Does intraoperative blood loss affect antibiotic serum and tissue concentrations?
S. M. Swoboda, C. Merz, J. Kostuik, B. Trentler and P. A. Lipsett
Department of Surgery, Johns Hopkins University Schools of Medicine and Nursing, Baltimore, Md., USA.
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.
