Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration

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Abstract
Objective There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of less than 1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration. Design Prospective laboratory study. Subjects Normal human subjects. Interventions Radioactive [sup 3 H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined. Measurements Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor. Main Results [sup 3 H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 plus minus 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p less than .001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 plus minus 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [sup 3 H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 plus minus 12.2%) than with washed blood (1.1 plus minus 0.3%) or plasma (11.9 plus minus 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C. Conclusions These studies provide experimental evidence for the prompt, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis. (Crit Care Med 1995; 23:99-107)