C, et.al.. Preoperative testing for sepsis before revision total knee arthroplasty. J Arthroplasty. 2007;22(6 Suppl. 2):90-3.10. Greidanus NV, et.al.. Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee

arthroplasty. A prospective evaluation. J Bone Joint Surg Am. 2007;89:1409-16.11. Parvizi J, et.al.. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res. 2008;466:2628-33..

Background• Erythrocyte Sedimentation Rate (ESR) 12-13

• Peaks on post-op day 5• Returns to normal at 7-9 months with TKA

• C-Reactive Protein (CRP) 14-15

• Peaks on post-op day 2• Returns to normal by 3-4 weeks with TKA • Remains WNL for aseptic loosening 16

• ESR/CRP nonspecific for PJI, and can be elevated in a number of other medical conditions 17

12. Park KK, et.al: Normative Temporal Values of CRP and ESR in Unilateral and Staged Bilateral TKA. Clin Orthop Relat Res. 2008 Jan;466(1):179-88. Epub 2008 Jan 3.

13. Bilgen O, et.al..: C-reactive protein values and erythrocyte sedimentation rates after total hip and total knee arthroplasty. J Int Med Res. 2001 Jan-Feb;29(1):7-12

14. Larsson S, et.al..: C-reactive protein (CRP) levels after elective orthopedic surgery. Clin Orthop Relat Res. 1992 Feb;(275):237-42.15. Niskanen, R. O, et.al., H.: Serum C-reactive protein levels after total hip and knee arthroplasty. J. Bone and Joint Surg., 78-B(3): 431-

433,1996.16. Shih, L.-Y., et.al.: Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip arthroplasty. Clin. Orthop.,

225:238-246,1987.17. Nielen M, et.al.. Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis. Arthritis &

Rheumatology. 2004; 50: 2423 – 2427

Background

• Sensitivity for PJI 18-19

• Elevated ESR .82• Elevated CRP .96• Excellent Negative Predictive Value when both are WNL

• Combination of ESR/CRP shown to be a cost-effective screening protocol for diagnosis of PJI 20

• Similar findings of the usefulness of combined ESR and CRP in the setting of PJI following TKA or THA have been reported 21-22

18. Spangehl MJ, et. al.. Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am. 1999 May;81(5):672-83

19. Greidanus NV, et. al.. Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty. A prospective evaluation. J Bone Joint Surg Am. 2007 Jul;89(7):1409-16.

20. Austin MS, et. al. .: A simple, cost-effective screening protocol to rule out periprosthetic infection. J Arthroplasty. 2008 Jan; 23(1):65-821. Bernard L, et. al.: Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature

review. Scand J Infect Dis. 2004;36(6-7):410-6.22. Schinsky M, Della Valle C. Perioperative testing for joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint Surg

Am. 2008; 90: 1869 – 1875.

Background• Normal Range of ESR 23-24

• Patient < 50 yrs– Males < 15 mm/hr– Females < 25 mm/hr

• Patient > 50 yrs– Males < 20 mm/hr– Females < 30mm/hr

• Normal Range of CRP 25

• CRP < 8.2mg/L

23. Caswell M. Effect of patient age on tests of the acute-phase response. Arch Pathol Lab Med 1993;117:906–90924. Bottinger LE, et. al. Normal erythrocyte sedimentation rate and age. Br Med J. 1967 Apr 8;2(5544):85-725. Shine B, et. al.. Solid-Phase Radioimmunoassays for C-reactive protein. Clin. Chim. Acta. 1981; 117:13–23.

Background• However, patients undergoing Total Knee Arthroplasty have other

comorbid medical conditions that may affect ESR/CRP– Urinary Tract Infection 26

– Rheumatoid Arthritis 27

– Hepatitis-C 28

– Crohn’s Disease 29

– Systemic Lupus Erythematosis 30

– Psoriasis 31

– Obesity 32

26. Rohrmann S, et. al. Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III). The Prostate. 2005; 62: 27 – 33.

27. Nielen M, et. al.. Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis. Arthritis & Rheumatology. 2004; 50: 2423 – 2427.

28. Salter M, et. al.. Correlates of Elevated Interleukin-6 and C-Reactive Protein in Persons With or at High Risk for HCV and HIV Infections. Journal of Acquired Immune Deficiency Syndromes. 2013; 24: 488 – 495.

