BACKGROUND: The diagnosis of joint replacement infection is a difficult clinical challenge that often occurs when the implant cannot be salvaged. We hypothesize that the pH value of synovial fluid could be an important indicator of the inflammatory status of the joint. However, in the literature, there is a lack of data on the pH changes in hip and knee joint replacements and their relation to infection and implant failure. In this study, we aimed to measure the pH levels of synovial fluid in patients with hip and knee joint replacements. We also investigated the potential of pH measurement as a diagnostic tool for joint replacement infection. In this study, we recorded the pH values to be 7.55 and 7.46 in patients where Pseudomonas aeruginosa was identified as the cause of the prosthetic joint infection. We attribute this to the different environments created by this specific bacterium. In other cases where the pH was higher, chronic mitigated infections were diagnosed, caused by strains of Staphylococcus aureus, Streptococcus agalactiase, and coagulase negative staphylococcus. MATERIALS AND METHODS: In our cohort of 155 patients with implanted hip (THA; n = 85) or knee (TKA; n = 70) joint replacements, we conducted a prospective study with a pH measurement. Out of the whole cohort, 44 patients had confirmed joint replacement infection (28.4%) (44/155). In 111 patients, infection was ruled out (71.6%) (111/155). Joint replacement infection was classified according to the criteria of the Musculoskeletal Infection Society (MSIS) from 2018. Based on the measured values, we determined the cut-off level for the probability of ongoing inflammation. We also determined the sensitivity and specificity of the measurement. RESULTS: The group of patients with infection (n = 44) had a significantly lower synovial fluid pH (pH = 6.98 ± 0.48) than the group of patients with no infection (n = 111, pH = 7.82 ± 0.29, p < 0.001). The corresponding median pH values were 7.08 for the patients with infection and 7.83 for the patients with no infection. When we determined the cut-off level of pH 7.4, the sensitivity level of infected replacements was 88.6%, and the specificity level of the measurement was 95.5%. The predictive value of a positive test was 88.6%, and the predictive value of a negative test was 95.5%. CONCLUSIONS: Our results confirm that it is appropriate to include a pH measurement in the diagnostic spectrum of hip and knee replacements. This diagnostic approach has the potential to provide continuous in vivo feedback, facilitated by specialized biosensors. The advantage of this method is the future incorporation of a pH-detecting sensor into intelligent knee and hip replacements that will assess pH levels over time. By integrating these biosensors into intelligent implants, the early detection of joint replacement infections could be achieved, enhancing proactive intervention strategies.

Department of Metals and Corrosion Engineering University of Chemistry and Technology Technická 5 166 28 Prague 6 Czech Republic

Department of Orthopaedics 1st Faculty of Medicine Charles University Prague and University Hospital in Motol 5 Úval 84 150 06 Prague 5 Czech Republic

Faculty of Mechanical Engineering Czech Technical University Technická 4 166 07 Prague 6 Czech Republic

Institute of Macromolecular Chemistry CAS Heyrovsého nám 2 162 00 Prague 6 Czech Republic

Zobrazit více v PubMed

Brause B.D. Microbes and antibiotics. In: Callaghan J.J., Rosenberg A.G., Rubash H.E., Simonian P.T., Wickiewicz T.L., editors. The Adult Knee. Lippincott Williams and Wilkins; Philadelphia, PA, USA: 2003.

Gallo J., Landor I., Vavrik P. Current Strategies for Prevention of Prosthetic Joint Infection. Acta Chir. Orthop. Traumatol. Cechoslov. 2006;73:229–236. doi: 10.55095/achot2006/033. PubMed DOI

Pulido L., Ghanem E., Joshi A., Purtill J.J., Parvizi J. Periprosthetic Joint Infection: The Incidence, Timing, and Predisposing Factors. Clin. Orthop. 2008;466:1710–1715. doi: 10.1007/s11999-008-0209-4. PubMed DOI PMC

Salvati E.A., Gonzalez D.V., Masri B.A., Duncan C.P. The infected total hip arthroplasty. Instr. CourseLect. 2003;52:223–245. PubMed

