INFLAMMATORY MEDIATORS IN SEPSIS - RATIONALE FOR EXTRACORPOREAL THERAPIES

Sepsis is an increasingly common cause of morbidity and mortality, esp ecially in patients in the intensive care units, Sepsis represents a s ystemic response to infection, and is part of a broader syndrome calle d systemic inflammatory response syndrome (SIRS). SIRS is an exagerate d host defense response to different triggering factors such as gram-n egative bacterial endotoxin, trauma, and burns leading to the release of biologically active mediators such as cytokines, arachidonic acid m etabolites, platelet activating factor, and nitric oxide, Proinflammat ory cytokines such as tumor necrosis factor and interleukin-l target s econdary cellular sites and activate several inflammatory cascades, le ading to organ dysfunction and multiple organ failure, Conventional th erapy of sepsis involves treatment of the nidus of infection, and hemo dynamic and respiratory support, Innovative strategies targeting endot oxin and inflammatory mediators of SIRS have been effective in animal models, However, human trials using antiendotoxin or anticytokine stra tegies have been disappointing, partly because of the enormous complex ity of the pathogenesis of sepsis, and the futility of attempts to blo ck a single inflammatory mediator, while ignoring the interplay of dif ferent biologically active mediators, These frustrations have led to a renewed interest in extracorporeal therapies such as hemo(dia)filtrat ion, plasma exchange, and hemoperfusion using activated charcoal to de crease circulating levels of inflammatory mediators, and hemoperfusion using polymyxin-B immobilized polystyrene fibers to adsorb circulatin g bacterial endotoxin. These promising adjunctive therapies are often nonselective, but appear to have additional therapeutic potential, as part of the complex therapy of sepsis, However, their efficacy in the clinical situation awaits further investigation. (C) 1996 by The Natio nal Kidney Foundation, Inc.