Guidelines for drug dosing during continuous renal replacement therapy

Abstract

Dose amount and frequency can be calculated from a knowledge of the basic pharmacokinetic factors relating to distribution and elimination of a drug within the body, along with a knowledge of the desired drug concentration in plasma. Acute renal failure affects both distribution and elimination of many drugs, so must be taken into account in making decisions about drug dosing. In many parts of the world, continuous renal replacement techniques have become the mainstay of treatment for acute renal failure in critical illness. These techniques include continuous arteriovenous or veno-venous haemofiltration (CAVH, CVVH), and a combination of haemofiltration and haemodialysis: continuous arterio-venous or veno-venous haemodiafiltration (CAVHDF, CVVHDF). Haemofiltration is a technique which uses convection (i.e. bulk flow) of filtrate across a highly permeable membrane to remove solutes from the bloodstream. Its effectiveness in drug clearance thus, depends largely upon filtrate flow rate. Haemodialysis, on the other hand, uses diffusive clearance to remove solutes from the bloodstream. This is a very efficient process with molecules of small to moderate size (< 500D), less so with compounds of higher molecular weight. Although CVVHDF includes a component of haemofiltration, the filtration flow rates achieved are generally relatively low (of the order of 500m1/hr), and this means that the most significant contribution of CVVHDF to drug excretion occurs through diffusion, and thus depends upon dialysate flow rate. Because of the limitations of haemodialysis in removing large molecules, CVVHDF with a given dialysate flow rate is less efficient in the removal of some drugs than CVVH with an equivalent filtrate flow rate. The only important class of drugs to which this applies in ICU is the glycopeptide antibiotics (vancomycin and teicoplanin), which have molecular weights between 1,100–1,800D.