Tissue and plasma concentrations of cephuroxime during cardiac surgery in cardiopulmonary bypass--a microdialysis study.
OBJECTIVE
Wound and mediastinal infections are still very serious complications of open-heart surgery, in spite of the use of prophylactic antibiotics. The use of cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting the pharmacokinetic behaviour of antibiotics. The aim of this pilot study was to monitor the tissue concentrations of cephuroxime (prophylactic antibiotic) in skeletal muscle during cardiac surgery using CPB by interstitial microdialysis. These concentrations were compared with plasma concentrations of cephuroxime.


METHODS
Nine adult patients operated on using CPB were enrolled in this study. Cephuroxime was used as a prophylactic antibiotic (1st dose - 3 g of cefuroxime i.v. with anesthesia induction, 2nd dose - 1.5 g i.v. after CPB with protamine sulphate, 3rd dose - 1.5 g i.v. 8 hours after the surgery). Interstitial microdialysis was performed by probe CMA 60 (CMA Microdialysis AB, Sweden) inserted into the patient's deltoid muscle. Concentrations of cephuroxime in dialysates and in plasma were determined by the modified fluid chromatography method. The unbound cephuroxime fraction in plasma was obtained by using an ultrafiltration method. Samples of dialysates were collected at the following intervals: before CPB, each 30 minutes of CPB, at the end of CPB. Samples of blood were collected at these intervals: incision, start of CPB, each 30 minutes of CPB, at the end of CPB, at the end of surgery. Concentrations of cephuroxime in tissue were corrected by in vivo recoveries of the microdialysis probes.


RESULTS
Plasma concentrations of cephuroxime were 163.5 +/- 40.1, 79.3 +/- 17.4, 73.7 +/- 16.8, 66.1 +/- 18.3, 57.0 +/- 10.9, 120.7 +/- 29.9 (mg L(-1)) and concentrations of free plasma fraction of cephuroxime were 119.5 +/- 35.2, 67.8 +/- 15.5, 66.0 +/- 12.5, 54.8 +/- 12.2, 49.6 +/- 9.8, 102.6 +/-26.0 (mg L(-1)). The concentrations of cephuroxime in dialysates were 44.3 +/- 15.7, 36.1 +/- 11.6, 31.9 +/- 9.3, 34.6 +/- 12.3, 27.6 +/-12.9, 56.7 +/- 17.6 (mg L(-1)). The mean in vivo recovery of cephuroxime in this study was 30%. Corrected concentrations (calculated by in vivo recovery) of cephuroxime in skeletal muscle were 148, 120, 106, 115, 92, 189 (mg L(-l)).


CONCLUSIONS
Our preliminary results show that CPB can modify the time course of cephuroxime plasma and tissue concentrations. A decrease in plasma drug concentrations occurred at the start of CPB and lasted until CPB ended. An increase in plasma concentrations corresponds to the second drug dose after CPB. The concentrations of cephuroxime in skeletal muscle (corrected by recovery) during CPB are higher than plasma concentrations. It is influenced by important changes during CPB; closely associated with hemodilution, a shift of intravascular volume, solutes and albumin to the extravascular space and inconstant protein binding of cephuroxime during operation.
Mand'ák
J
J
Department of Cardiac Surgery, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic. jiri.mandak@centrum.cz
Pojar
M
M
Maláková
J
J
Lonsk
V
V
Palicka
V
V
Zivný
P
P
D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass; D002444:Cefuroxime / Q000097:blood* / Q000493:pharmacokinetics*; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D007552:Isotonic Solutions; D017551:Microdialysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010865:Pilot Projects; D000077331:Ringer's Solution; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D007552:Isotonic Solutions; D000077331:Ringer's Solution; D002444:Cefuroxime