Low-dose IORA was effective in the high-BMI population group, providing tissue concentrations of vancomycin 6-8 times higher than systemic administration.
Obesity is an established risk factor for periprosthetic joint infection following total knee arthroplasty (TKA). In the obese patient, a larger dose of prophylactic antibiotic based on actual body weight is required to reach therapeutic concentrations. If vancomycin is used as the prophylactic agent, this requires a prolonged administration time, and carries a risk of systemic adverse effects including nephrotoxicity. Low-dose vancomycin via bolus intraosseous regional administration (IORA) mitigates these factors, and has been shown to obtain tissue concentrations 6-10 times greater than systemic administration in a non-obese population. IORA vancomycin also provided more effective prophylaxis against PJI in an animal model of TKA.
Enhancing prophylaxis is appealing in the higher-risk obese patient, but it is unclear how tissue concentrations are affected when IORA is used in this population. This study compared tissue concentrations of low-dose vancomycin via the IORA versus an actual body-weight adjusted systemic IV dose in primary TKA.
Twenty-two patients with a body mass index >35 undergoing TKA were randomized into two groups. The IV group received 15mg/kg (maximum of 2g) of systemic IV prophylactic vancomycin over a two hour infusion into an arm vein, timed to finish immediately prior to incision. The IORA Group received 500mg vancomycin in 150ml saline as a bolus injection into a tibial intraosseous cannula, below an inflated thigh tourniquet, immediately before skin incision.
Subcutaneous fat and bone samples were taken at regular intervals until skin closure. Tissue antibiotic concentrations were measured using high performance liquid chromatography. Blood sample was taken within one hour post-tourniquet deflation to measure systemic concentration.
The mean BMI was 41.1 (range 37-52) in the IORA group and 40.1 (range 35-52) in the IV systemic group. The overall mean tissue concentration in subcutaneous fat was 39.3ug/g in the IORA group and 4.4ug/g in the IV systemic group (p<0.01). Mean tissue concentrations in bone were 34.4ug/g in the IORA group and 6.1ug/g in the IV systemic group (p<0.01). Post-tourniquet deflation systemic concentration of vancomycin was 2.3mg/L in the intraosseous group and 16.6mg/L in the IV systemic group (p<0.01). Two patients in the IV systemic group developed superficial wound infections, no deep infections occurred in either group at time of follow up.
Low-dose IORA was effective in the high-BMI population group, providing tissue concentrations of vancomycin 6-8 times higher than systemic administration. This was despite an IORA unadjusted dose of 500mg, compared to a weight-adjusted systemic dose. Systemic concentrations remained low following tourniquet deflation in after IORA, and a higher IORA dose could be considered in the high BMI patient. IORA optimizes timing of vancomycin administration, and reduces the risk of systemic adverse effects, while providing high tissue antibiotic concentrations during TKA.