Clinical trial NCT01228825: Pharmacokinetics of Cefuroxime in Cardiac Surgery With Cardiopulmonary Bypass
Official title: Evaluation of Plasma Concentrations and Pharmacokinetics of Cefuroxime Administered Prophylactically in Patients Undergoing Coronary Surgery With Cardiopulmonary Bypass
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Surgery
Keywords: Cardiac surgery
Cardiopulmonary bypass
Antibiotic prophylaxis
Cefuroxime
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Santa Genoveva Hospital, Goiania GO, Brazil
First posted: 2010-10-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Twenty patients scheduled for coronary surgery were enrolled in the study.

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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the influence of CPB on plasma concentrations and pharmacokinetics of cefuroxime
timeFrame: 24 hours
Secondary outcomes:
measure: Assess whether the proposed dosing regimen is adequate to maintain plasmaconcentrations above (4 times the MIC).
timeFrame: 24 hours
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Heart Institute University of Sao Paulo
state: SP
Study officials:
affiliation: University of Sao Paulo
name: Fabiana AP Bosco Ferreira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sao Paulo
name: Maria Jose C Carmona, phD
role: STUDY_CHAIR
References: