Detoxification of plasma containing lipopolysaccharide by adsorption

We compared the ability of 13 materials, all with known affinity for lipopolysaccharide (LPS), to remove LPS from water, pooled normal human plasma, and plasma from a patient with Gram-negative bacterial sepsis. Escherichia coli O111:B4 LPS was added to water and pooled normal human plasma to a concentration of 200 ng/ml and aliquots were adsorbed in parallel with each of the materials. Plasma containing 25 ng/ml of LPS was obtained by plasmapheresis from a patient with fatal Klebsiella pneumoniae sepsis and was similarly adsorbed. Ethanolamine bound to Sepharose 4B served as a control adsorbent. LPS was most readily removed from water and least readily removed from plasma obtained from the patient with sepsis. Nonetheless, some materials removed substantial quantities of LPS from the patient's plasma. Upon ip injection of control-adsorbed patient's plasma into LPS-sensitized mice, death occurred in 13 of 13 mice within 12 h. In contrast, when this plasma was first adsorbed with activated charcoal, Kaopectate, or polymyxin B bound to Sepharose 4B, death occurred 12 h after challenge in 0/13, 0/13, and 2/13 mice, respectively (p less than .0001 by actuarial life table analysis of survival distributions). Thus, plasma that contains bacterial toxins produced during Gram-negative bacterial sepsis can be detoxified by adsorption.