Pharmacokinetics and drug dosing adjustments during continuous venovenous hemofiltration or hemodiafiltration in critically ill patients

Abstract

Continuous renal replacement therapy (CRRT) in critically ill patients with renal failure may significantly increase drug clearance, requiring drug dosing adjustments. Drugs significantly eliminated by the kidney often undergo substantial removal during CRRT, and a supplemental dose corresponding to the amount of drug removed by CRRT should be administered. Clearance by CRRT can either be measured or estimated. The high-flux membranes used in CRRT make no filtration barrier to most drugs, and the filtrate concentration can be estimated by the unbound fraction of the drug in plasma. When adding dialysis to filtration, this approach overestimates drug clearance, and a correcting factor should be used. A method for estimating drug clearance as a function of creatinine clearance is also suggested, but it has the same limitations in overestimating drug clearance when dialysis is combined with filtration. For non-toxic drugs, doses can safely be increased 30% above actual estimates to ensure adequate dosing. For drugs with a narrow therapeutical margin, monitoring plasma concentrations are mandatory. When appropriate, the use of a readily available reference for drug dosing is recommended.