Tourniquet inflation during total knee arthroplasty (TKA) is commonly used to reduce bleeding in the surgical field; thereby facilitating exposure and cementation. However, reducing circulation to the leg may also reduce antibiotic distribution to the peri-incisional tissues. Once inflated, further parenteral addition of antibiotics is not likely to achieve peak concentration. Some studies propose techniques of regional prophylaxis with a tourniquet to achieve higher cefazolin tissue concentrations. To our knowledge, the effect of tourniquet application on antibiotic tissue concentrations during total knee arthroplasty has not been explored. Furthermore, the effect of time from dose to incision, participants weight, and length of surgery on local tissue concentrations of Ancef are poorly understood. Considering that infections remain the leading source of early reoperation and revision surgery, insight and optimization of local tissue antibiotics is of paramount interest.

In Canada, over 130 000 cases of primary joint arthroplasty are performed annually, and this number is increasing steadily with the aging population. Projections from the United States estimate that, by 2030, more than 3.5 million primary joint arthroplasties will be performed annually. Although rare, with reported rates of 0.5-2% within 2 years, periprosthetic joint infection (PJI) is a devastating complication with serious morbidity. Effective use of antibiotic prophylaxis remains an important measure to prevent progression of an intraoperative contamination of the surgical site to an overt clinical infection. It creates a hostile environment in blood and tissue inhibiting pathogens that could contaminate the wound throughout the procedure. In order to be effective, the concentration of antibiotic must exceed the minimum inhibitory concentration (MIC) of the organism between skin incision and wound closure. S. aureus and Coagulase-negative staphylocci (CoNS), including S.epidermidis, cause close to half of deep infections and reported MIC ranges from 0.5 to 8 ug/ml in bone. Achieving fourfold MIC in tissue is recommended for halting the pathogen Cefazolin, efficient against most common pathogens in orthopaedics, has a good tissue penetration, minimal toxicity, low cost, and therefore is the antibiotic of choice in arthroplasty procedures. Pharmacokinetics studies have showed that Cefazolin achieves peak bone concentrations 40 minutes after parenteral application and based on systemic dosage methods, guidelines recommend that the antibiotic should be infused within 60 minutes before surgical incision. Compared to conventional systemic dosing, modern techniques using liquid chromatography and mass spectrometry can adequately measure antibiotic concentration in tissue like fat and bone.

Inclusion Criteria:

• Adults ages 18-85 who require a primary total knee replacement
• Any gender
• Osteoarthritis, rheumatoid arthritis, avascular necrosis

Exclusion Criteria:

• Severe allergy to antibiotic used in the study
• Severe renal dysfunction (eGFR < 30 ml/min)
• Methicillin-resistant Staphylococcus aureus (MRSA) colonization
• participants who require revision surgery