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      The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

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          Abstract

          Background

          Severe traumatic injury continues to present challenges to healthcare systems around the world, and post-traumatic bleeding remains a leading cause of potentially preventable death among injured patients. Now in its fifth edition, this document aims to provide guidance on the management of major bleeding and coagulopathy following traumatic injury and encourages adaptation of the guiding principles described here to individual institutional circumstances and resources.

          Methods

          The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004, and the current author group included representatives of six relevant European professional societies. The group applied a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were re-examined and revised based on scientific evidence that has emerged since the previous edition and observed shifts in clinical practice. New recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated.

          Results

          Advances in our understanding of the pathophysiology of post-traumatic coagulopathy have supported improved management strategies, including evidence that early, individualised goal-directed treatment improves the outcome of severely injured patients. The overall organisation of the current guideline has been designed to reflect the clinical decision-making process along the patient pathway in an approximate temporal sequence. Recommendations are grouped behind the rationale for key decision points, which are patient- or problem-oriented rather than related to specific treatment modalities. While these recommendations provide guidance for the diagnosis and treatment of major bleeding and coagulopathy, emerging evidence supports the author group’s belief that the greatest outcome improvement can be achieved through education and the establishment of and adherence to local clinical management algorithms.

          Conclusions

          A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. If incorporated into local practice, these clinical practice guidelines have the potential to ensure a uniform standard of care across Europe and beyond and better outcomes for the severely bleeding trauma patient.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2347-3) contains supplementary material, which is available to authorized users.

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          Most cited references844

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          Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

          Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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            A national evaluation of the effect of trauma-center care on mortality.

            Hospitals have difficulty justifying the expense of maintaining trauma centers without strong evidence of their effectiveness. To address this gap, we examined differences in mortality between level 1 trauma centers and hospitals without a trauma center (non-trauma centers). Mortality outcomes were compared among patients treated in 18 hospitals with a level 1 trauma center and 51 hospitals non-trauma centers located in 14 states. Patients 18 to 84 years old with a moderate-to-severe injury were eligible. Complete data were obtained for 1104 patients who died in the hospital and 4087 patients who were discharged alive. We used propensity-score weighting to adjust for observable differences between patients treated at trauma centers and those treated at non-trauma centers. After adjustment for differences in the case mix, the in-hospital mortality rate was significantly lower at trauma centers than at non-trauma centers (7.6 percent vs. 9.5 percent; relative risk, 0.80; 95 percent confidence interval, 0.66 to 0.98), as was the one-year mortality rate (10.4 percent vs. 13.8 percent; relative risk, 0.75; 95 percent confidence interval, 0.60 to 0.95). The effects of treatment at a trauma center varied according to the severity of injury, with evidence to suggest that differences in mortality rates were primarily confined to patients with more severe injuries. Our findings show that the risk of death is significantly lower when care is provided in a trauma center than in a non-trauma center and argue for continued efforts at regionalization. Copyright 2006 Massachusetts Medical Society.
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              Transfusion strategies for acute upper gastrointestinal bleeding.

              The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).
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                Author and article information

