Plasma Cefazolin Levels During Cardiovascular Surgery: Effects of Cardiopulmonary Bypass and Profound Hypothermic Circulatory Arrest

Objectives: We sought to assess the effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on plasma cefazolin levels administered for antimicrobial prophylaxis in cardiovascular surgery.

Methods: Four groups (10 patients per group) were prospectively studied: vascular surgery without cardiopulmonary bypass (group A), cardiac surgery with a cardiopulmonary bypass time of less than 120 minutes (group B), cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes (group C), and cardiac surgery with cardiopulmonary bypass and profound hypothermic circulatory arrest (group D). Subjects received cefazolin at induction and a second dose before wound closure. Arterial blood samples were obtained preceding cefazolin administration, at skin incision, hourly during the operation, and before redosing. Cefazolin plasma concentrations were determined by using a radial diffusion assay, with Staphylococcus aureus as the indicator microorganism. Cefazolin plasma concentrations were considered noninhibitory at 8 mug/mL or less, intermediate at 16 mug/mL, and inhibitory at 32 mug/mL or greater.

Results: In group A cefazolin plasma concentrations remained greater than 16 mug/mL during the complete surgical procedure. In group B cefazolin plasma concentrations diminished to 16 mug/mL or less in 30% of the patients but remained greater than 8 mug/mL. In group C cefazolin plasma concentrations decreased to less than 16 mug/mL in 60% of patients and were less than 8 mug/mL in 50% of patients. In group D cefazolin plasma concentrations reached 16 mug/mL in 66% of the patients but decreased to 8 mug/mL in only 1 patient.

Conclusions: For patients undergoing cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes, a single dose of cefazolin before skin incision with redosing at wound closure does not provide targeted antimicrobial cefazolin plasma levels during the entire surgical procedure. Patients undergoing profound hypothermic circulatory arrest are better protected, but the described protocol of prophylaxis is not optimal.