Clearance of gentamicin during cardiac surgery.

Treatment with an aminoglycoside plus flucloxacillin is commonly used to prevent wound infection and endocarditis after cardiac surgery. Cardiopulmonary bypass, blood transfusion and the lack of a steady state greatly affect handling of gentamicin. Urinary gentamicin excretion is not predictable in terms of preoperative risk factors possibly because there is no clear relationship between serum levels and gentamicin clearance. A study was performed to determine whether the existing prophylactic regimen gave adequate serum levels during surgery and to compare renal excretion of gentamicin and the trough serum levels. Ten patients received gentamicin (1.5 mg/kg at the start of surgery followed by 80 mg tds for 2 days) and flucloxacillin 500 mg qds for 2 days. Serum and urinary concentrations of gentamicin were assayed during surgery and in the early postoperative period. The median apparent serum half-life during the first 8 h was 2.5 h (95%CI 1.7-3.2 h). The median gentamicin clearance was 37 mL/min(95%CI 23-64 mL/min) and the creatinine clearance 85 mL/min (95%CI 72-210 mL/min). Serum levels remained above 1 mg/L during surgery but urinary concentrations varied between 0.4 and 364 mg/L (median 70 mg/L). At 24 h (but not 8 or 16 h), trough serum levels appeared to be related to the amount of gentamicin excreted but the relationship was not quite statistically significant (P = 0.057). Despite the effects of cardiopulmonary bypass, therapeutic serum gentamicin levels were maintained during surgery and reduced renal excretion in the postoperative period was associated with raised levels.

Antibiotic prophylaxis in cardiac surgery: factors associated with potentially toxic serum concentrations of gentamicin.

Aminoglycosides are commonly used with flucloxacillin in the prevention of wound infection and endocarditis after cardiac surgery. Earlier studies suggested that the use of aminoglycosides is associated with a small but significant rise in serum creatinine. A regression analysis was performed to identify the preoperative and postoperative factors of importance in determining serum gentamicin concentrations. Serum assays might then be confined to those at particular risk of elevated serum levels. Patients received gentamicin 1.5 mg/kg at the start of surgery followed by 80 mg tds for two days in addition to flucloxacillin. Trough and peak serum gentamicin concentrations were assayed on the first and second days after surgery and urine concentrations were measured with each full catheter bag. Patient characteristics, drug therapy, operation, fluid balance and routine investigations were recorded. A total of 95 of 104 patients were evaluable. Linear discriminant analysis of factors selected by forward stepwise regression identified ten of the 15 patients with subsequent elevated gentamicin concentrations, by using age, and preoperative serum creatinine, systolic blood pressure and serum aspartate transaminase. After operation, factors such as serum creatinine, the quantity of frusemide administered in 24 h, and the integral of the systolic blood pressure over 24 h identified 12 of the 15 patients. However, no satisfactory model could predict urinary concentrations. The discriminant function using preoperative factors prospectively identified 11 of 12 patients with elevated trough levels from a total of 101 further patients. Postoperative gentamicin concentrations cannot reliably be predicted from patient characteristics. Trough assays should be performed or prophylactic courses limited to 24 h.