Management of Bleeding and Coagulopathy Following Major Trauma

Spahn et al. Critical Care 2013, 17:R76 http://ccforum.com/content/17/2/R76 RESEARCH Open Access Management of bleeding and coagulopathy following major trauma: an updated European guideline Donat R Spahn1, Bertil Bouillon2, Vladimir Cerny3,4, Timothy J Coats5, Jacques Duranteau6, Enrique Fernández-Mondéjar7, Daniela Filipescu8, Beverley J Hunt9, Radko Komadina10, Giuseppe Nardi11, Edmund Neugebauer12, Yves Ozier13, Louis Riddez14, Arthur Schultz15, Jean-Louis Vincent16 and Rolf Rossaint17* Abstract Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond. Introduction among these patients [2,3]. Appropriate management of Severe trauma is one of the major health care issues the massively bleeding trauma patient includes the early faced by modern society, resulting in the annual death identification of bleeding sources followed by prompt of more than five million people worldwide, and this measures to minimise blood loss, restore tissue perfu- number is expected to increase to more than eight mil- sion and achieve haemodynamic stability. lion by 2020 [1]. Uncontrolled post-traumatic bleeding An awareness of the specific pathophysiology asso- is the leading cause of potentially preventable death ciated with bleeding following traumatic injury by treat- ing physicians is essential. About one-third of all bleeding trauma patients present with a coagulopathy * Correspondence: [email protected] 17Department of Anaesthesiology, University Hospital Aachen, RWTH Aachen upon hospital admission [4-7]. This subset of patients University, Pauwelsstrasse 30, D-52074 Aachen, Germany has a significantly increased incidence of multiple organ Full list of author information is available at the end of the article © 2013 Spahn 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. Spahn et al. Critical Care 2013, 17:R76 Page 2 of 45 http://ccforum.com/content/17/2/R76 failure and death compared to patients with similar combination of bleeding-induced shock, tissue injury- injury patterns in the absence of a coagulopathy related thrombin-thrombomodulin-complex generation [4,5,7,8]. The early acute coagulopathy associated with and the activation of anticoagulant and fibrinolytic path- traumatic injury has recently been recognised as a mul- ways (Figure 1) [5-7,9-11]. Moreover, it has been shown tifactorial primary condition that results from a that high circulating levels of syndecan-1, a marker of Pre-existing factors • Genetics • Medical illness • Medication (especially antithrombotics) TRAUMA Activation of INFLAMMATION Loss of haemostatic factors due to HAEMORRHAGE FIBRINOLYSIS Shock Activation of Tissue haemostasis Resuscitation hypoxia & endothelium Crystalloid RBC Acidosis & colloid transfusion Dilutional coagulopathy TRAUMATIC COAGULOPATHY Figure 1 Current concepts of pathogenesis of coagulopathy following traumatic injury. Adapted from [9,10]. Spahn et al. Critical Care 2013, 17:R76 Page 3 of 45 http://ccforum.com/content/17/2/R76 endothelial glycocalyx degradation, is associated with guiding principles to the local situation and implemen- coagulopathy in trauma patients [12]. Different factors tation within each institution. We believe that adherence influence the severity of the coagulation disorder. On to the local management protocol should be assessed, one hand, coagulopathy is influenced by environmental and that such regular compliance assessments should be and therapeutic factors that result in or at least contri- part of institutional quality management processes, and bute to acidaemia, hypothermia, dilution, hypoperfusion that personnel training to ensure compliance should be and coagulation factor consumption [5,6,9,13-15]. On adapted accordingly. If followed, these clinical practice the other hand, this condition is modified by individual guidelines have the potential to ensure a uniform stan- patient-related factors, including genetic background, dard of care across Europe and beyond. co-morbidities, inflammation and medications, especially oral anticoagulants, and pre-hospital fluid administration Materials and methods [15-17]. A recent paper suggests that the severity of These recommendations were formulated and graded traumatic brain injury (TBI) represents a further indivi- according to the Grading of Recommendations Assess- dual patient-related factor that may contribute to acute ment, Development and Evaluation (GRADE) hierarchy traumatic coagulopathy [18]. A number of terms have of evidence [24-26] summarised in Table 1. Comprehen- been proposed to describe the condition, which is dis- sive computer database literature searches were per- tinct from disseminated intravascular coagulation, formed using the indexed online database MEDLINE/ including Acute Traumatic Coagulopathy [6,19], Early PubMed. Lists of cited literature within relevant articles Coagulopathy of Trauma [7], Acute Coagulopathy of were also screened. The primary intention of the review Trauma-Shock [9], Trauma-Induced Coagulopathy [20] was to identify prospective randomised controlled trials and Trauma-Associated Coagulopathy [21]. (RCTs) and non-RCTs, existing systematic reviews and This European guideline, originally published in 2007 guidelines. In the absence of such evidence, case-control [22] and updated in 2010 [23], represents a second studies, observational studies and case reports were update and is part of the European “STOP the Bleeding considered. Campaign“, an international initiative launched in 2013 Boolean operators and Medical Subject Heading to reduce morbidity and mortality associated with bleed- (MeSH) thesaurus keywords were applied as a standar- ing following traumatic injury. The campaign aims to dised use of language to unify differences in terminology support haemostatic resuscitation measures by providing into single concepts. Appropriate MeSH headings and clinical practice guidelines to ensure the early recogni- subheadings for each question were selected and modi- tion and treatment of bleeding and traumatic coagulopa- fied based on search results. The scientific questions thy. The acronym STOP stands for Search for patients posed that led to each recommendation and the MeSH at risk of coagulopathic bleeding, Treat bleeding and headings applied to each search are listed in Additional coagulopathy as soon as they develop, Observe the file 1. Searches were limited to English-language abstracts response to interventions and Prevent secondary bleed- and human studies; gender and age were not limited. The ing and coagulopathy. As part of the campaign, this time period was limited to the past three years for ques- guideline should not only provide a better understand- tions addressed in the 2010 version of the guideline. A ing of the pathophysiologyoftheseverelybleeding time period limit of 10 years was applied to new searches patient following traumatic injury and treatment gui- yielding more than 500 hits; otherwise no time-period lim- dance for the clinician, but also highlight the areas in its were imposed. Abstracts from original publications which further research is urgently required. The recom- were screened for relevance and full publications evaluated mendations for in-hospital patient management have where appropriate. Some additional citations that were been adapted to reflect the evidence published during published after the literature search cut-off for the guide- the last three years,

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