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      Emerging Therapies for Extracorporeal Support

      , ,

      Nephron Physiology

      S. Karger AG

      Acute kidney injury, Dialysis, Liver dialysis, Sepsis, Ultrafiltration

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          Abstract

          Dialytic therapies have undergone major technological developments in the last decade and emerging techniques are promoted not only for acute kidney injury, but also for sepsis, acute decompensated heart failure, and acute and acute-on-chronic liver failure. New devices specifically target the pathophysiological mechanisms involved in these conditions. In septic shock and sepsis, high-volume hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and high permeability hemofiltration enhance removal of pro-inflammatory mediators, while in liver failure, Molecular Adsorbents recycling System (MARS®) and Prometheus® favor the elimination of albumin-bound toxins such as bilirubin. In acute decompensated heart failure, simplified ultrafiltration machines are used to reach negative fluid balance in a minimalist setting. In the context of limited resources and growing expansion in the availability of technologies, a critical assessment is required and the use of these devices needs to be put in perspective. This article reviews the mechanisms, advantages and limitations of these techniques along with the current evidence available regarding their influence on major clinical outcomes.

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          Most cited references 15

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          Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock.

          To evaluate the effects of short-term, high-volume hemofiltration (STHVH) on hemodynamic and metabolic status and 28-day survival in patients with refractory septic shock. Prospective, interventional. Intensive care unit (ICU), tertiary institution. Twenty patients with intractable cardiocirculatory failure complicating septic shock, who had failed to respond to conventional therapy. STHVH, followed by conventional continuous venovenous hemofiltration. STHVH consisted of a 4-hr period during which 35 L of ultrafiltrate is removed and neutral fluid balance is maintained. Subsequent conventional continuous venovenous hemofiltration continued for at least 4 days. Cardiac index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery, mixed venous oxygen saturation, arterial pH, and lactate were measured serially. Fluid and inotropic support were managed by protocol. Therapeutic endpoints were as follows during STHVH: a) by 2 hrs, a > or =50% increase in cardiac index; b) by 2 hrs, a > or =25% increase in mixed venous saturation; c) by 4 hrs, an increase in arterial pH to >7.3; d) by 4 hrs, a > or =50% reduction in epinephrine dose. Patients who attained all four goals (11 of 20) were considered hemodynamic "responders"; patients who did not (9 of 20) were considered hemodynamic "nonresponders." There were no differences in baseline hemodynamic, metabolic, and Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Scores between responders and nonresponders. Survival to 28 days was better among responders (9 of 11 patients) than among nonresponders (0 of 9). Factors associated with survival were hemodynamic-metabolic response status, time interval from ICU admission to initiation of STHVH, and body weight. These data suggest that STHVH may be of major therapeutic value in the treatment of intractable cardiocirculatory failure complicating septic shock. Early initiation of therapy and adequate dose may improve hemodynamic and metabolic responses and 28-day survival.
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            A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.

            Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.
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              Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies.

              Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal replacement therapy. Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery. This outcome can be explained by the low efficiency of the procedure. A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period. For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used. In vitro studies indicated that the Gambro HCO 1100 dialyzer was the most efficient of seven tested. Model calculations suggested that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred. FLC concentrations rebounded on successive days unless chemotherapy was effective. Five additional patients with acute renal failure that was caused by cast nephropathy then were treated aggressively, and three became dialysis independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk. Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts. Proof of clinical value now will require larger studies.
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                Author and article information

                Journal
                NEP
                Nephron Physiol
                10.1159/issn.1660-2137
                Nephron Physiology
                S. Karger AG
                978-3-8055-8646-7
                978-3-8055-8647-4
                1660-2137
                2008
                September 2008
                18 September 2008
                : 109
                : 4
                : p85-p91
                Affiliations
                University of California at San Diego, San Diego, Calif., USA
                Article
                142941 Nephron Physiol 2008;109:p85
                10.1159/000142941
                18802380
                © 2008 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: 1, Tables: 1, References: 24, Pages: 1
                Categories
                Paper

                Cardiovascular Medicine, Nephrology

                Acute kidney injury, Dialysis, Liver dialysis, Sepsis, Ultrafiltration

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