November 1996

Does Intraoperative Blood Loss Affect Antibiotic Serum and Tissue Concentrations?

Author Affiliations

From the Department of Surgery, The Johns Hopkins University Schools of Medicine and Nursing (Ms Swoboda); the Departments of Pathology (Ms Merz) and Pharmacy (Mr Trentler), The John Hopkins Hospital; and the Departments of Orthopedics (Dr Kostuik) and Surgery (Dr Lipsett), The Johns Hopkins University School of Medicine, Baltimore, Md.

Arch Surg. 1996;131(11):1165-1172. doi:10.1001/archsurg.1996.01430230047009

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