DOES INTRAOPERATIVE BLOOD-LOSS AFFECT ANTIBIOTIC SERUM AND TISSUE CONCENTRATIONS

Objective: To determine the effect of intraoperative blood loss on pro phylactic cefazolin and gentamicin serum and tissue concentrations. De sign: A prospective study of elective spinal instrumentation surgical procedures with an expected large blood loss. Setting: Tertiary care, inner-city university hospital. Patients: Eleven adult patients who un derwent an elective surgical procedure that involved spinal instrument ation. Intervention: Standard perioperative administration of a combin ation of cefazolin and gentamicin. Serum and tissue samples were obtai ned consecutively throughout the surgical procedure. Main Outcome Meas ures: The effect of intraoperative blood loss on serum and tissue cefa zolin and gentamicin concentrations and their pharmacokinetics. Result : At the time of the incision, serum cefazolin concentrations were gre ater than tissue concentrations (P=.07). A mean dose of 1.8-mg/kg gent amicin yielded low or nontherapeutic serum and tissue gentamicin conce ntrations. Cefazolin and gentamicin were eliminated from the tissue co mpartment slower than from the serum compartment (P<.03), while the ha lf-life of cefazolin was significantly (P=.06) longer in the tissue co mpartment. The volume of distribution of cefazolin was normal tie, 12. 5 L),while the volume of distribution of gentamicin was 5-fold greater than expected. At 60 minutes after the incision, blood loss correlate d with cefazolin tissue concentrations (r=-0.66, P=.05). Blood loss co rrelated with the change in tissue antibiotic concentrations for cefaz olin (r=0.73, P=.04). In addition, the clearance of gentamicin from th e tissues correlated with blood loss (r=0.82, P=.01). Conclusions: Bas ed on measured pharmacokinetic values, additional doses of cefazolin s hould be administered when the operation exceeds 3 hours and blood los s is greater than 1500 mt. Doses of gentamicin greater than 1.8 mg/kg should be administered more than 30 minutes prior to the surgical inci sion.