High-dose aprotinin with gentamicin-vancomycin antibiotic prophylaxis increases blood concentrations of creatinine and cystatin C in patients undergoing coronary artery bypass grafting

Both aprotinin and gentamicin-vancomycin antibiotic prophylaxis have beenused widely in cardiac surgery to prevent bleeding and infections,respectively. As the drugs are excreted almost entirely by glomerularfiltration, we investigated their action on renal function whenadministered either separately or together. To increase consistency, wemeasured serum concentrations of creatinine and cystatin C, a new marker ofglomerular filtration rate, that many recent studies have shown to be moresensitive than serum creatinine. One hundred patients undergoing coronaryartery bypass surgery were allocated randomly to one of four groups: groupA received antibiotic prophylaxis with cefamandole and no aprotinin; groupB received cefamandole and high- dose aprotinin; group C receivedantibiotic prophylaxis with gentamicin and vancomycin, but no aprotinin;and group D received both high-dose aprotinin and gentamicin-vancomycinantibiotic prophylaxis. Data from 84 patients, for whom data collection wascomplete, were analysed. In the first week after operation, mean serumconcentrations of cystatin C and creatinine either remained constant ordecreased slowly in all groups, except for group D. In group D, bothmarkers increased gradually from postoperative day 2 onwards. The increasein cystatin C was significant on postoperative day 5 (from mean 1.02 (SD0.11) mg litre-1 before operation to 1.35 (0.32) mg litre-1; P < 0.05),reaching a peak on postoperative day 7 (1.45 (0.35) mg litre-1; P <0.05), while the increase in creatinine concentration was significant onpostoperative day 6 (from 1.05 (0.16) mg dl-1 before operation to 1.29(0.34) mg dl-1; P < 0.05). We conclude that simultaneous administrationof high-dose aprotinin and prophylactic use of gentamicin with vancomycinincreased serum concentrations of cystatin C and creatinine in the firstpostoperative week in patients undergoing cardiac surgery.