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Microcirculatory perfusion shows wide inter-individual variation and is important in determining shock reversal during resuscitation in a porcine experimental model of complex traumatic hemorrhagic shock

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      Abstract

      Background

      Traumatic hemorrhagic shock (THS) is a leading cause of preventable death following severe traumatic injury. Resuscitation of THS is typically targeted at blood pressure, but the effects of such a strategy on systemic and microcirculatory flow remains unclear. Failure to restore microcirculatory perfusion has been shown to lead to poor outcomes in experimental and clinical studies. Systemic and microcirculatory variables were examined in a porcine model of complex THS, in order to investigate inter-individual variations in flow and the effect of microcirculatory perfusion on reversal of the shock state.

      Methods

      Baseline standard microcirculatory variables were obtained for 22 large white pigs using sublingual incident dark field (IDF) video-microscopy. All animals were subjected to a standardised hind-limb injury followed by a controlled haemorrhage of approximately 35 % of blood volume (shock phase). This was followed by 60 min of fluid resuscitation with either 0.9 % saline or component blood products and a target SBP of 80 mmHg (early resuscitation phase). All animals were then given blood products to a target SBP of 110 mmHg for 120 min (mid-resuscitation phase), and a further 100 min (late resuscitation phase). IDF readings were obtained at the midpoint of each of these phases. Cardiac output was measured using a pulmonary artery catheter. Animals were divided into above average (A) and below average (B) perfused vessel density (PVD) groups based on the lowest recorded PVD measurement taken during the shock and early resuscitation phases.

      Results

      There was minimal inter-individual variation in blood pressure but wide variation of both systemic and microcirculatory flow variables during resuscitation. During shock and early resuscitation, group A ( n = 10) had a mean PVD of 10.5 (SD ± 2.5) mm/mm 2 and group B ( n = 12) 5.5 (SD ± 4.1) mm/mm 2. During the later resuscitation phases, group A maintained a significantly higher PVD than group B. Group A initially had a higher cardiac output, but the difference between the groups narrowed as resuscitation progressed. At the end of resuscitation, group A had significantly lower plasma lactate, higher lactate clearance, lower standard base deficit and smaller mixed venous-arterial CO 2 gradient. There was no significant difference in blood pressure between the two groups at any stage.

      Conclusion

      There was a wide variation in both macro- and microcirculatory flow variables in this pressure-targeted experimental model of THS resuscitation. Early changes in microvascular perfusion appear to be key determinants in the reversal of the shock state during resuscitation. Microcirculatory flow parameters may be more reliable markers of physiological insult than pressure-based parameters and are potential targets for goal-directed resuscitation.

      Electronic supplementary material

      The online version of this article (doi:10.1186/s40635-016-0088-z) contains supplementary material, which is available to authorized users.

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      Most cited references 27

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      How to evaluate the microcirculation: report of a round table conference

      Introduction Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis. Methods The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology. Results The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future. Conclusion We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index.
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        Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations.

        The world-wide impact of traumatic injury and associated hemorrhage on human health and well-being cannot be overstated. Twelve percent of the global disease burden is the result of violence or accidental injury. Hemorrhage is responsible for 30 to 40% of trauma mortality, and of these deaths, 33 to 56% occur during the prehospital period. Among those who reach care, early mortality is caused by continued hemorrhage, coagulopathy, and incomplete resuscitation. The techniques of early care, including blood transfusion, may underlie late mortality and long-term morbidity. While the volume of blood lost cannot be measured, physiologic and chemical measures and the number of units of blood given are readily recorded and analyzed. Improvements in early hemorrhage control and resuscitation and the prevention and aggressive treatment of coagulopathy appear to have the greatest potential to improve outcomes in severely injured trauma patients.
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          Management of bleeding and coagulopathy following major trauma: an updated European guideline

          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. Please see related letter by Morel et al http://ccforum.com/content/17/4/442
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            Author and article information

            Affiliations
            [ ]Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Birmingham, B15 2SQ UK
            [ ]Department of Critical Care, King’s College Hospital London, Denmark Hill, London, SE5 9RS UK
            [ ]Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ UK
            [ ]NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, B152TH UK
            Contributors
            sam.hutchings@kcl.ac.uk
            Journal
            Intensive Care Med Exp
            Intensive Care Med Exp
            Intensive Care Medicine Experimental
            Springer International Publishing (Cham )
            2197-425X
            24 June 2016
            24 June 2016
            December 2016
            : 4
            27342821 4920780 88 10.1186/s40635-016-0088-z
            © Content includes material subject to Crown copyright, Dstl. 2016

            This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gsi.gov.uk

            Funding
            Funded by: Ministry of Defence (UK)
            Categories
            Research
            Custom metadata
            © The Author(s) 2016

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