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      Combined Extracorporeal Therapy for Severe Sepsis in Patients after Cardiac Surgery

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          Abstract

          Introduction: Sepsis still represents an obstacle in modern medicine. The aim of this study was to evaluate the effectiveness and safety of the combined use of lipopolysaccharide adsorption and haemodialysis (HD) with high cut-off haemofilters as part of the complex intensive care of patients with severe sepsis after cardiac surgery. Methods: The study group included 26 patients, 57 (48-62) years of age, with severe sepsis. The inclusion criteria were clinical signs of severe sepsis (systemic inflammatory response syndrome + infection site + failure of two or more organs) together with endotoxin activity assay (EAA) ≥0.6 and procalcitonin (PCT) levels ≥2 ng/ml. Antimicrobial therapy was initiated in the first hour after the diagnosis of severe sepsis and extracorporeal therapy was initiated within 24 h. All of the patients in the study group received standard therapy. Additionally, they received treatment consisting of two LPS adsorption procedures and HD procedures with high cut-off haemofilters in a single circuit. For the control group, 30 comparable patients, 57 (51-61) years of age, were selected and received only standard therapy. Results: After the last HD procedure within the extracorporeal therapy, we noted an increase in the mean arterial pressure from 76 to 90 mm Hg, p < 0.01, and oxygenation index (from 226 to 291, p < 0.02), in addition to decreases in the LPS concentration according to EAA (from 0.73 to 0.59, p < 0.01) and the Limulus amebocyte lysate test (from 1.44 to 0.36 IU/ml, p < 0.01); PCT falls from 8.19 to 2.44 ng/ml, p < 0.01, and sepsis-related organ failure assessment scores decreases from 13 to 10, p = 0.007. When we compared the data between the study group the day after the procedures and the control group 3 days after the start of intensive care, we discovered that there were statistically significant differences in mean arterial pressure (90 vs. 81 mm Hg, p = 0.0004), oxygenation index (291 vs. 229, p = 0.01), and EAA levels (0.59 vs. 0.67, p = 0.05). Differences in the PCT were not significant (2.44 vs. 3.41, p = 0.15). The 28-day survival rate in the study group was higher than that in the control group (65.4 vs. 33.3%, p = 0.03). Conclusion: The combined use of LPS adsorption and HD with high cut-off haemofilters in conjunction with standard therapy is a safe, effective method for treating patients who have severe sepsis.

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          Most cited references26

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          Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.

          A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (>or=0.40 endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.
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            Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis.

            Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.
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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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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2014
                March 2014
                05 February 2014
                : 37
                : 1
                : 39-46
                Affiliations
                Bakoulev Scientific Centre for Cardiovascular Surgery, Moscow, Russia
                Author notes
                *Michail Yaroustovsky, Bakoulev Scientific Centre for Cardiovascular Surgery, 135, Roublevskoe shosse, Moscow 121552 (Russia), E-Mail mbyar@yandex.ru
                Article
                357015 Blood Purif 2014;37:39-46
                10.1159/000357015
                24503765
                0486fe12-55c3-4a00-9ec1-9f9bc4c05258
                © 2014 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
                : 02 August 2013
                : 05 November 2013
                Page count
                Figures: 2, Tables: 3, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                High cut-off haemofilters,Cardiac surgery,Severe sepsis,Endotoxin,LPS adsorption,Haemodialysis

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