Pharmacokinetics of Cefuroxime in Cardiac Surgery With Cardiopulmonary Bypass

NCT01228825 | Completed

• 1 other identifier: SDC2760/06/005
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Infection, especially mediastinitis, is major complication in cardiac surgery. Considering that cardiopulmonary bypass (CPB) can alter kinetics of drugs, including antibiotics, the aim of this study was to evaluate the influence of cardiopulmonary bypass ( CPB) on plasma concentrations and pharmacokinetics of cefuroxime, administered prophylactically, in a 1.5g dose, followed by three bolus of 750mg every 6 hours, for 24 hours, in 19 patients undergoing coronary artery bypass graft (CABG) with CPB (CPB Group, n = 10), or without CPB (Off-Pump Group, n = 9); and assess whether the proposed dosing regimen is adequate to maintain plasma concentrations above 16 g/L (4 times the MIC) for the first 24 hours after the beginning of surgery.

Conditions

Cardiac Surgery

Keywords

Cardiac surgery; Cardiopulmonary bypass; Antibiotic prophylaxis; Cefuroxime

Outcome Measures

Primary Outcomes (1)

• Evaluate the influence of CPB on plasma concentrations and pharmacokinetics of cefuroxime

  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.

  24 hours

Secondary Outcomes (1)

• Assess whether the proposed dosing regimen is adequate to maintain plasmaconcentrations above (4 times the MIC).

  24 hours

Study Arms (2)

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)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Twenty patients scheduled for coronary surgery were enrolled in the study.

You may qualify if:

• patients scheduled for coronary surgery

You may not qualify if:

• Patients over 75 years old,
• body mass index (BMI) over 35 kg/m2,
• left ventricle ejection fraction below 35%,
• serum creatinine greater than or equal to 1.4 mg/dL,
• prothrombin activity lower than 80%,
• serology positive for hepatitis,
• use of oral anticoagulants,
• allergy to cefuroxime

Sponsors & Collaborators

• University of Sao Paulo: lead
• Santa Genoveva Hospital, Goiania GO, Brazil: collaborator

Study Sites (1)

Heart Institute University of Sao Paulo

São Paulo, São Paulo, 05403000, Brazil

Location

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.

Study Officials

• Fabiana AP Bosco Ferreira, MD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

• Maria Jose C Carmona, phD

  University of Sao Paulo

  STUDY CHAIR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 26, 2010
• First Posted: October 27, 2010
• Study Start: May 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: October 27, 2010

Record last verified: 2010-10

Locations

BR (1)