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International Journal of Clinical Pharmacy

, Volume 37, Issue 4, pp 592–598 | Cite as

Targeting cefuroxime plasma concentrations during coronary artery bypass graft surgery with cardiopulmonary bypass

  • Marieke Aalbers
  • Peter G. J. ter Horst
  • Wobbe Hospes
  • Michel L. Hijmering
  • Alexander J. Spanjersberg
Research Article

Abstract

Backgound Patients are at risk for severe postoperative infections after coronary artery bypass graft (CABG) surgery. Clinical laboratory data showed that unbound plasma concentrations of cefuroxime were not always adequate, therefore we developed a new dosing regimen. Objective The aim of this prospective study is to evaluate the new dosing strategy by monitoring patients for unbound cefuroxime plasma concentrations during CABG surgery with cardiopulmonary bypass (CPB). Setting A Dutch teaching hospital. Methods In this prospective trial, patients scheduled for CABG surgery with CPB were included. A starting dose of 1500 mg cefuroxime was given with anesthesia induction, followed by 750 mg cefuroxime every hour until wound closure. In case of renal failure the dosing regimen was adapted. Serial blood samples were collected before, during and after the CPB process. Pharmacokinetic modelling was performed by using an ‘iterative two-stage Bayesian population procedure’. Main outcome measure Unbound plasma concentrations of cefuroxime. Results 22 patients were included, data could be evaluated of 21 patients. In 24 % of the patients the unbound cefuroxime plasma concentration was below the target range during surgery before CPB started. Patients with a bodyweight above 100 kg or age <60 years were more likely to have unbound plasma concentrations below the target range (P = 0.030 and P = 0.008). During CPB, the half-life of unbound cefuroxime increased by 17 % and the clearance decreased by 11 % compared to before CPB (P = 0.033 and P = 0.014). The mean pharmacokinetic parameters before, during and after CPB were as follows: elimination half-life 72, 84 and 76 min; clearance of unbound cefuroxime (Clu) 14.2, 12.7, 13.8 l/h and volume of distribution (Vu) 0.280, 0.284 and 0.290 l/kg respectively. Variations in unbound fractions before, during and after CPB were below 2 %, implicating the unbound fraction of cefuroxime is not influenced by CPB. Conclusion Our results show that CPB during CABG surgery does not lead to inadequate unbound cefuroxime concentrations. Age, renal function and possibly also weight are more important factors that can result in unbound plasma cefuroxime concentrations below the target value.

Keywords

Antibiotic prophylaxis Cardiopulmonary bypass Cefuroxime Coronary artery bypass graft surgery Pharmacokinetics 

Notes

Acknowledgments

The authors would like to thank the surgical and anaesthetic team at the Isala Klinieken for their support during the study.

Funding

The research was funded by the Isala Klinieken, Zwolle, The Netherlands.

Conflicts of interest

None.

Supplementary material

11096_2015_101_MOESM1_ESM.xls (150 kb)
Supplementary material 1 (XLS 150 kb)

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Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015

Authors and Affiliations

  • Marieke Aalbers
    • 1
  • Peter G. J. ter Horst
    • 2
  • Wobbe Hospes
    • 2
  • Michel L. Hijmering
    • 3
  • Alexander J. Spanjersberg
    • 3
  1. 1.Department of Clinical PharmacyHospital Pharmacy EmmenEmmenThe Netherlands
  2. 2.Department of Clinical PharmacyIsala ClinicsZwolleThe Netherlands
  3. 3.Department of Thoracic Anaesthesia and Intensive CareIsala ClinicsZwolleThe Netherlands

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