The Pharmacokinetics of a Single Dose of Gentamicin (4 mg/kg) as Prophylaxis in Cardiac Surgery Requiring Cardiopulmonary Bypass

Abstract

Background: Cardiopulmonary bypass has complex effects on drug pharmacokinetics, which is important when considering the use of once-daily aminoglycoside regimens during cardiac surgery. Aim: To study the effects of cardiopulmonary bypass on the pharmacokinetics of a single dose of gentamicin (4 mg/kg). Patients and methods: Nine patients undergoing valve replacement surgery were given a single dose of gentamicin (4 mg/kg) at induction of anaesthesia and blood was taken for assay at 0, 0.5. 1. 1.5, 2, 2.5, 3, 4, 6, 10, 16, 22 and 24 h following administration. The mean (range) gentamicin Cmax was 18.7 (12.4–26.3) mg/litre. Three patients had concentrations of gentamicin after 24 h of > 1 mg/litre. During cardiopulmonary bypass, the mean (range) gentamicin half-life (tt/2) was 5.1 (2.0–15.1) h and post-bypass the t1/2 was 7.1 (3.0–13.9) h. Conclusion: There is significant correlation between the elimination t1/2 and length of cardiopulmonary bypass ( r = 0.89, P < 0.01). These results suggest that gentamicin excretion is delayed following cardiopulmonary bypass so that with dose regimens of < 4 mg/kg there is a risk of toxicity