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      New Insights Regarding Rationale, Therapeutic Target and Dose of Hemofiltration and Hybrid Therapies in Septic Acute Kidney Injury

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          Abstract

          Mediator removal from tissue (capillary blood compartment, CABC) and transport to the central circulation (central blood compartment, CEBC) must be effective. Effectiveness through a passive mechanism seems unlikely as the surface of CEBC (30 m<sup>2</sup>) is smaller than CABC (300 m<sup>2</sup>) whereby the former will be a limiting factor in passive transport. According to studies, a high exchange volume can induce an 80-fold increase in lymphatic flow. This results in displacement (active transport) of mediators to CEBC. Recent studies have shown that the delivered dose constitutes the mainstay of continuous renal replacement therapy. However, these results are not likely to change the recommendation: 35 ml/kg/h, adjusted for predilution, in septic acute kidney injury (AKI). Recently, studies were focusing on global intensive care unit AKI. In non-septic AKI, those studies show that 20–25 ml/kg/h was optimal. The DO-RE-MI trial underscored the importance of delivery which could be obtained by targeting doses between 5 and 10 ml/kg/h higher than prescribed. Until the IVOIRE trial becomes available, septic AKI should be treated by continuous veno-venous hemofiltration at 35 ml/kg/h. In non-septic AKI, 25 ml/kg/h remains optimal.

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          Most cited references44

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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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            Daily hemodialysis and the outcome of acute renal failure.

            Intermittent hemodialysis is widely used as renal-replacement therapy in patients with acute renal failure, but an adequate dose has not been defined. We performed a prospective study to determine the effect of daily intermittent hemodialysis, as compared with conventional (alternate-day) intermittent hemodialysis, on survival among patients with acute renal failure. A total of 160 patients with acute renal failure were assigned to receive daily or conventional intermittent hemodialysis. Survival was the primary end point of the study. The duration of acute renal failure and the frequency of therapy-related complications were secondary end points. The two study groups were similar with respect to age, sex, cause and severity of acute renal failure, medical or surgical intensive care setting, and the score on the Acute Physiology, Age, and Chronic Health Evaluation. Daily hemodialysis resulted in better control of uremia, fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure (mean [+/-SD], 9+/-2 vs. 16+/-6 days; P=0.001) than did conventional hemodialysis. The mortality rate, according to the intention-to-treat analysis, was 28 percent for daily dialysis and 46 percent for alternate-day dialysis (P=0.01). In a multiple regression analysis, less frequent hemodialysis (on alternate days, as opposed to daily) was an independent risk factor for death. The high mortality rate among critically ill patients with acute renal failure who require renal-replacement therapy is related to both coexisting conditions and uremic damage to other organ systems. Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity.
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              Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: a randomized controlled trial.

              The impact of continuous venovenous hemofiltration on sepsis-induced multiple organ failure severity is controversial. We sought to assess the effect of early application of hemofiltration on the degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock. Prospective, randomized, open, multicenter study setting, 12 French intensive care units. A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult. Patients were randomized to group 1 (HF), who received hemofiltration (25 mL/kg/hr) for a 96-hour period, or group 2 (C) who were managed conventionally. The primary end point was the number, severity, and duration of organ failures during 14 days, as evaluated by the Sepsis-Related Organ Failure Assessment score, on an intention-to-treat analysis. Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers. Because of inclusion stagnation, the trial was discontinued after an interim analysis by which time 76 patients had been randomized. The number and severity of organ failures were significantly higher in the HF group (p 35 mL/kg/hr) on the course of sepsis.
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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
                2012
                March 2012
                15 December 2011
                : 33
                : 1-3
                : 44-51
                Affiliations
                aIntensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, and bIntensive Care Unit, Cliniques de l’Europe-Site St Michel, Brussels, and cDepartment of Anesthesiology and Critical Care Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium; dHaut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France
                Author notes
                *Patrick M. Honoré, MD, Director of Critical Care Nephrology Platform, Intensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, BE–1090 Brussels (Jette) (Belgium), Tel. +32 24 749 097, E-Mail Patrick.Honore@uzbrussel.be
                Article
                333837 Blood Purif 2012;33:44–51
                10.1159/000333837
                22179226
                1273787c-cbd9-4277-a425-1230582ebbc8
                © 2011 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.

                History
                Page count
                Pages: 8
                Categories
                In-Depth Review

                Cardiovascular Medicine,Nephrology
                Hemofiltration,Sepsis,Septic shock,Systemic inflammatory response syndrome,Kidney injury, acute,Tubular apoptosis, acute,Sepsis modulation,Dialysis,Continuous renal replacement therapy

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