Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing.

OBJECTIVE: Drug dosing during continuous venovenous hemofiltration (CVVH) is based partly upon the CVVH clearance (Cl(CVVH)) of the drug. Cl(CVVH) is the product of the sieving coefficient (SC) and ultrafiltration rate (Q(uf)). Although it has been suggested that the SC can be replaced by the fraction of a drug not bound to protein (F(up)), the F(up) values as reported in the literature may not reflect the protein binding in critically ill patients with renal failure. We compared the observed Cl(CVVH) (SC x Q(uf)) with the estimated Cl(CVVH) (estimated F(UP) x Q(uf)) and determined the effect on the maintenance dose multiplication factor (MDMF). DESIGN AND
SETTING: Clinical study in a mixed ICU in a university hospital. PATIENTS: 45 oligoanuric patients on CVVH (2 l/h).
INTERVENTIONS: Timed blood and ultrafiltrate samples. MEASUREMENTS AND
RESULTS: Amoxicillin, ceftazidime, ciprofloxacin, fluconazole, metronidazole, and vancomycin were easily filtered (mean SC > 0.7) but not flucloxacillin (mean SC 0.3). Predicted and observed Cl(CVVH) corresponded only for fluconazole and metronidazole. The difference between observed and predicted MDMF was small for all drugs, with the exception of ceftazidime (mean 0.25, 95% CI -0.96 to 1.48) and vancomycin (0.05, -1.34 to 1.45). However, this difference was clinically relevant only for vancomycin, because of its narrow therapeutic index.
CONCLUSIONS: Dosing based on predicted CVVH removal provides an as reliable estimate than that based on observed CVVH removal except for those antibiotics that have both a narrow therapeutic index and a predominantly renal clearance (e.g., vancomycin).