Dosing antibiotic prophylaxis during cardiopulmonary bypass—a higher level of complexity? A structured review

Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

“…To establish an effective antimicrobial prophylaxis regimen with cefazolin for patients undergoing cardiothoracic surgery with CPB, we should develop a pharmacokinetic model that describes the disposition of plasma unbound drug during operation. The pharmacokinetics of plasma unbound cefazolin during CPB may be influenced by complex physiological changes associated with the procedure (including low serum albumin levels, transient increase in volume of distribution by connecting the CPB circuit to systemic circulation, changes in circulating volume by infusion and blood loss, and changes in liver and kidney perfusion) . The disposition of cefazolin may be particularly susceptible to alteration associated with CPB‐induced physiological changes, since the drug has a small volume of distribution (0.19 L kg −1 or 11.4 L per 60 kg) and binds extensively to albumin (80%‐86%) .…”

“…As a result, consensus has not been attained about the choice and dosing protocols of antibiotics for these patients. 5 The guidelines of the American Society of Health-System Pharmacists recommend that traditional antimicrobial prophylaxis protocols for general surgery should not be changed for patients undergoing cardiothoracic surgery with CPB, unless further clinical outcome data obtained from well-designed studies are available. 1 Nevertheless, recent studies argued that conventional regimens of cefazolin prophylaxis for these patients may not be reliable in maintaining a target plasma threshold (for example, total drug concentration of 40 μg mL −1 , assuming normal protein binding of 80%-86% 6,7 during CPB) at intraoperative trough and/or at wound closure in patients with normal renal function undergoing cardiac surgery with CPB.…”

“…While cardiothoracic surgery is often performed with cardiopulmonary bypass (CPB), there is a paucity of knowledge about changes that may occur in the pharmacokinetics of drugs during CPB. As a result, consensus has not been attained about the choice and dosing protocols of antibiotics for these patients . The guidelines of the American Society of Health‐System Pharmacists recommend that traditional antimicrobial prophylaxis protocols for general surgery should not be changed for patients undergoing cardiothoracic surgery with CPB, unless further clinical outcome data obtained from well‐designed studies are available .…”

Population pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis during and after cardiopulmonary bypass

“…PAP in cardiac surgery with use of cardiopulmonary bypass (CPB) differs from other settings in which prophylactic antibiotics are used. The connection of the patient to the CPB‐circuit goes along with numerous physiological alterations, 14 affecting distribution of antibiotics. Additionally, antibiotic concentrations can be reduced by intraoperative bleeding and substitution of blood loss.…”

Antimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound Infections

“…AP is particularly beneficial in cardiac surgery, where serious and potentially lifethreatening infections, such as mediastinitis, can be prevented (1,2,9). In this population, AP must also account for complex and prolonged procedures, as well as for altered pharmacokinetics with cardiopulmonary bypass (CPB) (10). In the absence of defined targets, there are various approaches that adjust AP for cardiac surgery by using higher doses, more frequent redosing, or continuous infusions (11).…”