OBJECTIVE: Cardiopulmonary bypass (CPB) alters the pharmacokinetics (PK) of antibiotics administered as surgical prophylaxis (SAP) due to haemodilution, circuit interactions, protein binding and inflammation. This study investigated plasma and interstitial fluid (ISF) concentrations of cefuroxime in patients undergoing on- versus off-pump coronary artery bypass graft (CABG) surgery. METHODS: Patients undergoing on- or off-pump CABG received SAP with cefuroxime, consisting of a bolus of 3 g before skin incision and a second dose of 1.5 g at CPB weaning or at sternal closure, respectively. ISF concentrations were measured by two microdialysis catheters in the subcutaneous tissue of both upper arms. Plasma and ISF concentrations were determined up to 8 hours after the first dose. Pharmacokinetic analysis was performed by non-compartmental analysis. RESULTS: Fifteen patients were enrolled per group. Baseline characteristics and cardiovascular risk profile were comparable between groups. Median minimum; maximum surgical duration was 4.3 h 3.1 h; 6.1 h in the on-pump and 3.4 h 1.8 h; 4.0 h in the off-pump group, with a median bypass time of 1.7 h 0.8 h; 2.5 h. The ƒAUC0-8h in plasma (on-pump versus off-pump group; mean ± SD: 417 ± 124 versus 542 ± 238 h·mg/L, P = 0.081) and in ISF (488 ± 212 versus 508 ± 209 h·mg/L, P = 0.835) did not differ significantly. Based on an extrapolation of the first dose, plasma concentrations remained above a minimum inhibitory concentration of 8 mg/L for up to 4.5 h in the on-pump and 4.8 h in the off-pump group. CONCLUSION: For a median bypass time of 1.7 h and considering all factors cumulatively, no significant impact of CPB on cefuroxime plasma and ISF concentrations was observed. A dose of 3 g cefuroxime administered intravenously 30-60 min before skin incision with a second repetitive dose of 1.5 g administered after CPB weaning in the on-pump group or after sternal closure in the off-pump group, resulted in adequate plasma and ISF concentrations in patients undergoing cardiac bypass surgery.
Nothofer et al. (Fri,) studied this question.