Pharmacokinetics of Cefuroxime in Cardiac Surgery With Cardiopulmonary Bypass

Cardiac Surgery Clinical Trial

Official title:

Evaluation of Plasma Concentrations and Pharmacokinetics of Cefuroxime Administered Prophylactically in Patients Undergoing Coronary Surgery With Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01228825
• Other study ID #: SDC2760/06/005
• Status: Completed
• Phase: N/A
• First received: October 26, 2010
• Last updated: October 26, 2010
• Start date: May 2007
• Est. completion date: April 2008

Study information

• Verified date: October 2010
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Observational

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• patients scheduled for coronary surgery

Exclusion Criteria:

• 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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Cardiac Surgery

Locations

Country	Name	City	State
Brazil	Heart Institute University of Sao Paulo	Sao Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Santa Genoveva Hospital, Goiania GO, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Assess whether the proposed dosing regimen is adequate to maintain plasmaconcentrations above (4 times the MIC).	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.	24 hours	No