                Contributors
                donat.spahn@usz.ch
                BouillonB@kliniken-koeln.de
                cernyvla1960@gmail.com
                jacques.duranteau@bct.aphp.fr
                Danielafilipescu@b.astral.ro
                Beverley.Hunt@gstt.nhs.uk
                sbcrdi@guest.arnes.si
                marc.maegele@t-online.de
                4doctornardi@gmail.com
                louis.riddez@karolinska.se
                marc.samama@htd.aphp.fr
                jlvincen@ulb.ac.be
                RRossaint@ukaachen.de
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                27 March 2019
                27 March 2019
                2019
                : 23
                : 98
                Affiliations
                [1 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Institute of Anaesthesiology, , University of Zurich and University Hospital Zurich, ; Raemistrasse 100, CH-8091 Zurich, Switzerland
                [2 ]ISNI 0000 0000 9024 6397, GRID grid.412581.b, Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Centre (CMMC), , University of Witten/Herdecke, ; Ostmerheimer Strasse 200, D-51109 Cologne, Germany
                [3 ]ISNI 0000 0001 1379 0994, GRID grid.424917.d, Department of Anaesthesiology, Perioperative Medicine and Intensive Care, , J.E. Purkinje University, Masaryk Hospital, ; Usti nad Labem, Socialni pece 3316/12A, CZ-40113 Usti nad Labem, Czech Republic
                [4 ]ISNI 0000 0004 0609 2284, GRID grid.412539.8, Centre for Research and Development, , University Hospital Hradec Kralove, ; Hradec Kralove, Czech Republic, Sokolska 581, CZ-50005 Hradec Kralove, Czech Republic
                [5 ]ISNI 0000 0004 1937 116X, GRID grid.4491.8, Department of Anaesthesiology and Intensive Care Medicine, Faculty of Medicine in Hradec Kralove, , Charles University, ; Simkova 870, CZ-50003 Hradec Kralove, Czech Republic
                [6 ]ISNI 0000 0004 1936 8200, GRID grid.55602.34, Department of Anaesthesia, Pain Management and Perioperative Medicine, QE II Health Sciences Centre, , Dalhousie University, ; Halifax, 10 West Victoria, 1276 South Park St, Halifax, NS B3H 2Y9 Canada
                [7 ]ISNI 0000 0001 2171 2558, GRID grid.5842.b, Department of Anaesthesia and Intensive Care, , Hôpitaux Universitaires Paris Sud, University of Paris XI, Faculté de Médecine Paris-Sud, ; 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre Cedex, France
                [8 ]Department of Cardiac Anaesthesia and Intensive Care, C. C. Iliescu Emergency Institute of Cardiovascular Diseases, Sos Fundeni 256-258, RO-022328 Bucharest, Romania
                [9 ]GRID grid.420545.2, King’s College and Departments of Haematology and Pathology, Guy’s and St Thomas’ NHS Foundation Trust, ; Westminster Bridge Road, London, SE1 7EH UK
                [10 ]ISNI 0000 0004 0621 9740, GRID grid.415428.e, Department of Traumatology, , General and Teaching Hospital Celje, Medical Faculty Ljubljana University, ; SI-3000 Celje, Slovenia
                [11 ]ISNI 0000 0000 9024 6397, GRID grid.412581.b, Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Centre (CMMC), Institute for Research in Operative Medicine (IFOM), , University of Witten/Herdecke, ; Ostmerheimer Strasse 200, D-51109 Cologne, Germany
                [12 ]GRID grid.414614.2, Department of Anaesthesia and ICU, AUSL della Romagna, , Infermi Hospital Rimini, ; Viale Settembrini, 2, I-47924 Rimini, Italy
                [13 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Department of Surgery and Trauma, , Karolinska University Hospital, ; S-171 76 Solna, Sweden
                [14 ]ISNI 0000 0001 2191 1995, GRID grid.411394.a, Hotel-Dieu University Hospital, ; 1, place du Parvis de Notre-Dame, F-75181 Paris Cedex 04, France
                [15 ]Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070 Brussels, Belgium
                [16 ]ISNI 0000 0001 0728 696X, GRID grid.1957.a, Department of Anaesthesiology, , University Hospital Aachen, RWTH Aachen University, ; Pauwelsstrasse 30, D-52074 Aachen, Germany
                Author information
                http://orcid.org/0000-0001-7587-1693
                Article
                2347
                10.1186/s13054-019-2347-3
                6436241
                30917843
                81f16ab6-f419-4a7b-9026-cc54851048de
                © 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. 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 December 2018
                : 6 February 2019
                Funding
                Funded by: CSL Behring GmbH
                Award ID: N/A
                Funded by: Octapharma AG
                Award ID: N/A
                Funded by: LFB Biomédicaments
                Award ID: N/A
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                coagulopathy,emergency medicine,haemostasis,practice guideline,trauma
                Emergency medicine & Trauma
                coagulopathy, emergency medicine, haemostasis, practice guideline, trauma

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