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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 references23

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          Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.

          Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso. We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room. Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group. For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.
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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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              The microcirculation is the motor of sepsis

              Can Ince (2005)
              Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition microcirculatory and mitochondrial distress syndrome (MMDS). Orthogonal polarization spectral imaging allowed the first clinical observation of the microcirculation in human internal organs, and has identified the pivotal role of microcirculatory abnormalities in defining the severity of sepsis, a condition not revealed by systemic hemodynamic or oxygen-derived variables. Recently, sublingual sidestream dark-field (SDF) imaging has been introduced, allowing observation of the microcirculation in even greater detail. Microcirculatory recruitment is needed to ensure adequate microcirculatory perfusion and the oxygenation of tissue cells that follows. In sepsis, where inflammation-induced autoregulatory dysfunction persists and oxygen need is not matched by supply, the microcirculation can be recruited by reducing pathological shunting, promoting microcirculatory perfusion, supporting pump function, and controlling hemorheology and coagulation. Resuscitation following MMDS must include focused recruitment of hypoxic-shunted microcirculatory units and/or resuscitation of the mitochondria. A combination of agents is required for successful rescue of the microcirculation. Single compounds such as activated protein C, which acts on multiple pathways, can be expected to be beneficial in rescuing the microcirculation in sepsis.
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                Author and article information

                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
                : 17
                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
                Article
                88
                10.1186/s40635-016-0088-z
                4920780
                27342821
                53836e3e-0895-49ed-af9a-9ef673f390b5
                © 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

                History
                : 9 February 2016
                : 30 May 2016
                Funding
                Funded by: Ministry of Defence (UK)
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                haemorrhagic shock,microcirculation,traumatic injury,sublingual video-microscopy,lactate clearance,co2 gap,blood products,perfused vessel density

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