Does intraoperative blood loss affect antibiotic serum and tissue concentrations?

Objective: To determine the effect of intraoperative blood loss on prophylactic cefazolin and gentamicin serum and tissue concentrations. Design: 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 underwent an elective surgical procedure that involved spinal instrumentation. Intervention: Standard perioperative administration of a combination of cefazolin and gentamicin. Serum and tissue samples were obtained consecutively throughout the surgical procedure. Main Outcome Measures: The effect of intraoperative blood loss on serum and tissue cefazolin and gentamicin concentrations and their pharmacokinetics. Results: At the time of the incision, serum cefazolin concentrations were greater than tissue concentrations (P=.07). A mean dose of 1.8-mg/kg gentamicin yielded low or nontherapeutic serum and tissue gentamicin concentrations. Cefazolin and gentamicin were eliminated from the tissue compartment slower than from the serum compartment (P<.03), while the half-life of cefazolin was significantly (P=.06) longer in the tissue compartment. The volume of distribution of cefazolin was normal (ie, 12.5 L), while the volume of distribution of gentamicin was 5-fold greater than expected. At 60 minutes after the incision, blood loss correlated with cefazolin tissue concentrations (r=- 0.66, P=.05). Blood loss correlated with the change in tissue antibiotic concentrations for cefazolin (r=0.73, P=.04). In addition, the clearance of gentamicin from the tissues correlated with blood loss (r=0.82, P=.01). Conclusions: Based on measured pharmacokinetic values, additional doses of cefazolin should be administered when the operation exceeds 3 hours and blood loss is greater than 1500 mL. Doses of gentamicin greater than 1.8 mg/kg should be administered more than 30 minutes prior to the surgical incision.