title: 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.
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 CO2 gradient. There was no significant difference in blood pressure between the two groups at any stage.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Birmingham, B15 2SQ, UK. sam.hutchings@kcl.ac.uk.|Department of Critical Care, King's College Hospital London, Denmark Hill, London, SE5 9RS, UK. sam.hutchings@kcl.ac.uk.|Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK. sam.hutchings@kcl.ac.uk.
authors.forename: Sam D
authors.initials: SD
authors.lastname: Hutchings
authors.affiliation: Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Birmingham, B15 2SQ, UK.|NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, B152TH, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Naumann
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Watts
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
authors.forename: Callie
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Burton
authors.affiliation: Department of Critical Care, King's College Hospital London, Denmark Hill, London, SE5 9RS, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
authors.forename: Emrys
authors.initials: E
authors.lastname: Kirkman
keywords: Blood products; CO2 gap; Haemorrhagic shock; Lactate clearance; Microcirculation; Perfused vessel density; Sublingual video-microscopy; Traumatic injury