THE INFLUENCE OF DIFFERENT METHODS OF AUT OLOGOUS BLOOD-TRANSFUSION ON PLASMA-LEVELS OF ANTIBIOTICS - STUDY OF THE CEPHALOSPORINE CEFAMANDOLE

Infection after open heart surgery is a serious complication since era dication of infection in these cases is difficult even with appropriat e antibiotic therapy. In the attempt to avoid this problem, prophylact ic administration of antibiotics is common. Their relative safety and their broad spectrum of activity make cephalosporin antibiotics popula r choices for prophylaxis prior to and during operations, including ca rdiovascular procedures. Methods. Preoperative antibiotic prophylaxis with 2 g cefamandole was performed in a prospective randomized study i ncluding 62 male patients divided into three groups. All patients gave informed consent, and the study was approved by the ethics committee of the hospital. Patients in group 1 (n = 21) and group 2 (n = 21) und erwent aortocoronary bypass (ACVB) with extracorporeal circulation (EC C), while patients in group 3 (n = 20) had carotid surgery. Anaesthesi a, coronary-bypass procedures and infusion regime were standardized. T he flow rate during ECC was maintained at 2.4 l/min/m2 and the rectal temperature between 33-degrees and 34-degrees-C. Arterial and urine sp ecimens for the determination of plasma and urine levels of cefamandol e were taken at definite times. Autologous blood salvage during operat ion was performed with haemofiltration techniques (HF) in group 1 (HF 80, Fresenius, Bad Homburg, Germany) and with cell separation techniqu es (CS) in group 2 (Hemonetics III, Hemonetics). Plasma and urine cefa mandole levels were measured by high-pressure liquid chromatography (H PLC). Results. After administration of 2 g cefamandole mean peak level s of 404.6 +/- 141.7 mug/ml were seen. Because of haemodilution at the beginning of extracorporeal circulation, group 1 and 2 showed much lo wer cefamandole plasma levels, 22.1 +/- 11.6 mug/ml and 24.3 +/- 14.4 mug/ml, than group 3 (after the same time course), with 47.4 +/- 19.1 mug/ml. For all patients in group 1 and 2 prebypass time (70.3 +/- 22. 4 min) and the duration of the ECC (72.3 +/- 17.7 min) were comparable . There was a significant correlation between prebypass time and cefam andole plasma levels at the beginning of extracorporeal circulation (P < 0.001). No correlation could be seen for the plasma concentration a fter discontinuation of the extracorporeal circulation and the duratio n of extracorporeal circulation. The volume of autologous red packed c ells and the enclosed amount of cefamandole showed a significant diffe rence (P < 0.001) between group 1 (1120.0 +/- 296.8 ml, 27.5 +/- 17.1 mg) and group 2 (734.3 +/- 186.6 ml, 2.9 +/- 3.2 mg). The plasma cefam andole level after transfusion of autologous blood displayed a signifi cant correlation (P < 0.01) with cefamandole concentration in the auto logous red packed cells. Transfusion of the autologous blood produced no significant increase in plasma cefamandole levels. With an operatio n time of more than 2.5 h during ECC the cefamandole plasma level decr eased below the necessary minimal inhibitory concentration (MIC90), pa rticularly for gram-negative bacteria. Conclusion. Additional administ ration of 1 g cefamandole shortly before the beginning of cardiopulmon ary bypass is recommended, particularly for surgical procedures with E CC of more than 2.5 h. Adjustment of drug dosage prior to or during su rgery may be required to optimize therapy, but before this can be achi eved precisely, more information on drug disposition during the operat ive procedures is needed.