Douglas R.O., Elie F.B., Anthony R.B., Daniel L., Werner Z., James M.S., Nalini R., Arlen H., Walter R.W. Executive Summary: Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 2013;56:1–10. PubMed

Betsch B.Y., Eggli S., Siebenrock K.A., Täuber M.G., Mühlemann K. Treatment of Joint Prosthesis Infection in Accordance with Current Recommendations Improves Outcome. Clin. Infect. Dis. 2008;46:1221–1226. doi: 10.1086/529436. PubMed DOI

Jahoda D., Sosna A., Landor I., Vavrik P., Pokorny D., Hudec T. Double-period reimplantation using a spacer—The method of choice in the management of hip replacement infection. A comparison of methods used between 1979 and 1998. Acta Chir. Orthop. Traumatol. Cechoslov. 2003;70:17–24. PubMed

Ribeiro M., Monteiro F.J., Ferraz M.P. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques adjacent in studying bacterial-material interactions. Biomatter. 2012;2:176–194. doi: 10.4161/biom.22905. PubMed DOI PMC

McGarry S.A., Engemann J.J., Schmader K., Sexton D.J., Kaye K.S. Surgical-site infection due to Staphylococcus aureus among elderly patients: Mortality, duration of hospitalization, and cost. Infect. Control. Hosp. Epidemiol. 2004;25:461–467. doi: 10.1086/502422. PubMed DOI

Deirmengian C., Hallab N., Tarabishy A., Valle C.D., Jacobs J.J., Lonner J., Booth R.E. Synovial Fluid Biomarkers for Periprosthetic Infection. Clin. Orthop. Relat. Res. 2010;468:2017–2023. doi: 10.1007/s11999-010-1298-4. PubMed DOI PMC

Fink B., Makowiak C., Fuerst M., Berger I., Schäfer P., Frommelt L. The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements. J. Bone Jt. Surg. 2008;90:874–878. doi: 10.1302/0301-620X.90B7.20417. PubMed DOI

Birlutiu V. Diagnosis and management of orthopedic implant-associated infection: A comprehensive review of the literature. Biomed. Res. 2017;28:11

Trampuz A., Steckelberg J.M., Osmon D.R., Cockerill F.R., Hanssen A.D., Patel R. Advances in the laboratory diagnosis of prosthetic joint infection. Rev. Med. Microbiol. 2003;14:1. doi: 10.1097/00013542-200301000-00001. DOI

Lenski M., Scherer M.A. Diagnostic potential of inflammatory markers in septic arthritis and periprosthetic joint infections: A clinical study with 719 patients. Infect. Dis. 2015;47:399–409. doi: 10.3109/00365548.2015.1006674. PubMed DOI

Treuhaft P.S., McCarty D.J. Synovial fluid pH, lactate, oxygen and carbon dioxide partialpressure in various joint diseases. Arthritis Rheum. 1971;14:475–484. doi: 10.1002/art.1780140407. PubMed DOI

De Vecchi E., Romanò C.L., De Grandi R., Cappelletti L., Villa F., Drago L. Alphadefensin, leukocyte esterase, C-reactive protein, and leukocyte count in synovial fluid for pre-operative diagnosis of periprosthetic infection. Int. J. Immunopathol. Pharmacol. 2018;32:2058738418806072. doi: 10.1177/2058738418806072. PubMed DOI PMC

Parvizi J., Jacovides C., Adeli B., Jung K.A., Hozack W.J., Mark B. Coventry Award: Synovial C-reactive Protein: A Prospective Evaluation of a Molecular Marker for Periprosthetic Knee Joint Infection. Clin. Orthop. Relat. Res. 2012;470:54–60. doi: 10.1007/s11999-011-1991-y. PubMed DOI PMC

Lenski M., Scherer M.A. Synovial IL-6 AS Inflammatory Marker in Periprosthetic Joint Infections. J. Arthroplast. 2014;29:1105–1109. doi: 10.1016/j.arth.2014.01.014. PubMed DOI

