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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Cytokine Removal in Septic Patients with Continuous Venovenous Hemofiltration

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          Abstract

          Despite the progress that has been made in intensive care medicine, multiple organ failure is still associated with high mortality. Apart from the prevention of infectious complications, numerous efforts are being made to improve the treatment of sepsis through adequate antibiotic therapy, the development of new respirator therapies, better control of the hemodynamic situation, and adequate renal replacement therapy. Some authors advocate continuous renal replacement therapy not only for acute renal failure but also for the elimination of inflammatory molecules such as cytokines. Continuous renal replacement therapy improves the cardiovascular hemodynamics in patients with multiple organ failure. Therapeutic options such as volume control, clearance of uremic toxins, correction of acid base disturbances and temperature control are improved. Suitable renal replacement therapy improves not only cardiovascular hemodynamics but also patient survival. In current practice, continuous renal replacement therapy is not used to eliminate mediators such as cytokines. In patients with multiple organ failure and compromised cardiovascular hemodynamics, renal replacement therapy should be carried out as early as possible. In the following review, experimental and clinical findings concerning mediator elimination by continuous and intermittent renal replacement therapy are summarized.

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          Most cited references9

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          Long-term results of overlapping anterior anal-sphincter repair for obstetric trauma.

          Anterior structural damage to the anal sphincter occurs in up to a third of women at first vaginal delivery, and of these a third have new bowel symptoms. The standard treatment for such structural damage is anterior overlapping anal-sphincter repair. We aimed to assess the long-term results of this operation. We assessed the long-term results in 55 consecutive patients who had had repair a minimum of 5 years (median 77 months [range 60-96]) previously. Questionnaire and telephone interview assessed current bowel function and continence, restriction in activities related to bowel control, and overall satisfaction with the results of surgery. 42 of these patients had been continent of solid and liquid stool at a median of 15 months after the repair. We were able to contact 47 (86%) of the 55 patients. One of these patients had required a proctectomy and end ileostomy for Crohn's disease. Of the remaining 46 patients, 27 reported improved bowel control without the need for further surgery, and 23 rated their symptom improvement as 50% or greater. Seven patients had undergone further surgery for incontinence and one patient had not had a covering stoma closed. Thus, the long-term functional outcome of the sphincter repair alone could be assessed in 38 patients. Of these patients, none was fully continent to both stool and flatus; only four were totally continent to solid and liquid stool; six had no faecal urgency; and eight had no passive soiling. Of the 38 patients, 20 still wore a pad for incontinence and 25 reported lifestyle restriction. 14 reported the onset of a new evacuation disorder after sphincter repair. 23 of the 46 patients contacted had a successful long-term outcome (defined as no further surgery and urge faecal incontinence monthly or less). The results of overlapping sphincter repair for obstetric anal-sphincter damage seem to deteriorate with time. Preoperative counselling should emphasise that although most patients will improve after the procedure, continence is rarely perfect, many have residual symptoms, and some may develop new evacuation disorders.
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            Elevated serum levels of the type I and type II receptors for tumor necrosis factor-alpha as predictive factors for ARF in patients with septic shock.

            Acute renal failure (ARF), a common and serious complication in patients with septic shock, has high mortality. Recent data suggest that proinflammatory cytokines may contribute to sepsis-associated ARF. To examine the role of proinflammatory cytokines, we evaluated 537 patients enrolled in the placebo arm of the Norasept II study, of whom 112 patients (20%) developed ARF. By univariate analysis, the following factors were significantly associated with the development of ARF: male sex, younger age, increased heart rate, higher Acute Physiology and Chronic Health Evaluation II score, oliguria, increased blood urea nitrogen level, increased serum creatinine (Scr) level, decreased arterial pH, and increased serum potassium level. Although there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 between patients with and without ARF, elevated serum levels of the two soluble TNF-alpha receptors (S-TNF-RI and S-TNF-RII) were strongly associated with the development of ARF (S-TNF-RI, 25 +/- 16 versus 18 +/- 13 ng/mL; P = 0.00006; S-TNF-RII, 25 +/- 21 versus 18 +/- 17 ng/mL; P = 0.0007). Using forward stepwise regression analysis, elevated S-TNF-R level remained an independent predictor for ARF, even when we limited our analysis to patients with Scr levels of 1.4 mg/dL or less (< or =124 micromol/L) at study entry, suggesting that decreased renal clearance of S-TNF-R alone cannot account for this association. Elevated S-TNF-R level also was an independent predictor of mortality among patients developing ARF. S-TNF-R level is an independent predictor for the development of ARF and mortality. We speculate that elevated S-TNF-R levels may reflect a more intense inflammatory response. Copyright 2003 by the National Kidney Foundation, Inc.
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              Effects of filter pore size on efficacy of continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine.

              To evaluate the effect of hemofilter pore size on the efficacy of continuous arteriovenous hemofiltration (CAVH) in improving morbidity and mortality in an immature swine model of Staphylococcus aureus-induced septicemia. Prospective, randomized study with age-matched controls. Biomedical research facility. Fourteen 4 to 8-wk-old, weaned Poland-China swine, weighing 5 to 10 kg. Spontaneously breathing, ketamine-sedated swine (4 to 8 wks of age) were given an intravenous lethal dose of live S. aureus. Animals were then filtered with either a 50-kilodalton (kD) pore size filter (control) or a 100-kD pore size filter (experimental). No animals received antibiotics. Physiologic, biochemical, and hematologic parameters were measured in all animals every 1 to 3 hrs. Animals were monitored continuously and survival time (hr) was recorded (permanent survival = 168 hrs/7 days). Animals filtered with the 100-kD filter survived significantly longer than control animals (103 +/- 18 [SEM] vs. 56 +/- 9 hrs). The 100-kD-filtered group had one permanent survivor (168 hrs). Protein concentration of the ultrafiltrate obtained from the 100-kD-filtered animals was eight-fold higher than control ultrafiltrate. The protein removed did not contain a high percentage of albumin (as determined by autoanalyzer methods). No significant differences were seen in any of the other measured parameters. CAVH significantly improved survival in swine with S. aureus-induced sepsis. The superior performance of the 100-kD filter vs. the 50-kD filter suggests that higher molecular weight mediators that are not removed efficiently by the 50-kD filter may be responsible for the morbidity and mortality seen in this model of sepsis. These mediators may be removed in greater proportion by our customized (100-kD pore size) filter.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                978-3-8055-7600-0
                978-3-318-00991-0
                1420-4096
                1423-0143
                2003
                2003
                05 June 2003
                : 26
                : 2
                : 128-134
                Affiliations
                aDepartment of Medicine III, Solingen General Hospital, University of Cologne, Solingen and bDepartment of Nephrology and Rheumatology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
                Article
                70996 Kidney Blood Press Res 2003;26:128–134
                10.1159/000070996
                12771539
                c6eb9bc4-7de8-4d77-bc80-0a268e86a33f
                © 2003 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
                Tables: 2, References: 36, Pages: 7
                Categories
                Paper

                Cardiovascular Medicine,Nephrology
                Continuous venovenous hemofiltration,Cytokine removal,Sepsis

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