Effect of controlled hemorrhage on tissue and serum cefazolin clearance

Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.