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      Changes in Plasma Interleukin-18 by Direct Hemoperfusion with Polymyxin B-Immobilized Fiber in Patients with Septic Shock

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          Background/Aims: Polymyxin B-immobilized fiber (PMX-F) treatment is reported to be safe and effective in patients with severe sepsis and septic shock. The aim of the present study was to determine whether plasma levels of interleukin (IL)-18, which is linked with sepsis, are associated with plasma endotoxin levels and sepsis-related scores and whether PMX-F treatment affects these variables in patients with septic shock. Patients and Methods: Twenty-six patients with septic shock (15 men and 11 women; mean age 56.5 years) and 20 age-matched healthy subjects (12 men and 8 women; mean age 54.0 years) were included in this study. Septic shock patients were divided into 2 groups: a PMX-F treatment group (9 men and 5 women; mean age 57.5 years) and a conventional treatment group (7 men and 5 women; mean age 55.3 years). Standard supportive care was continued without change during PMX-F treatment. Plasma endotoxin, plasma IL-18, and clinical variables were measured before, immediately after the first and second PMX-F treatment, and the following day. Results: The plasma IL-18 levels were significantly higher in septic shock patients (1,320 ± 360 pg/ml) than in healthy volunteers (140 ± 60 pg/ml; p < 0.001). The IL-18 level was significantly correlated with the plasma endotoxin level (p < 0.001), the Acute Physiology and Chronic Health Evaluation II score (p < 0.01), the Sepsis Severity Score (p < 0.01), the number of failed organs (p < 0.01), and the Goris score (p < 0.01). PMX-F treatment reduced the plasma endotoxin and IL-18 levels significantly after the first treatment (p < 0.05), after the second treatment (p < 0.01), and on the following day (p < 0.001). However, these variables did not change significantly during conventional treatment. Conclusions: IL-18 may be associated with the severity of septic shock, and PMX-F treatment is effective in reducing the IL-18 level in patients with septic shock.

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          Most cited references 12

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          American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference

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            Urinary interleukin-18 is a marker of human acute tubular necrosis.

            Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.
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              Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin).

              Toray Industries Inc. has developed an endotoxin removal cartridge (Toraymyxin) composed of a polymyxin B immobilized, fibrous adsorbent. Toraymyxin has been listed as a blood purification medical device for endotoxin removal to be reimbursed by the Japanese national health insurance since 1994. Toraymyxin can be applied to patients with endotoxemia or suspected gram-negative infection, which fulfilll the conditions of Systemic Inflammatory Response Syndrome (SIRS) and have septic shock demanding vasopressor infusion. Since 1994, over 30,000 patients have received this treatment. The safety of this device has been confirmed and improvement of hemodynamic dysfunction has been shown to be a major benefit. Infection resulting from an acute abdominal condition requiring surgery has been shown to be one of the good indications for Toraymyxin. Further studies are now ongoing to establish Toraymyxin treatment as one of the options to treat sepsis and septic shock patients and to clarify the mechanisms involved in this therapy.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                December 2005
                19 December 2005
                : 23
                : 6
                : 417-420
                aDepartment of Medicine, Shinmatsudo Central General Hospital, Chiba; bArtificial Organs Department, Toray Medical Co., Ltd., Tokyo; cDepartment of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, and dDepartment of Medicine, Koto Hospital, Tokyo, Japan
                88016 Blood Purif 2005;23:417–420
                © 2005 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
                Tables: 4, References: 20, Pages: 4
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/88016
                Original Paper


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