Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration

Abstract

Aims: To investigate the pharmacokinetics of vancomycin in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF), a continuous renal replacement therapy (CRRT) and to see if routine measures approximate vancomycin clearance.

Methods: Pharmacokinetic profiles (15) of initial and steady-state doses of 750 mg twice daily intravenous vancomycin were obtained from blood and ultrafiltrate samples from 10 critically ill patients in the intensive care unit, with acute renal failure on CVVHDF (1 l h(-1) dialysate plus 2 l h(-1) filtration solution; 3 l h(-1) effluent; extracorporeal blood flow 200 ml min(-1)).

Results: CVVHDF clearance of vancomycin was 1.8 +/- 0.4 l h(-1) (30 +/- 6.7 ml min(-1)). This was 1.3-7.2 times that reported previously for vancomycin using other forms of CRRT. Total vancomycin body clearance was 2.5 +/- 0.7 l h(-1) (41.7 +/- 11.7 ml min(-1)). The clearance of vancomycin by CVVHDF was 76 +/- 16.5% of the total body clearance. CVVHDF removed approximately half the vancomycin dose during the 12-h period (A(CVVHDF) = 413 mg). The fraction eliminated by all routes was 60%. The sieving coefficient for vancomycin was 0.7 +/- 0.1 and for urea was 0.8 +/- 0.06.

Conclusions: Vancomycin is cleared effectively by CVVHDF. Clearance was faster than other forms of CRRT, therefore doses need to be relatively high. Urea clearance slightly overestimates vancomycin clearance. The administered doses of 750 mg every 12 h were too high and accumulation occurred, as only approximately 60% of a dose was cleared over this period. The maintenance dose required to achieve a target average steady-state plasma concentration of 15 mg l(-1) can be calculated as 450 mg every 12 h.

Figure 1

Concentration–time data for vancomycin 750 mg administered intravenously every 12 h (mean ± SD). Initial doses (patients 1–3, 5, 8 and 10) (▴); Subsequent doses (patients 1–4, 6–10) (▪)

Figure 2

Mean concentration of vancomycin in effluent collected hourly (mean ± SD). Initial doses (Profile A only) or patients 1–3, 5, 8 and 10 (); Subsequent doses (Profile B only) or patients 1–4, 6, 7, 8, 9 and 10 ()

Figure 3

Clearance of vancomycin and urea by continuous venovenous haemodiafiltration (CVVHDF) calculated at 4-h intervals (mean ± SD). Vancomycin clearances (♦); Urea clearances (▪)