[The effect of different autotransfusion procedures on the antibiotic picture. A study on cephalosporin cefamandole].

Infection after open heart surgery is a serious complication since eradication of infection in these cases is difficult even with appropriate antibiotic therapy. In the attempt to avoid this problem, prophylactic administration of antibiotics is common. Their relative safety and their broad spectrum of activity make cephalosporin antibiotics popular choices for prophylaxis prior to and during operations, including cardiovascular procedures. METHODS. Preoperative antibiotic prophylaxis with 2 g cefamandole was performed in a prospective randomized study including 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) underwent aortocoronary bypass (ACVB) with extracorporeal circulation (ECC), while patients in group 3 (n = 20) had carotid surgery. Anaesthesia, coronary-bypass procedures and infusion regime were standardized. The flow rate during ECC was maintained at 2.41/min/m2 and the rectal temperature between 33 degrees and 34 degrees C. Arterial and urine specimens for the determination of plasma and urine levels of cefamandole were taken at definite times. Autologous blood salvage during operation was performed with haemofiltration techniques (HF) in group 1 (HF 80, Fresenius, Bad Homburg, Germany) and with cell separation techniques (CS) in group 2 (Hemonetics III, Hemonetics). Plasma and urine cefamandole levels were measured by high-pressure liquid chromatography (HPLC). RESULTS. After administration of 2 g cefamandole mean peak levels of 404.6 +/- 141.7 micrograms/ml were seen. Because of haemodilution at the beginning of extracorporeal circulation, group 1 and 2 showed much lower cefamandole plasma levels, 22.1 +/- 11.6 micrograms/ml and 24.3 +/- 14.4 micrograms/ml, than group 3 (after the same time course), with 47.4 +/- 19.1 micrograms/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 cefamandole plasma levels at the beginning of extracorporeal circulation (P < 0.001). No correlation could be seen for the plasma concentration after discontinuation of the extracorporeal circulation and the duration of extracorporeal circulation. The volume of autologous red packed cells and the enclosed amount of cefamandole showed a significant difference (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 cefamandole level after transfusion of autologous blood displayed a significant correlation (p < 0.01) with cefamandole concentration in the autologous red packed cells. Transfusion of the autologous blood produced no significant increase in plasma cefamandole levels. With an operation time of more than 2.5 h during ECC the cefamandole plasma level decreased below the necessary minimal inhibitory concentration (MIC90), particularly for gram-negative bacteria. CONCLUSION. Additional administration of 1 g cefamandole shortly before the beginning of cardiopulmonary bypass is recommended, particularly for surgical procedures with ECC of more than 2.5 h. Adjustment of drug dosage prior to or during surgery may be required to optimize therapy, but before this can be achieved precisely, more information on drug disposition during the operative procedures is needed.