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Apheresis is the process of separating the blood and removing or manipulating a cellular or plasma component for therapeutic benefit. An apheresis procedure, or series of procedures, may be indicated in the critical care setting as primary or adjunctive therapy for certain hematologic, neurologic, renal, and autoimmune/rheumatologic disorders. Optimal management of severely ill patients undergoing apheresis requires a working knowledge of the technical, methodological, and therapeutic considerations. These considerations include instrument hardware and separation methods, vascular access requirements, hemodynamic and hemostatic effects of the procedures, exposure to anticoagulants and homologous blood products, physiological variables affecting blood/plasma processing efficiency, and therapeutic endpoints for specific indications. Part 1 of this review will discuss each of those technological considerations and the basic physiological principles that guide this form of therapy. Part 2 of this series will deal with the clinical indications and applications for specific disorders that are most likely to affect patients in the intensive care unit.