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      Continuous Renal Replacement Technology: From Adaptive Technology and Early Dedicated Machines towards Flexible Multipurpose Machine Platforms

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          Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

          Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).
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            The pathogenesis of septic acute renal failure.

            Acute renal failure is a serious condition that affects as many as 20% of ICU patients. The most common causes of acute renal failure in the ICU patient are severe sepsis and septic shock. The mortality of acute renal failure in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly the result of our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. Accordingly, a review of our current understanding of the pathogenesis of septic acute renal failure is timely and relevant. Throughout the past half century, acute renal failure of acute illness has essentially been considered a hemodynamic disease caused by kidney ischemia, a view derived by findings in animal models. Unfortunately most such models are greatly deficient in that they do not reproduce the high cardiac output, low systemic vascular resistance state typically seen during human sepsis. Furthermore, most models inducing so-called acute tubular necrosis are based on ischemia-reperfusion (renal artery clamping), an event with little relevance to human sepsis. Recent research highlights a new possible and emerging concept for the pathogenesis of septic acute renal failure: acute apoptosis. This concepts fits well with the typical paucity of histologic changes seen in so-called acute tubular necrosis and with growing evidence of a role for apoptosis in organ injury during sepsis and inflammation in general. Furthermore, the authors present evidence that some potential treatments recently shown to affect the mortality of critically ill patients, (activated protein C, intensive insulin treatment, and low-volume mechanical ventilation) might have antiapoptotic activity. This review suggests that, on the evidence available, septic acute renal failure is more likely to be an immune or toxic state rather than simply a hemodynamic condition. The authors speculate that future insights into its pathogenesis might lead to a paradigm shift away from the concept of acute tubular necrosis, which has never been convincingly shown in sepsis, to that of acute tubular apoptosis.
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              Coupled Plasma Filtration Adsorption: Rationale, Technical Development and Early Clinical Experience

              The 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.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2004
                May 2004
                09 July 2004
                : 22
                : 3
                : 269-276
                Affiliations
                Departments of aNephrology and bIntensive Care, St. Bortolo Hospital, Vicenza, Italy; cDepartment of Intensive Care, Austin Hospital, Heidelberg, Vic., Australia
                Article
                78431 Blood Purif 2004;22:269–276
                10.1159/000078431
                15148455
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 10, References: 19, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/78431
                Categories
                Review

                Cardiovascular Medicine, Nephrology

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