Influence of cardiopulmonary bypass on cefuroxime plasma concentration and pharmacokinetics in patients undergoing coronary surgery.

OBJECTIVES The aims of this study were to evaluate the influence of cardiopulmonary bypass (CPB) on the plasma concentrations and pharmacokinetics of cefuroxime and to assess whether the cefuroxime dose regimen (a 1.5 g dose, followed by 750 mg every 6 h for 24 h) is adequate for cardiac surgery antibiotic prophylaxis. METHODS A prospective, controlled, observational study compared patients undergoing coronary surgery with CPB (CPB group, n = 10) or off-pump surgery (off-pump group, n = 9). After each cefuroxime dose, blood samples were sequentially collected and analysed using high-efficiency chromatography. For demographic data and pharmacokinetic parameters, the authors used Fisher's exact test for nominal variables and Student's t-test and the Mann-Whitney U-test for parametric and non-parametric variables, respectively. Plasma concentrations were compared using ANOVA, and the percentage of patients with a remaining plasma concentration of >16 mg/l within 6 h after each bolus was quantified in tabular form. RESULTS After each cefuroxime bolus was administered, both groups presented a significant decrease in plasma concentration over time (P < 0.001), without differences between the groups. The mean CPB time of 59.7 ± 21.1 min did not change cefuroxime plasma concentrations or pharmacokinetics. The mean clearance ± SD (ml/kg/min) and median elimination half-life (h) of the CPB group versus the off-pump group were 1.7 ± 0.7 versus 1.6 ± 0.6 (P = 0.67), respectively, and 2.2 versus 2.3 (P = 0.49), respectively. Up to 3 h following the first bolus of 1.5 g, but not after 6 h, all patients had plasma concentrations >16 mg/l (CPB group = 20% and off-pump group = 44%). However, after all 750 mg boluses were administered, concentrations <16 mg/dl were reached within 3 h. CONCLUSIONS CPB does not influence cefuroxime plasma concentrations. The dosing regimen is adequate for the intraoperative period, but in the immediate postoperative period, it requires further review.

[1]  P. Gastmeier,et al.  Sternal surgical site infection prevention - is there any room for improvement? , 2011, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[2]  Craig D. Miller,et al.  Vancomycin plasma concentrations in cardiac surgery with the use of profound hypothermic circulatory arrest. , 2010, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[3]  A. Haverich,et al.  Economic aspects of deep sternal wound infections. , 2010, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[4]  M. Carmona,et al.  Penetration of cefuroxime in subcutaneous tissue during coronary artery bypass grafting surgery. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[5]  J. Manďák,et al.  Tissue and plasma concentrations of antibiotic during cardiac surgery with cardiopulmonary bypass--microdialysis study. , 2008, Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia.

[6]  A. Michalopoulos,et al.  Cefuroxime as antibiotic prophylaxis in coronary artery bypass grafting surgery. , 2007, Interactive cardiovascular and thoracic surgery.

[7]  D. C. Miller,et al.  Plasma cefazolin levels during cardiovascular surgery: effects of cardiopulmonary bypass and profound hypothermic circulatory arrest. , 2006, The Journal of thoracic and cardiovascular surgery.

[8]  M. Carmona,et al.  Systemic availability of prophylactic cefuroxime in patients submitted to coronary artery bypass grafting with cardiopulmonary bypass. , 2005, The Journal of hospital infection.

[9]  D. Bratzler,et al.  Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  J. Ornato,et al.  ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). , 2004, Circulation.

[11]  D. Bratzler,et al.  Antimicrobial Prophylaxis for Surgery: An Advisory Statement from the National Surgical Infection Prevention Project , 2004 .

[12]  Y. Carmeli,et al.  Glycopeptides are no more effective than beta-lactam agents for prevention of surgical site infection after cardiac surgery: a meta-analysis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  K. Kent,et al.  Five-Year Follow-Up After Intracoronary Gamma Radiation Therapy for In-Stent Restenosis , 2004, Circulation.

[14]  M. Carmona,et al.  Micrométodo para quantificação de cefuroxima em plasma através da cromatografia líquida de alta eficiência: aplicação na profilaxia de pacientes submetidos à cirurgia cardíaca , 2003 .

[15]  M. Jacobs,et al.  Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters. , 2001, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[16]  B. Édouard,et al.  Comment: Converting Patients from Brand-Name Clozapine to Generic Clozapine , 2001, The Annals of pharmacotherapy.

[17]  D. Healy,et al.  Serum Concentrations of Cefuroxime after Continuous Infusion in Coronary Bypass Graft Patients , 2001, The Annals of pharmacotherapy.

[18]  B. Mets,et al.  The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass , 2000, Acta anaesthesiologica Scandinavica.

[19]  S. Hagl,et al.  The endogenous pathway is a major route for deep sternal wound infection. , 2000, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[20]  R. Pokela,et al.  Is single-dose antibiotic prophylaxis sufficient for coronary artery bypass surgery? An analysis of peri- and postoperative serum cefuroxime and vancomycin levels. , 1997, The Journal of hospital infection.

[21]  W. Bilker,et al.  Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations. , 1993, The Journal of thoracic and cardiovascular surgery.

[22]  B. Kreter,et al.  Antibiotic prophylaxis for cardiothoracic operations. Meta-analysis of thirty years of clinical trials. , 1992, The Journal of thoracic and cardiovascular surgery.

[23]  E. Mortier,et al.  Cardiopulmonary Bypass and the Pharmacokinetics of Drugs , 1989 .

[24]  M. Carmona,et al.  Perioperative cefuroxime pharmacokinetics in cardiac surgery. , 2007, Clinics.

[25]  P. Houck,et al.  The Society of Thoracic Surgeons Practice Guideline Series: Antibiotic Prophylaxis in Cardiac Surgery, Part I: Duration. , 2006, The Annals of thoracic surgery.

[26]  Timothy J Gardner,et al.  ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). , 2004, Circulation.

[27]  C. Kirkpatrick,et al.  Comment: serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients. , 2001, The Annals of pharmacotherapy.

[28]  W. Trick,et al.  Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. , 2000, The Journal of thoracic and cardiovascular surgery.

[29]  R. Larbuisson,et al.  Prophylaxis in cardiac surgery. A controlled randomized comparison between cefazolin and cefuroxime. , 1995, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[30]  E. Mortier,et al.  Cardiopulmonary bypass and the pharmacokinetics of drugs. An update. , 1989, Clinical pharmacokinetics.