1,720,976 research outputs found
Future technology for continuous renal replacement therapies
No full textCritically ill patients are increasingly treated with continuous hemofiltration and derived techniques, now grouped under the term of continuous renal replacement therapy (CRRT), CRRT can provide adequate blood purification and correction of electrolyte derangements, They also seem to prevent further injury to the patient by maintaining a stable level of homeostasis, Recently, newer indications have been proposed for CRRT, including the treatment of neonates, patients with heart disease, and septic patients, It has been hypothesized that continuous therapies might contribute to the removal of noxious substances in the middle molecular-weight range, such as cytokines or autocoids, According to these new indications, technical developments are making available new forms of treatment, new materials, and specially designed machines. (C) 1996 by the National Kidney Foundation, Inc
Endotoxin and cytokine removal in sepsis
No full textSespis, the leading cause of mortality in intensive care units, is a complex series of interrelated effects caused by the overproduction of multiple mediators and their unrestrained biological activity. Both proinflammatory and antiinflammatory mediators participate in the high complexity of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as therapeutic options and as tools for blood purification in sepsis. Along these lines and in order to achieve higher clearances and mass removal rates, we studied the effects of plasmafiltration coupled with adsorption and provided in vitro and in vivo evidence that adsoprtion of multiple cytokines, activated complement components, and lipid mediators such as the platelet-activating factor occurs. We also showed that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics. reduced norepinephrine dose, and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma. as a modular device to conventional hemofiltration, may pave the way to innovative approaches in the extracorporeal treatment of septic patients
Coupled plasma filtration adsorption: Rationale, technical development and early clinical experience
No full textThe adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications. Copyright (C) 2003 S. Karger AG, Basel
Relevance of platelet-activating factor in inflammation and sepsis: Mechanisms and kinetics of removal in extracorporeal treatments
No full textSepsis 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 tie, 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. (C) 1997 by the National Kidney Foundation, Inc
Diffusion eliminates immunosuppressor activities in sepsis patients treated with coupled plasma filtration and adsorption (CPFA)
No full textAn overview of haemodialysis and oxidant stress
No full textToday's patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented
Coupled plasma filtration adsorption: Rationale, technical development and early clinical experience
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