Dosing Recommendations for Continuous Venovenous Hemodiafiltration with AN69 Filter Membranes and Prismaflex Dialyzers.

BACKGROUND Continuous renal replacement therapy is used to manage fluid and solute imbalances in critically ill patients but may affect the clearance of concurrently administered drugs. The impact of continuous renal replacement therapy on pharmacokinetics has been summarized, but previous reports have included studies involving various modes of therapy, filter membranes, and brands of dialyzers, which makes it difficult to apply the recommendations to individual patients. In Canada, continuous venovenous hemodiafiltration (CVVHDF) with a Prismaflex dialyzer machine (Gambro, Saint-Léonard, Quebec) and AN69 filter membranes is the most common mode of continuous renal replacement therapy for critically ill patients. OBJECTIVE To develop a set of dosage recommendations for commonly encountered medications used in treating critically ill patients who are undergoing CVVHDF with a Prismaflex dialyzer and AN69 filter membranes. METHODS A literature search was conducted to identify studies of the pharmacokinetics and disposition of drugs in patients undergoing CVVHDF via a Prismaflex dialyzer (sold under 3 brand names: Gambro, Hospal, and Prima) equipped with polyacrylonitrile (AN69) filter membranes. From each study, the mean total clearance of each study medication during CVVHDF was extracted and compared with clearance of the drug in patients not undergoing CVVHDF, to produce dosage guidelines for patients undergoing CVVHDF. RESULTS A total of 22 studies of 14 medications were included in the final review. For most of the drugs, the total clearance during CVVHDF was less than clearance in patients whose renal function was presumed to be normal. Fluconazole and moxifloxacin had greater total clearance during CVVHDF, but a dose adjustment during CVVHDF was deemed necessary only for fluconazole. CONCLUSIONS Dosing recommendations were created for concurrently administered drugs for patients undergoing treatment with this particular CVVHDF equipment. Patient-specific factors and clinical judgement should also be taken into account.