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

Abstract

Both aprotinin and gentamicin-vancomycin antibiotic prophylaxis have been used widely in cardiac surgery to prevent bleeding and infections, respectively. As the drugs are excreted almost entirely by glomerular filtration, we investigated their action on renal function when administered either separately or together. To increase consistency, we measured serum concentrations of creatinine and cystatin C, a new marker of glomerular filtration rate, that many recent studies have shown to be more sensitive than serum creatinine. One hundred patients undergoing coronary artery bypass surgery were allocated randomly to one of four groups: group A received antibiotic prophylaxis with cefamandole and no aprotinin; group B received cefamandole and high-dose aprotinin; group C received antibiotic prophylaxis with gentamicin and vancomycin, but no aprotinin; and group D received both high-dose aprotinin and gentamicin-vancomycin antibiotic prophylaxis. Data from 84 patients, for whom data collection was complete, were analysed. In the first week after operation, mean serum concentrations of cystatin C and creatinine either remained constant or decreased slowly in all groups, except for group D. In group D, both markers increased gradually from postoperative day 2 onwards. The increase in cystatin C was significant on postoperative day 5 (from mean 1.02 (SD 0.11) 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 on postoperative 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 administration of high-dose aprotinin and prophylactic use of gentamicin with vancomycin increased serum concentrations of cystatin C and creatinine in the first postoperative week in patients undergoing cardiac surgery.

Osteocalcin and the hormonal, inflammatory and metabolic response to major orthopaedic surgery

“…Simultaneously, a decrease in arterial pressure would stimulate the renin‐angiotensin axis, causing preferential constriction of efferent arterioles, thus increasing glomerular filtration rate and urine output. Similar changes have been found in patients undergoing coronary artery bypass grafting [37].…”

Effects of Aprotinin Dosage on Renal Function

“…Some studies investigating specifically the influence of aprotinin on renal function reported small but significant differences in renal function compared with control patients. 13 This renal impairment may be aggravated in the presence of other nephrotoxic drugs such as aminoglycosides 36 or angiotensin-converting enzyme inhibitors. 37 The influence of aprotinin on tubular function without tubular damage was confirmed by others.…”

Perioperative antibiotic prophylaxis in paediatric cardiac surgery

“…First is the development of hypotension, flushing or red-man syndrome, bronchospasm, and even cardiac arrest associated with the administration of vancomycin. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] The mechanism of action is thought to be nonimmunologic release of histamine. [50][51][52] It requires no previous exposure to vancomycin, and is classified as anaphylactoid.…”

“…In children as well as adults, cardiopulmonary bypass can modify the usual pharmacokinetics of gentamicin as a result of the greater volume of distribution secondary to priming, immature renal function, frequent use of hypothermia, ultra filtration and aprotinin, altered circulatory physiology and transient renal dysfunction. 48,[58][59][60][61][62][63] This results in the lack of a steady state and unpredictable peaks and troughs that, in turn, could have potential renal, vestibular and cochlear toxicity. [64][65][66] Additionally, there is currently no evidence to suggest a higher rate of infection with gram-negative organisms following paediatric cardiac surgery; even in those undergoing delayed sternal closure.…”