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.
Arch Surg. 1996;131:1165-1172
