Pharmacokinetics of Cefazolin in Patients With Obesity Undergoing Surgery Requiring Cardiopulmonary Bypass

OBJECTIVE: The authors\u27 objective was to determine the adequacy of an institutional standard dosing practice for infection prophylaxis in open cardiac surgery in patients heavier than 120 kg undergoing cardiopulmonary bypass. DESIGN: A prospective, single-center, open-label study was used to determine if cefazolin serum concentrations were maintained above the minimum inhibitory concentration (MIC) throughout surgery. A pharmacokinetic model describing cefazolin disposition was developed for perioperative patients with morbid obesity, based on these values. Probability of target attainment was evaluated across the clinically relevant MIC spectrum. SETTING: Maine Medical Center is an academic hospital in Portland, Maine, affiliated with Tufts University School of Medicine. PARTICIPANTS: Twenty patients scheduled for cardiac surgery requiring cardiopulmonary bypass who weighed at least 120 kg. INTERVENTIONS: All patients received 2 g of cefazolin intravenously (IV) within 1 hour before incision, an additional 1 g injected into the cardiopulmonary bypass circuit at the initiation of bypass, and 2 g administered IV every 3 hours after the initial IV dose. MEASUREMENTS AND MAIN RESULTS: Cefazolin serum concentrations were collected after incision, after initiation of bypass, each hour of bypass, at the end of bypass, and at sternal closure. For patients weighing \u3e120 kg undergoing cardiac surgery, the studied dosing regimen met or exceeded targeted cefazolin concentrations for all study patients. The authors conducted probability of target attainment analyses using both 65% and 100% of time with unbound drug concentrations across clinically relevant MICs. CONCLUSION: The authors found that their current dosing strategy achieved a probability of target attainment \u3e90% throughout surgery for both total and unbound cefazolin concentrations, independent of cardiopulmonary bypass times