Pannu and Gibney modeling (UKM). Absolute concentrations of urea and creatinine are difficult to interpret; however, clearance of these marker substances appears to be the best measurement of therapy dose as it considers generation rates as well as plasma clearance. While quantification of dialysis dose using UKM is intuitive with intermittent therapies, methods for measuring clearance in CRRT are variable, hampered in part by a lack of understanding of what parameters should be used to compute dialysis dosage. The total solute clearance in CRRT techniques is the sum of the convective and diffusive clearances (Siegler and Teehan 1987), which is, in practical terms, the hourly volume of effluent fluid (ultrafiltrate and dialysate). Since the molecular weight cut off for the membranes is > 20 000 Daltons, most low and middle molecular weight substances have sieving coefficients (SC) of 1. Convective clearance is therefore directly proportional to the amount of filtrate produced. Small molecules are less dependent on convective clearance and are more effectively transferred by diffusion. Slow dialysate flow rates (1–2 L/h) allow for complete saturation of the dialysate fluid with solutes. CRRT clearance is commonly expressed as the L/kg/h of effluent. At the present time, a UKM-based calculation of plasma solute clearance is the most common method measurement of dialysis dosage with both intermittent and continuous forms of dialysis, although it is not entirely clear that the calculated clearance values can be directly compared (Siegler and Teehan 1987). This calculation is called Kt/V, where K is clearance, t is duration of dialysis, and V is the volume of distribution of urea. The limitation of this method rests in the observation that critically ill patients with ARF are frequently catabolic and have highly variable fluid volumes; both conditions violate several of the assumptions implicit in urea kinetic modeling. Quantification of solute clearance using dialysate concentrations of clearance markers (calculation of a solute removal index [SRI]) avoids some of the limitations of blood-based clearance calculations. There is no consensus as to which method should be used in all clinical situations. What is the appropriate dose of dialysis? The notion of dialysis dose quantification in ARF has been controversial, due in part, to the lack of convincing evidence that azotemia control affects outcome in patients with either acute or chronic renal failure. At the present time there is no consensus as to what the minimal dialysis dose should be in patients with ARF. Extrapolating data from the end- stage renal disease (ESRD) population (Gotch and Sargent 1985), it seems reasonable to suggest a minimum Kt/V of 1.2 should be delivered at least three times a week in patients with ARF. However, several recent studies support the belief that more intensive dialysis may be beneficial in this patient group. A randomized dose-intensity study of CVVH in 425 critically ill patients demonstrated a significant decrease in patient mortality when ultrafiltration rates of 35 mL/kg/h (approximately 3 L/h in a 70 kg male) were used as compared with 20 mL/kg/h (Ronco et al 2000). A randomized trial of intermittent hemodialysis comparing daily with alternate day dialysis showed a reduction in mortality from 46% to 28% (p < 0.05) (Schiffl et al 2002). Unfortunately the delivered dialysis dose in the alternative day group as measured by weekly Kt/V was less than 3.6, the minimally acceptable dose in chronic dialysis patients, thus the issue of minimal adequate dose remains unresolved. Practical issues regarding renal replacement therapy in the ICU Vascular access Vascular access for acute intermittent hemodialysis must be obtained using double lumen dialysis catheters. These may be inserted in the internal jugular, subclavian, or femoral veins. If possible, subclavian vein cannulation should be avoided because of a high incidence of subsequent venous stenosis, which may significantly complicate venous access if chronic hemodialysis is required (Stalter et al 1986; Cimochowski et al 1990; Bambauer et al 1994). Blood recirculation from the venous to the arterial port can reduce the effectiveness of dialytic therapies, particularly during IHD. Use of a short 13.5-cm catheter in the femoral vein may result in up to 23% blood flow recirculation and can be avoided by using longer catheters (19–25 cms) when using the femoral vein for vascular access (Kelber et al 1993). Access to blood supply for the extra corporeal circuit varies with CRRT techniques. Arteriovenous techniques, which have largely fallen out of favor, generally require cannulation of the femoral artery and the femoral vein. The variable blood flow rates lead to a higher risk of thrombosis. In general, large bore, small length catheters are preferable for AV procedures to permit a high blood flow rate. In pumped (venovenous) systems double lumen venous catheters are commonly used; the size should be selected based on the site of insertion to optimize flow. 144 Therapeutics and Clinical Risk Management 2005:1(2)