title: Dosing antibiotic prophylaxis during cardiopulmonary bypass-a higher level of complexity? A structured review.
abstract: In highly invasive procedures such as open heart surgery, the risk of post-operative infection is particularly high due to exposure of the surgical field to multiple foreign devices. Adequate antibiotic prophylaxis is an essential intervention to minimise post-operative morbidity and mortality. However, there is a lack of clear understanding on the adequacy of traditional prophylactic dosing regimens, which are rarely supported by data. The aim of this structured review is to describe the relevant pharmacokinetic/pharmacodynamic (PK/PD) considerations for optimal antibiotic prophylaxis for major cardiac surgery including cardiopulmonary bypass (CPB). A structured review of the relevant published literature was performed and 45 relevant studies describing antibiotic pharmacokinetics in patients receiving extracorporeal CPB as part of major cardiac surgery were identified. Some of the studies suggested marked PK alterations in the peri-operative period with increases in volume of distribution (Vd) by up to 58% and altered drug clearances of up to 20%. Mechanisms proposed as causing the PK changes included haemodilution, hypothermia, retention of the antibiotic within the extracorporeal circuit, altered physiology related to a systemic inflammatory response, and maldistribution of blood flow. Of note, some studies reported no or minimal impact of the CPB procedure on antibiotic pharmacokinetics. Given the inconsistent data, ongoing research should focus on clarifying the influence of CPB procedure and related clinical covariates on the pharmacokinetics of different antibiotics during cardiac surgery. Traditional prophylactic dosing regimens may need to be re-assessed to ensure sufficient drug exposures that will minimise the risk of surgical site infections.
authors.affiliation: Faculty of Health Sciences, Department of Critical Care, University of Pretoria, Pretoria, South Africa.
authors.forename: Fathima
authors.initials: F
authors.lastname: Paruk
authors.affiliation: Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: f.sime@uq.edu.au.
authors.forename: Fekade B
authors.initials: FB
authors.lastname: Sime
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019072:Antibiotic Prophylaxis / Q000379:methods*; D002315:Cardiopulmonary Bypass; D006801:Humans; D011300:Preoperative Care / Q000379:methods*; D013530:Surgical Wound Infection / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Cardiac surgery; Extracorporeal therapy; Pharmacokinetics