Pharmacokinetics of Cefuroxime in Cardiac Surgery With Cardiopulmonary Bypass
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|ClinicalTrials.gov Identifier: NCT01228825|
Recruitment Status : Completed
First Posted : October 27, 2010
Last Update Posted : October 27, 2010
|Condition or disease|
In cardiac surgery, the use of cardiopulmonary bypass may alter the kinetics and plasma concentration of drugs, including antibiotics. On the other hand, infection of the surgical field and/or mediastinitis are serious complications of cardiac surgery, with incidence ranging from 1.9 to 15%, especially when considering the lower limb infections. Inadequate prophylactic antibiotic therapy, besides not preventing infection, it can select resistant microorganisms. The second-generation of cephalosporin antibiotics have been the most used as prophylactic antibiotic for cardiac surgery due to its low toxicity and cost, good tissue penetration, good spectrum of activity against bacterias that often cause postoperative infection, i.e. Staphylococcus aureus and coagulase negative Staphylococcus, which colonize the patients' skin, and Escherichia coli, Klebsiella spp, Enterobacter spp, Proteus spp, and Pseudomonas spp, bacteria common in the lower limb or perineum which may contaminate the chest or the location of the saphenectomy. Regarding cefuroxime, it is important that the plasma concentration four times higher than the MIC (minimal inhibitory concentration), i.e. 16 g/L is maintained throughout the surgical procedure.
However, there is no consensus on the ideal dosage to be used to maintain this concentration for prevention of infection in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Nascimento et al. demonstrated that, in patients undergoing coronary artery bypass graft (CABG) with CPB, the cefuroxime in a dose of 1.5 g every 12 hours, for 24 hours showed plasma concentrations below antibiotic prophylaxis with 16 g/L MIC after the ninth hour.
After these results, the institutional dosing changed to 1.5 g bolus at induction of anaesthesia, followed by a bolus of 750 mg every 6 hours, for 24 hours. It is necessary a study to test this dosing regimen and the influence of CPB on plasma concentrations and pharmacokinetics of cefuroxime
|Study Type :||Observational|
|Actual Enrollment :||19 participants|
|Official Title:||Evaluation of Plasma Concentrations and Pharmacokinetics of Cefuroxime Administered Prophylactically in Patients Undergoing Coronary Surgery With Cardiopulmonary Bypass|
|Study Start Date :||May 2007|
|Actual Primary Completion Date :||April 2008|
|Actual Study Completion Date :||April 2008|
CABG without CPB
Patients undergoing coronary artery bypass graft (CABG) without Cardiopulmonary bypass ( CPB)
CABG with CPB
Patients undergoing coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB)
- Evaluate the influence of CPB on plasma concentrations and pharmacokinetics of cefuroxime [ Time Frame: 24 hours ]Some authors argue that CPB could trigger a drop in the drug plasma concentration due to hemodilution, changes in volume of distribution, redistribution of blood flow to peripheral tissue, vasodilatation due to inflammatory, drug sequestration by the CPB circuit and/or the lungs. Others argue the pharmacokinetics of water-soluble cephalosporin showed that the rate of elimination is dependent on renal function, with reduction of plasma clearance, prolongation of biological half-life, and elevated plasma concentrations at the end of CPB.
- Assess whether the proposed dosing regimen is adequate to maintain plasmaconcentrations above (4 times the MIC). [ Time Frame: 24 hours ]Nascimento et al. (2005) demonstrated that, in patients undergoing coronary artery bypass graft (CABG) with CPB, antibiotic prophylaxis with cefuroxime in a dose of 1.5 g every 12 hours, for 24 hours showed plasma concentrations below MIC (16 g/L) after the ninth hour. After these results, the institutional dosing changed to 1.5 g bolus at induction of anaesthesia, followed by a bolus of 750 mg every 6 hours, for 24 hours.
Biospecimen Retention: Samples With DNA
Blood samples were collected sequentially after the administration of initial bolus of cefuroxime every 15 minutes during the first hour, then within two, three and six hours.
Samples were also collected every 15 minutes during CPB. Group Off-Pump had equivalent collections, considering the time after heparinization and anastomosis initiation. Four other blood samples were collected at times considered as high risk for bacterial contamination, i.e.
chest incision, beginning of anastomosis, after protamine administration, and chest suture.
After each bolus of 750 mg, samples were collected within 30 minutes, one, three, and six hours.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01228825
|Heart Institute University of Sao Paulo|
|Sao Paulo, SP, Brazil, 05403000|
|Principal Investigator:||Fabiana AP Bosco Ferreira, MD||University of Sao Paulo|
|Study Chair:||Maria Jose C Carmona, phD||University of Sao Paulo|