Higher tissue concentrations of cefuroxime achieved with preoperative stand-alone intraosseous regional prophylaxis in robotic-assisted total knee arthroplasty: a randomized controlled trial

Abstract Background Intraosseous regional administration (IORA) of antibiotics can achieve higher local tissue concentrations than intravenous administration in conventional total knee arthroplasty (TKA). This study aimed to evaluate the tissue concentration and systemic concentration of preoperative stand-alone intraosseous cefuroxime in robotic-assisted total knee arthroplasty (RA-TKA) and identify a candidate dose for further evaluation. Methods Thirty-nine patients undergoing MAKO RA-TKA were randomly allocated in a 1:1:1 ratio to receive intraosseous cefuroxime 750 mg (R750 IO ), intraosseous cefuroxime 1,500 mg (R1500 IO ), or intravenous cefuroxime 1,500 mg (R1500 IV ). No additional intravenous antibiotics were administered before incision or during surgery. During surgery, nine tissue samples were collected: bone samples from the femur or tibia, synovial and fat samples from the surgical area, and systemic blood samples twice for cefuroxime level detection. Intraoperative vital signs, inflammatory markers on days 1 and 3 postoperative, and complications within 3 months were recorded. Results The final analysis included 38 patients: 13 in the R750 IO group, 13 in the R1500 IO group, and 12 in the R1500 IV group. Compared with the R1500 IV group, both R1500 IO and R750 IO groups showed significantly higher tissue concentrations ( p < 0.05) but lower initial blood concentrations ( p < 0.05). While the R1500 IO group had higher tissue concentrations than the R750 IO group, its post-tourniquet-release blood concentration was significantly higher ( p = 0.005). No significant differences were found in postoperative inflammatory markers and intraoperative vital signs among the three groups ( p > 0.05), and no complications occurred within 3 months. Conclusions Despite multiple intramedullary pins and longer operative time in robot-assisted TKA, a single intraosseous dose of cefuroxime still achieved high tissue concentrations. Compared to conventional intravenous infusion of 1,500 mg cefuroxime, preoperative stand-alone intraosseous administration of either 750 mg or 1,500 mg cefuroxime achieved higher local tissue concentrations. Moreover, the 750 mg intraosseous regimen was associated with a lower post-tourniquet-release systemic concentration than the 1,500 mg intraosseous regimen, supporting its further clinical evaluation as a candidate dose in RA-TKA.