29. Fagan E, et. al.. Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis. European Journal of Clinical Investigation. 1982; 12: 351 – 359.30. Borg E, et. al. C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: a prospective longitudinal study. The

Journal of Rheumatology. 1990; 17: 1642 – 164831. Stern, S. H.; et. al.. Total knee arthroplasty in patients with psoriasis. Clin. Orthop., 248:108-111,1989.32. Wilson, M. Get. Al.. Infection as a complication of total knee-replacement arthroplasty. Risk factors and treatment in sixty-seven cases. J. Bone and Joint

Surg., 12-A: 878-883, July 1990

Background

• Little data exists on interpretation of preoperative Elevated ESR/CRP

• No data exists on how to interpret postoperatively elevated ESR/CRP levels in the setting of preoperative elevation

Study Purpose

• Primary– Define the prevalence of preoperatively elevated ESR and CRP

within a cohort of healthy patients undergoing primary Total Knee Arthroplasty

• Secondary– Define any comorbidities that may contribute to preoperatively

elevated ESR and CRP

Materials & Methods• Retrospective chart review of patients who underwent Primary TKA

with one surgeon between October 2009 – May 2011• Demographics Including

– Age– Gender– BMI– Medical Comorbidities

• Pre-Op Lab Values Recorded– CRP– ESR– WBC

Materials & Methods• Overall Cohort Inclusion Criteria

– Total Knee Arthroplasty from October 2007 – May 2011– Pre-Op Labs Within 30 Days of Procedure

• WBC/ESR/CRP– At Least Six Months of Follow-Up– 94 Patients

• Idiopathic Cohort Exclusion Criteria– Previous Arthroplasty Performed– Pre-Op Infection/UTI– Chronic Inflammatory Process– 78 Patients

Results• Overall Cohort

• Elevated ESR – 41.5% (31/94)

• Elevated CRP – 28.7% (27/94)

• Idiopathic Cohort• Elevated ESR

– 38.5% (30/78)• Elevated CRP

– 26.9% (21/78)

Comparison of Overall Cohort and Idiopathic Cohort of Elevated ESR/CRP by Percent vs BMI (kg/m2)

• Patients with BMI of 18.5 – 24.9– 0% Elevated ESR– 0% Elevated CRP

• Patients with BMI of 25 – 29.9– 23.5% Elevated ESR– 11.8% Elevated CRP

• Patients with BMI of 30 – 39.9– 36 % Elevated ESR– 19.5% Elevated CRP

• Patients with BMI > 40– 64.7% Elevated ESR– 64.7% Elevated CRP

Comparison in Idiopathic Cohort of BMI Classification to Mean ESR and CRP

Conclusions

• Significant number of otherwise healthy patients undergoing TKA with idiopathically elevated ESR/CRP• Elevated ESR 38.5% • Elevated CRP 26.9%

• It is inappropriate to assume that an otherwise healthy patient has a normal ESR/CRP prior to undergoing primary joint arthroplasty

Conclusions• Direct correlation between BMI category and ESR/CRP

• Preoperatively, as patient’s BMI category increases, one should assume that their ESR/CRP levels are likely elevated– Patients with BMI of 18.5 – 24.9 kg/m2

» 0% Elevated ESR» 0% Elevated CRP

– Patients with BMI of 25 – 29.9 kg/m2

» 23.5% Elevated ESR» 11.8% Elevated CRP

– Patients with BMI of 30 – 39.9 kg/m2

» 36 % Elevated ESR» 19.5% Elevated CRP

– Patients with BMI > 40 kg/m2

» 64.7% Elevated ESR» 64.7% Elevated CRP

Conclusions

• As BMI category increases, so to does the mean of both elevated ESR/CRP as well as the mean of normal ESR/CRP• If periprosthetic infection is present, what threshold ESR/CRP

levels in different BMI classes should be used to determine infection clearance and timeliness of arthroplasty re-implantation?

• Suggests that large scale prospective studies should be performed to determine more accurate BMI category-specific normal reference ranges for ESR/CRP

Conclusions• Until the results of this study are validated or refuted with large scale

trials, one should consider attaining preoperative ESR/CRP values on all patients undergoing joint arthroplasty• Cheap & Readily available• May help put elevated post-op ESR/CRP values into perspective in

a patient with a painful arthroplasty– Do these elevated values represent true periprosthetic

infection?– Are these lab values being interpreted as elevated when in fact

they are WNL with respect to the patient’s BMI?

Acknowledgments

• Vinod Dasa, MD

• Louisiana State University Health Sciences Center• Department of Orthopaedic Surgery

• Ochsner Medical Center Kenner

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