Pharmacokinetics of Cefuroxime in Cardiac Surgery With Cardiopulmonary Bypass
Condition: Cardiac Surgery
Study type: Observational

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
    

Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twenty patients scheduled for coronary surgery were enrolled in the study.
      
Biospecimen description: 
      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.
    
Keywords: Cardiac surgery; Cardiopulmonary bypass; Antibiotic prophylaxis; Cefuroxime