Single dose kinetics of piperacillin during continuous arteriovenous hemodialysis in intensive care patients.

Piperacillin (Pi) kinetics in patients with acute renal failure treated by continuous arteriovenous hemodialysis (CAVHD) are not known. Therefore, dosing regimens have been based on kinetic data derived from patients with chronic renal failure and principal pharmacokinetic considerations [Reetze-Bonorden et al. 1993]. From these estimations it has been predicted that approximately 30% of the dose of Pi is removed by CAVHD (dialysate/ultrafiltrate (D/UF) flow rate 1.5 liter/hour). To confirm this estimate single dose (4g i.v.) Pi kinetics were studied in 12 intensive care patients with anuric acute renal failure due to septicemia treated by CAVHD. Pi plasma and D/UF levels were measured by HPLC. Sieving/Saturation of Pi in the D/UF was 0.71 +/- 0.21 (+/- SD). With a mean D/UF flow rate of 20.4 +/- 1.5 ml/min, the mean extracorporal clearance (Clextra) was 12.2 +/- 1.0 ml/min and accounted for 29% (range 14-48%) of total body clearance (ClB = 47.1 +/- 22.3 ml/min). In 7 out of 12 patients the fraction of the dose eliminated by CAVHD reached a significant value above 25%. The mean volume of distribution (Vd) and elimination half life (t1/2) were 25.8 +/- 3.8 liter and 7.4 +/- 2.9 hours, respectively. In conclusion the extent of extracorporal elimination of Pi by CAVHD was well in agreement with the estimation previously published. In intensive care patients with acute renal failure on continuous hemodialysis Pi dosing should take into account the possibly significant elimination of Pi. The usual dose for anuric patients may be increased by 50% to avoid underdosing in these critically ill patients.