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Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis

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      BackgroundFree hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.MethodsThis is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.ResultsSimilar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).ConclusionsOld RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.Trial RegistrationClinicalTrials.gov NCT01584999

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      Most cited references 48

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      The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.

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        2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

        In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the SCCM, The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). The conference was attended by 29 participants from Europe and North America. In advance of the conference, five subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The subgroups corresponded electronically before the conference and met in person during the conference. A spokesperson for each group presented the deliberation of each group to all conference participants during a plenary session. A writing committee was formed at the conference and developed the current article based on executive summary documents generated by each group and the plenary group presentations. The present article serves as the final report of the 2001 International Sepsis Definitions Conference. This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence exists to support a change to the definitions. This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research.
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          A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

          To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.
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            Author and article information

            Affiliations
            [1 ]Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Torrette di Ancona, Italy
            [2 ]Anesthesia and Intensive Care Unit, Azienda Ospedaliera Universitaria “Ospedali Riuniti”, Torrette di Ancona, Italy
            [3 ]Department of Clinical and Molecular Sciences, Clinica Medica, Università Politecnica delle Marche, Torrette di Ancona, Italy
            [4 ]Immunohematology and Transfusional Medicine, AOU Ospedali Riuniti, Torrette di Ancona, Italy
            [5 ]Department of Translational Physiology, Academic Medical Center, Amsterdam, The Netherlands
            Erasmus Medical Centre, NETHERLANDS
            Author notes

            Competing Interests: CI is the inventor of sidestream dark field imaging technology and holds shares in MicroVision Medical and was a consultant for this company more than four years ago but has had no further contact with the company since then. He has no other competing interests in this field other than his commitment to promoting the importance of the microcirculation during patient care; and there are no other relationships or activities that could appear to have influenced the submitted work. The other authors have no competing interests to declare.

            Conceived and designed the experiments: ED CI AD. Performed the experiments: ED EA CS AC NM SP TP DS RB. Analyzed the data: ED MML AG. Contributed reagents/materials/analysis tools: EA RR PP AD. Wrote the paper: ED CI AD.

            Contributors
            Role: Academic Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            1932-6203
            1 May 2015
            2015
            : 10
            : 5
            25932999
            4416810
            10.1371/journal.pone.0122655
            PONE-D-14-45290
            (Academic Editor)

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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            The authors received no specific funding for this work.
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            Research Article
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            All relevant data are within the paper and its Supporting Information files.

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