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      Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure

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          Abstract

          Introduction

          Cytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Extracorporeal liver support systems may exert beneficial effects in ACLF via removal of cytokines. At present, two systems are commercially available, the Molecular Adsorbent Recirculating System (MARS™) and Fractionated Plasma Separation, Adsorption and Dialysis (Prometheus™). The aim of this study was to compare the effects of MARS and Prometheus treatments on serum cytokine levels and their clearances.

          Methods

          Eight patients with ACLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Thirty-four treatments (17 MARS, 17 Prometheus) were available for analysis. Serum cytokines were measured before and after each treatment, and cytokine clearance was calculated from paired arterial and venous samples and effective plasma flow one hour after the start of treatment.

          Results

          Baseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and soluble TNF-α receptor 1 were significantly elevated in patients with ACLF. Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus. In MARS treatments, IL-10 was cleared from plasma more efficiently than IL-6. Clearance of IL-10 was higher in Prometheus than in MARS treatments.

          Conclusion

          Cytokines are cleared from plasma by both MARS and Prometheus, but neither system is able to change serum cytokine levels. This discrepancy is probably due to a high rate of cytokine production in patients with ACLF.

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          Most cited references40

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          American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.

          (1992)
          To define the terms "sepsis" and "organ failure" in a precise manner. Review of the medical literature and the use of expert testimony at a consensus conference. American College of Chest Physicians (ACCP) headquarters in Northbrook, IL. Leadership members of ACCP/Society of Critical Care Medicine (SCCM). An ACCP/SCCM Consensus Conference was held in August of 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic variables by which a patient could be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods were recommended when dealing with septic patients as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.
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            Transection of the oesophagus for bleeding oesophageal varices.

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              Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study.

              The pathophysiological basis of acute-on-chronic liver failure (ACLF) is unclear but systemic inflammatory response is thought to be important. In patients with ACLF, the molecular adsorbents recirculating system (MARS) improves individual organ function, but the effect of MARS on the proposed mediators of systemic inflammatory response is unclear. The present study was designed to determine the effect of MARS on the cytokine profile, oxidative stress, nitric oxide, and ammonia. A total of 18 patients with alcohol-related ACLF due to inflammation-related precipitants were randomized to receive standard medical therapy (SMT) alone, or with MARS therapy over 7 days. Plasma cytokines, malondialdehyde (MDA), free radical production, nitrate / nitrite (NOx), and ammonia were measured. Encephalopathy improved significantly with MARS (P < .01), but not with SMT. Mean arterial pressure and renal function remained unchanged. No significant change of plasma cytokines and ammonia levels were observed in either group. Plasma MDA levels did not change either. There was a fall in NOx (P < .05) with MARS, but not with SMT. In conclusion, in inflammation-related ACLF patients, albumin dialysis using MARS results in improvement of encephalopathy, independent of changes of ammonia or cytokines, without improving blood pressure or renal function. These results should temper the liberal use of MARS until further data is available.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                2006
                7 December 2006
                : 10
                : 6
                : R169
                Affiliations
                [1 ]Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
                [2 ]Department of Internal Medicine, Division of Nephrology and Hemodialysis, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
                [3 ]Department of Radiology, Division of Nuclear Medicine, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz, Austria
                [4 ]Department of Medical Physics, AGH University of Science and Technology, Mickiewicza Ave, PL-30 059 Krakow, Poland
                [5 ]Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria
                Article
                cc5119
                10.1186/cc5119
                1794485
                17156425
                63883f62-5b40-42ac-833a-6d99227de555
                Copyright © 2006 Stadlbauer et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 October 2006
                : 6 November 2006
                : 15 November 2006
                : 7 December 2006
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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