Deirmengian C., Kardos K., Kilmartin P., Cameron A., Schiller K., Booth R.E., Parvizi J. The alpha-defensin test for periprosthetic joint infection out performs the leukocyte esterase test strip. Clin. Orthop. Relat. Res. 2015;473:198–203. doi: 10.1007/s11999-014-3722-7. PubMed DOI PMC

Frangiamore S.J., Gajewski N.D., Saleh A., Farias-Kovac M., Barsoum W.K., Higuera C.A. Alpha-defensin accuracy to diagnose periprosthetic joint infection—Best available test? J. Arthroplast. 2016;31:456–460. doi: 10.1016/j.arth.2015.09.035. PubMed DOI

Shahi A., Parvizi J. The role of biomarkers in the diagnosis of periprosthetic joint infection. EFORT Open Rev. 2017;1:275–278. doi: 10.1302/2058-5241.1.160019. PubMed DOI PMC

Menkin V., Warner C.R. Studies on inflammation. XIII. Carbohydrate metabolism, local acidosis and the cytological picture in inflammation. Am. J. Pathol. 1937;13:25–41. PubMed PMC

Parvizi J., Tan T.L., Goswami K., Higuera C., Della Valle C., Chen A.F., Shohat N. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J. Arthroplast. 2018;33:1309–1314. doi: 10.1016/j.arth.2018.02.078. PubMed DOI

Tomšík E., Gunar K., Kruncolva T., Ivanko I., Trousil J., Fojt J., Hybasek V., Daniel M., Sepitka J., Judl T., et al. Development of smart sensing film with nonbiofouling properties for potentiometric detection of local pH changes caused by bacterial and yeast infections around orthopedic implants. Adv. Mater. Interfaces. 2022;10:2201878. doi: 10.1002/admi.202201878. DOI

Harma K., Ivy M., Block D.R., Abdel M.P., Hanssen A.D., Beauchamp C., Perry K.I., Rosemark C.L., Greenwood-Quaintance K.E., Mandrekar J., et al. Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection. J. Orthop. Res. 2020;38:2664–2674. PubMed

Ropes I.W., Bauer W. Synovial Fluid Changes in Joint Disease. Harvard University Press; Cambridge, MA, USA: 1953.

Cummings N.A., Nordby G.L. Measurements of synovial fluid pH in normal and arthritic knees. Arthr Rheum. 1966;9:47–56. doi: 10.1002/art.1780090106. PubMed DOI

Gobelet C., Gerster J.C. Synovial fluid lactate levels in septic and non-septic arthritides. Ann. Rheum. Dis. 1984;43:742–745. doi: 10.1136/ard.43.5.742. PubMed DOI PMC

Thomas T.W., Roy T.S. Acidosis of synovial fluid correlates with synovial fluid leukocytosis. Am. J. Med. 1978;64:933–936. PubMed

Salar O., Phillips J., Porter R. Diagnosis of knee prosthetic joint infection; aspiration and biopsy. Knee. 2021;30:249–253. doi: 10.1016/j.knee.2020.12.023. PubMed DOI

Milošev I., Levašič V., Vidmar J., Kovač S., Trebše R. pH and metal concentration of synovial fluid of osteoarthritic joints and joints with metal replacements. J. Biomed. Mater. Res. Part B Appl. Biomater. 2017;105:2507–2515. doi: 10.1002/jbm.b.33793. PubMed DOI

Roman M., Fleaca R.S., Boicean A., Bratu D., Birlutiu V., RUS L.L., Cernusca M.S. Assessment of Synovial Fluid pH in Osteoarthritis of the Hip and Knee. Rev. Chim. 2017;68:1243. doi: 10.37358/RC.17.6.5649. DOI

Uthpala W., Sachindra K., John D.A., Caleb J.B., Jeffrey N.A. Synovial Fluid pH Sensor for Early Detection of Prosthetic Hip Infections. Adv. Funct. Mater. 2021;31:2104124. PubMed PMC

Iyengar K.P., Gowers B.T.V., Jain V.K., Ahluwalia R.S., Botchu R., Vaishya R. Smart sensor implant technology in total knee arthroplasty. J. Clin. Orthop. Trauma. 2021;22:101605. doi: 10.1016/j.jcot.2021.101605. PubMed DOI PMC