Intraoperative vancomycin pharmacokinetics in cardiac surgery with or without cardiopulmonary bypass.

BACKGROUND: Vancomycin is administered as antimicrobial prophylaxis to patients undergoing cardiac surgery, an intervention that usually requires cardiopulmonary bypass (CPB). Previous studies reported that CPB modifies vancomycin pharmacokinetic parameters. OBJECTIVE: To investigate intraoperative vancomycin pharmacokinetic changes in a large population of patients undergoing cardiac surgery with CPB (on-pump) and without CPB (off-pump). METHODS: In this prospective study, patients undergoing cardiac surgery received a single dose of vancomycin 1000 mg in a 60-minute intravenous infusion, with skin incision performed between 16 and 120 minutes after the end of the infusion. For the on-pump group, arterial samples were drawn before CPB (end of infusion, skin incision), during CPB (5, 30, and 60 minutes, and then every 60 minutes until CPB end), and after CPB (wound closure). For the off-pump group, arterial samples were drawn time-matched to the CPB period of the on-pump group. RESULTS: Two hundred thirty-six consecutive patients were enrolled: 215 in the on-pump group and 21 in the off-pump group. A total of 1682 serum vancomycin concentrations (median 7/patient) were measured. Vancomycin maximum concentration ([Cmax] on-pump, 45.6 mg/L; off-pump, 47.3 mg/L); area under the concentration-time curve, zero to 8 hours ([AUC0-8] on-pump, 104.6 mg*h/L; off-pump, 96.1 mg*h/L); volume of distribution ([Vd] on-pump, 31 L; off-pump, 28.2 L); and total body clearance ([Cl] on-pump, 6.23 L/h; off-pump, 7.05 L/h) were similar. Moreover, Cmax and AUC0-∞ (AUC, zero to infinity) showed values comparable to those found in previous studies performed on noncardiac surgery patients. CONCLUSIONS: In our study there were no significant differences in vancomycin Cmax, AUC0-8, Vd, and Cl between the on-pump and off-pump groups. CPB does not seem to significantly modify intraoperative vancomycin pharmacokinetics in patients undergoing cardiac surgery. The results of this study may contribute to increased knowledge of vancomycin pharmacokinetics.

Role of iron metabolism and oxidative damage in postmenopausal bone loss.

It has been suggested that iron-deficient rats have lower bone mass than iron-replete animals, but a clear association between bone and iron repletion has not been demonstrated in humans. A growing body of evidences also suggests a relation between lipid oxidation and bone metabolism and between iron metabolism and LDL oxidation. Iron availability to cells also depends on haptoglobin (Hp) phenotypes. Hp has also important antioxidant properties according to its phenotype, hence we evaluate whether Hp phenotype could influence bone density, iron metabolism and lipid oxidation. This cross-sectional study enrolled 455 postmenopausal women affected by osteoporosis (260) or not (195). Bone mineral density, markers of bone and iron metabolism, levels of oxidized LDL (oxLDL) and Hp phenotype were measured in all the subjects. Hp 1.1 and 2.2 frequency was higher and Hp 2.1 was lower in the patients with fragility fractures (80) compared with the controls. We therefore evaluate different Hp phenotypes as risk or protective factors against fragility fracture: Hp 2.1 is a protective factor against fracture while 1.1 is an important and 2.2 a moderate risk factor for fragility fractures. Lower serum iron was associated with elevated transferrin in patients with Hp 1.1; moreover patients had relative iron deficiency compared with the controls and fractured patients had higher level of oxLDL. We found that both iron metabolism and oxLDL varies according to Hp phenotypes and are predictive of bone density. Our data indicate that Hp 2.1 is a protective factor for fragility fractures, depending on its role on iron metabolism and its antioxidant properties.