DETERMINANTS OF VANCOMYCIN CLEARANCE BY CONTINUOUS VENOVENOUS HEMOFILTRATION AND CONTINUOUS VENOVENOUS HEMODIALYSIS

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage reg imen adjustment techniques have been proposed for these patients, ther e is little quantitative data to guide the individualization of vancom ycin therapy in acute renal failure patients who are receiving continu ous renal replacement therapy (CRRT). To determine appropriate vancomy cin dosing strategies for patients receiving continuous venovenous hem ofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis pat ients with three hemofilters: an acrylonitrile copolymer 0.6 m(2) (AN6 9), polymethylmethacrylate 2.1 m(2) (PMMA), and polysulfone 0.65 m(2) (PS), Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study, The concentration of v ancomycin in multiple plasma and dialysate/ultrafiltrate samples was d etermined by EMIT (Syva, Pale Alto, CA), The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as t he main effects and patient as a random effect. Vancomycin was moderat ely protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly corre lated with the free fraction of vancomycin (P = 0.01; r(2) = 0.465), S ignificant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r(2) = 0.880); PMMA(slope = 0.853; r(2) = 0.966); and PS (slop e = 0.658; r(2) = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essen tially constant at all Q(B)s for all three filters. Thus, the clearanc e of vancomycin was not membrane dependent during CVVH, However, durin g CVVHD, membrane dependence of vancomycin clearance was noted at a Q( DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI ) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failu re patients. Dosing strategies for individualization of vancomycin the rapy in patients receiving CVVH and CVVHD are proposed. (C) 1998 by th e National Kidney Foundation, Inc.