Membranes Membrane characteristics that should be considered when selecting membranes for hemodialysis or CRRT include solute removal, water permeability, and biocompatibility. Dialyzer efficiency (KoA) is extremely important in IHD where therapy is administered over a relatively short period of time with high blood and dialysate flow rates. Generally speaking, the efficiency of small solute clearance in CRRT is largely determined by dialysate/ultrafiltration flow rate; therefore, solute removal characteristics are not an important factor in choosing a dialysis membrane. High flux membranes, which are designed to provide high water permeability, are generally recommended for hemofiltration procedures. Finally, although there is no conclusive evidence that membrane biocompatibility affects patient outcome, there is general consensus (Kellum, Mehta, et al 2002) that the use of synthetic membranes is preferable over cellulose- based membranes for the treatment of patients with ARF. Replacement/Dialysate solutions Dialysate for intermittent hemodialysis is generally produced on-line by the dialysis machine from a combination of treated water and various electrolytes. There are stringent standards for water quality in the hemodialysis unit set out by the American Association of Medical Instrumentation (AAMI). Water purification is generally achieved by treatment with reverse osmosis, deionization, and the use of charcoal filters. Dialysate water is not required to be sterile as there is no contact between blood and dialysate. All CRRT techniques other than slow continuous ultrafiltration (SCUF) require the use of sterile dialysate/ replacement fluids to compensate for the ultrafiltrate removed. Although dialysate does not come into direct contact with blood given the low blood-side pressures, back- filtration (dialysate to blood) may readily occur, particularly with high permeability membranes (Golper 1989). Optimal dialysate/replacement solution approximates normal plasma water composition, replacing electrolytes and minerals in physiologic concentrations without replacing the metabolic solutes, which accumulate in renal failure. The composition of these solutions can be varied extensively to achieve specific metabolic goals (eg, bicarbonate-based solutions can be used to correct acidemia and the electrolyte content can be altered to correct electrolyte imbalance) (Macias and Clark 1996; Palevsky 1996). A limitation of using sterile solution for CRRT is that they are acetate or Therapeutics and Clinical Risk Management 2005:1(2) Renal replacement therapy lactate based and the capacity to convert these buffers to bicarbonate may be limited in patients with multiple organ failure (Levraut 1997). More recently, bicarbonate-based solutions, which are better tolerated than lactate- or acetate- based solutions, have become commercially available (Zimmerman et al 1999). When citrate anticoagulation is used in CRRT, modifications are necessary in both the replacement fluid and dialysate; often necessitating the use of customized, locally prepared solutions as commercially available solutions are not widely available. Citrate is metabolized to bicarbonate by the liver; therefore buffer is not generally required in the dialysate. Similarly, dialysate used in citrate regional anticoagulation is generally hyponatremic to prevent hypernatremia, and it is recommended that fluids are calcium free. Few commercially available calcium free, bicarbonate-based CRRT fluids have been available until recently. This has led many centers to produce such fluids in-house using pharmacy total parenteral nutritional (TPN) manufacturing facilities. Manufacturing error in the pharmacy led to pharmacy technicians using concentrated potassium chloride instead of concentrated sodium chloride in the production of CRRT fluid in Calgary, Canada, in the last year and resulted in the deaths of 2 critically ill patients. Both electrolyte solutions had been provided in almost identically labeled containers. A commercially available solution is supplied as a concentrate, which is added to 3-L bags of sterile water. Failure by critical care bedside nurses to add the concentrate to the sterile water has resulted in the deaths of 2 patients in Toronto, Canada, from massive hemolysis. These tragedies underscore the importance of using commercially prepared solutions; if addition of concentrate to sterile water is required, this should be done in a pharmacy setting. Anticoagulation Anticoagulation is an essential component of all blood-based renal replacement therapies, including CRRT. The passage of blood through an extracorporeal circuit causes platelet activation and induces a variety of inflammatory and prothrombotic mediators, resulting in fibrin deposition on filter membranes. This not only affects filter longevity, but may also decrease dialyzer efficacy in terms of water and solute removal. If anticoagulation is insufficient, filtration performance deteriorates and the filter may clot, contributing to blood loss and additional costs related to filter replacement. Excessive anticoagulation may result in 145