EFFECT OF TOURNIQUET ON LOCAL TISSUE CONCENTRATIONS OF CEFAZOLIN DURING TOTAL KNEE ARTHROPLASTY: A RANDOMIZED CLINICAL TRIAL

Prophylactic administration of intravenous antibiotics prior to skin incision is arguably the most important measure to prevent periprosthetic joint infection (PJI) in arthroplasty surgery. To be effective, the local tissue concentration (LTC) of antibiotic must exceed the minimum inhibitory concentration (MIC) of typical infecting organisms. However, the LTC of Cefazolin during arthroplasty surgeries remains poorly understood. Our aim was to compare the systemic concentration of Cefazolin in serum with the LTC in fat, synovium and bone during primary total knee arthroplasty (TKA) while assessing the impact of tourniquet inflation. A prospective randomized clinical trial conducted from March 2022 June 2023 at a single Canadian academic center. Sixty-one consecutive patients undergoing primary TKA were randomized, and 59 patients were included in the analysis. Patients were randomized to TKA surgery perfromed with or without a limb tourniquet. Systemic blood and local tissues from the surgical site (fat, synovium and bone) were harvested at regular intervals during the surgery. The concentration of Cefazolin was quantified using a liquid chromatography–tandem mass spectrometry (LC-MS) technique. In patients undergoing TKA without a tourniquet, the mean concentration of Cefazolin in the serum was 71.9 ug/ml (SD 32.7) whereas the LTC in fat, synovium, and bone was 13.9 ug/g (8.6), 27.7 ug/g (12.6) and 17.7 ug/g (9.9), respectively. For patients undergoing TKA with a tourniquet, the mean concentration of Cefazolin in serum was 72.0 ug/ml (SD 32.6), while the LTC in fat, synovium, and bone was 9.9 ug/g (5.7), 21.8 ug/g (11.3) and 13.0 ug/g (7.7) respectively. The use of a tourniquet resulted in significantly lower LTCs in fat, synovium and bone by 60 minutes after cefazolin infusion (Fat p=0.001, Synovium p=0.03, Bone=0.007). The concentration of Cefazolin was found to be much lower in local tissues (fat, synovium and bone) than in systemic blood and the use of a limb tourniquet further significantly reduced these concentrations. Although the current prophylactic dosing regimen for Cefazolin provides sufficient serum concentrations, the levels in the local periarticular tissue during TKA may be insufficient to prevent PJI.