Tetta C, Mariano F, Buades J, Ronco C, Wratten M L, Camussi G
Clinical and Laboratory Research Department, Bellco, Mirandola (Modena), Italy.
Am J Kidney Dis. 1997 Nov;30(5 Suppl 4):S57-65. doi: 10.1016/s0272-6386(97)90543-6.
Sepsis can be considered a systemic inflammatory response syndrome (SIRS) caused by infection. When an excessive and/or persistent activation of humoral and cellular mechanisms of host defense is present, an exaggerated and generalized activation of inflammatory mechanisms can lead to a multiple organ dysfunction syndrome. Mediators thought to be involved in this syndrome include the major plasma cascade systems (complement, coagulation, and fibrinolytic systems) and soluble cell-derived mediators (cytokines, reactive oxygen species, platelet-activating factor (PAF), arachidonic acid metabolites, and nitric oxide and related compounds). Several findings indicate that among these mediators, PAF may exert an important role in the pathophysiology of septic shock. Evidence is accumulating that in human sepsis this scenario is far more complicated and that removal of inflammatory mediator excess from plasma, rather than blockade of their potentially beneficial local production, might provide a rationale for the use of continuous renal replacement therapy (CRRT). There is an emerging view that CRRT should be considered in the light of broader concept (ie, the use of blood purification for the treatment of sepsis). Recent studies, performed in an experimental model of continuous arteriovenous hemofiltration with exogenous PAF, demonstrated that polysulfone membranes can adsorb substantial amounts of biologically active PAF. These studies also showed that the removal of this mediator occurs by a two-step process involving early adsorption followed by ultrafiltration. Although the removal of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), remains controversial, mainly because of differences in membrane used, operational conditions, and inter- and intra-assay variability, the crucial point is that no evidence has yet been given to show real benefit from CRRT in significantly reducing the plasma concentration of cytokines. The net advantage of CRRT, however, may not only be the removal of cytokines per se, but also the simultaneous elimination of cytokine-inducing substances. Experimental and human studies will be discussed as to whether extracorporeal treatments may remove an excess of circulating cytokines, either by increasing the turnover rate (the so-called high-volume hemofiltration), or by using sorbent systems to regenerate plasma filtrate.
脓毒症可被视为由感染引起的全身炎症反应综合征（SIRS）。当宿主防御的体液和细胞机制出现过度和/或持续激活时，炎症机制的过度和全身性激活可导致多器官功能障碍综合征。被认为参与该综合征的介质包括主要的血浆级联系统（补体、凝血和纤溶系统）和可溶性细胞衍生介质（细胞因子、活性氧、血小板活化因子（PAF）、花生四烯酸代谢产物以及一氧化氮和相关化合物）。多项研究结果表明，在这些介质中，PAF可能在感染性休克的病理生理学中发挥重要作用。越来越多的证据表明，在人类脓毒症中，情况要复杂得多，从血浆中清除过量的炎症介质，而非阻断其潜在有益的局部产生，可能为使用连续性肾脏替代治疗（CRRT）提供理论依据。一种新出现的观点认为，应从更广泛的概念（即使用血液净化治疗脓毒症）来考虑CRRT。最近在外源性PAF的持续性动静脉血液滤过实验模型中进行的研究表明，聚砜膜可吸附大量具有生物活性的PAF。这些研究还表明，这种介质的清除通过两步过程发生，包括早期吸附，随后是超滤。尽管细胞因子如肿瘤坏死因子-α（TNF-α）的清除仍存在争议，主要原因在于所用膜的差异、操作条件以及测定间和测定内的变异性，但关键在于尚无证据表明CRRT在显著降低细胞因子血浆浓度方面具有实际益处。然而，CRRT的净优势可能不仅在于细胞因子本身的清除，还在于同时清除细胞因子诱导物质。将讨论实验和人体研究，以探讨体外治疗是否可通过提高周转率（即所谓的高容量血液滤过）或使用吸附剂系统再生血浆滤液来清除过量的循环细胞因子。
