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      Cytokine removal in human septic shock: Where are we and where are we going?

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          Abstract

          Although improving, the mortality from septic shock still remains high despite increased international awareness. As a consequence, much effort has focused on alternative treatment strategies in an effort to improve outcomes. The application of blood purification therapies to improve immune homeostasis has been suggested as one such method, but these approaches, such as high-volume continuous haemofiltration or cytokine and/or endotoxin removal, have enjoyed little success to date. More recently, the use of sorbent technologies has attracted much attention. These adsorbers are highly effective at removing inflammatory mediators, in particular, cytokines, from the bloodstream. This narrative review is the executive summary of meetings held throughout the 6th International Fluid Academy Days in Antwerp, Belgium (Nov 23–25, 2017), focusing on the current understanding regarding the use of such adsorbers in humans with septic shock. We followed a modified Delphi approach involving a combination of evidence appraisal together with expert opinion in order to achieve recommendations for practice and, importantly, future research.

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          Most cited references 63

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          Benchmarking the incidence and mortality of severe sepsis in the United States.

          In 1992, the first consensus definition of severe sepsis was published. Subsequent epidemiologic estimates were collected using administrative data, but ongoing discrepancies in the definition of severe sepsis produced large differences in estimates. We seek to describe the variations in incidence and mortality of severe sepsis in the United States using four methods of database abstraction. We hypothesized that different methodologies of capturing cases of severe sepsis would result in disparate estimates of incidence and mortality. Using a nationally representative sample, four previously published methods (Angus et al, Martin et al, Dombrovskiy et al, and Wang et al) were used to gather cases of severe sepsis over a 6-year period (2004-2009). In addition, the use of new International Statistical Classification of Diseases, 9th Edition (ICD-9), sepsis codes was compared with previous methods. Annual national incidence and in-hospital mortality of severe sepsis. The average annual incidence varied by as much as 3.5-fold depending on method used and ranged from 894,013 (300/100,000 population) to 3,110,630 (1,031/100,000) using the methods of Dombrovskiy et al and Wang et al, respectively. Average annual increase in the incidence of severe sepsis was similar (13.0% to 13.3%) across all methods. In-hospital mortality ranged from 14.7% to 29.9% using abstraction methods of Wang et al and Dombrovskiy et al. Using all methods, there was a decrease in in-hospital mortality across the 6-year period (35.2% to 25.6% [Dombrovskiy et al] and 17.8% to 12.1% [Wang et al]). Use of ICD-9 sepsis codes more than doubled over the 6-year period (158,722 - 489,632 [995.92 severe sepsis], 131,719 - 303,615 [785.52 septic shock]). There is substantial variability in incidence and mortality of severe sepsis depending on the method of database abstraction used. A uniform, consistent method is needed for use in national registries to facilitate accurate assessment of clinical interventions and outcome comparisons between hospitals and regions.
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            Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial

            Purpose To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. Method Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. Results Primary outcome: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5 % in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95 % CI 0.8583–2.935). Secondary endpoints: mortality rate at day 90 was 33.6 % in PMX-HP versus 24 % in conventional groups, p = 0.10 (OR 1.6128, 95 % CI 0.9067–2.8685); reduction in SOFA score from day 0 to day 7 was −5 (−11 to 6) in PMX-HP versus −5 (−11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. Conclusion This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3751-z) contains supplementary material, which is available to authorized users.
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              Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony.

              Septic syndromes represent a major although largely underrecognized healthcare problem worldwide, accounting for thousands of deaths every year. It is now agreed that sepsis deeply perturbs immune homeostasis by inducing an initial tremendous systemic inflammatory response which is accompanied by an antiinflammatory process, acting as negative feedback. This compensatory inhibitory response secondly becomes deleterious as nearly all immune functions are compromised. These alterations might be directly responsible for worsening outcome, as they may play a major role in the decreased resistance to nosocomial infections in patients who survived initial resuscitation. Consequently, immunostimulatory therapies may now be assessed for the treatment of sepsis. This review focuses on immune dysfunctions described in septic patients and on their potential use as markers on a routine standardized basis for prediction of adverse outcome or of occurrence of secondary nosocomial infections. This constitutes a prerequisite to a staging system for individualized treatment for these hitherto deadly syndromes.
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                Author and article information

                Contributors
                Patrick.Honore@CHU-Brugmann.be
                Eric.Hoste@UGent.be
                zsoltmolna@gmail.com
                Rita.Jacobs@uzbrussel.be
                olivier.joannes-boyau@chu-bordeaux.fr
                Manu.Malbrain@uzbrussel.be
                luiforni@nhs.net
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                14 May 2019
                14 May 2019
                2019
                : 9
                Affiliations
                [1 ]ISNI 0000 0004 0469 8354, GRID grid.411371.1, Intensive Care Department, , CHU Brugmann University Hospital, ; 4, Place Arthur Van Gehuchtenplein, 1020 Brussels, Belgium
                [2 ]ISNI 0000 0004 0626 3303, GRID grid.410566.0, Intensive Care Department, , Ghent University Hospital, ; Ghent, Belgium
                [3 ]ISNI 0000 0001 1016 9625, GRID grid.9008.1, Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, , University of Szeged, ; Szeged, Hungary
                [4 ]ISNI 0000 0004 0626 3362, GRID grid.411326.3, Intensive Care Department, , University Hospital Brussels (UZB), ; Jette, Belgium
                [5 ]ISNI 0000 0004 0593 7118, GRID grid.42399.35, Département d’Anesthésie-Réanimation SUD, , CHU Bordeaux, ; 33000 Bordeaux, France
                [6 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Faculty of Medicine and Pharmacy, , Vrije Universiteit Brussel (VUB), ; Brussels, Belgium
                [7 ]ISNI 0000 0001 0372 6120, GRID grid.412946.c, Department of Critical Care, , Royal Surrey County Hospital, NHS Foundation Trust, ; Guildford, UK
                [8 ]ISNI 0000 0004 0407 4824, GRID grid.5475.3, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, , University of Surrey, ; Guildford, UK
                Article
                530
                10.1186/s13613-019-0530-y
                6517449
                31089920
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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