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      Organ dysfunction as a new standard for defining sepsis

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          Abstract

          Despite advances in intensive care and the widespread use of standardized care included in the Surviving Sepsis Campaign Guidelines, sepsis remains a leading cause of death, and the prevalence of sepsis increases concurrent with the aging process. The diagnosis of sepsis was originally based on the evidence of persistent bacteremia (septicemia) but was modified in 1992 to incorporate systemic inflammatory response syndrome (SIRS). Since then, SIRS has become the gold standard for the diagnosis of sepsis. In 2016, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine published a new clinical definition of sepsis that is called Sepsis-3. In contrast to previous definitions, Sepsis-3 is based on organ dysfunctions and uses a sequential organ failure (SOFA) score as an index. Thus, patients diagnosed with respect to Sepsis-3 will inevitably represent a different population than those previously diagnosed. We assume that this drastic change in clinical definition will affect not only clinical practice but also the viewpoint and focus of basic research. This review intends to summarize the pathophysiology of sepsis and organ dysfunction and discusses potential directions for future research.

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          Most cited references23

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          HMG-1 as a late mediator of endotoxin lethality in mice.

          Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
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            Systemic inflammatory response syndrome criteria in defining severe sepsis.

            The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach.
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              The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis.

              The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations. A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit, emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008. A total of 15,022 subjects. Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 yrs (95% confidence interval, 2.5-8.4). The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.
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                Author and article information

                Contributors
                fujishim@keio.jp
                Journal
                Inflamm Regen
                Inflamm Regen
                Inflammation and Regeneration
                BioMed Central (London )
                1880-9693
                1880-8190
                15 November 2016
                15 November 2016
                2016
                : 36
                : 24
                Affiliations
                GRID grid.26091.3c, ISNI 0000000419369959, Center for General Medicine Education, , Keio University School of Medicine, ; Tokyo, Japan
                Article
                29
                10.1186/s41232-016-0029-y
                5725936
                29259674
                92c0bd64-87b3-47f3-86c6-bc2fe131fcdc
                © The Author(s) 2016

                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. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 August 2016
                : 1 November 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: 26462767
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                sepsis-3,sequential organ failure assessment score,acute respiratory distress syndrome,acute kidney injury,disseminated intravascular coagulation

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