Shock, Whole Blood, and Assessment of TBI S.W.A.T. (LITES TO 2)
Condition: Hemorrhagic Shock; Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Shock; Shock, Hemorrhagic
Study type: Observational

Summary: 
      The LITES Network is an operational trauma center consortium which has the expertise, track
      record and confirmed capabilities to conduct prospective, multicenter, injury care and
      outcomes research of relevance to the Department of Defense (DoD).

      Hemorrhage and Traumatic Brain Injury (TBI) are responsible for the largest proportion of all
      trauma-related deaths. It is the poly-trauma patient who suffers both hemorrhagic shock and
      traumatic brain injury where a paucity of evidence exists to direct treatment, limiting the
      development of beneficial trauma practice guidelines.

      The use of Whole Blood (WB) for early trauma resuscitation has been touted as the 'essential
      next step' in the evolution of trauma resuscitation. Despite its historical and more recent
      use, little is known regarding WB's benefit relative to the 'current practice' ratio-based
      blood component therapy in the acutely bleeding patient, and even less is known regarding its
      effects in patients with TBI.

      AIM#1: Evaluate patient centered outcomes associated with early whole blood resuscitation
      practice as compared to component resuscitation in poly-trauma patients with hemorrhagic
      shock and further characterize outcome benefits in those with traumatic brain injury.

      AIM#2: Characterize blood pressure and resuscitation endpoints during the acute resuscitation
      phase of care and the associated/attributable outcomes for traumatic brain injury in patients
      with hemorrhagic shock.

      General Hypothesis #1: Whole blood resuscitation will be associated with improved mortality
      and resuscitation outcomes in poly-trauma patients and long term neurological outcome in
      those patients with traumatic brain injury as compared to those resuscitated with component
      therapy.

      General Hypothesis #2: Differences in prehospital and acute phase resuscitation systolic
      blood pressure will be associated with differential outcomes in patients with traumatic brain
      injury at discharge and at 6 months.

      Study Design: The LITES network will perform a multicenter, prospective, observational cohort
      study over a 4 year period to determine the impact of whole blood resuscitation in trauma
      patients with hemorrhagic shock at risk of large volume resuscitation with and without TBI.
      Early whole blood resuscitation will be compared to standard component resuscitation. The
      study will also further characterize blood pressure and resuscitation endpoints in
      poly-trauma patients with traumatic brain injury. Six Trauma sites with appropriate
      characteristics will be selected from 12 LITES Network sites across the country.

      Study Setting: The study will be performed utilizing busy level I trauma centers within the
      LITES Network located across the country, at sites where either whole blood has currently
      been incorporated into standard of care or where component blood transfusion is being
      utilized for patients in hemorrhagic shock at risk for large volume resuscitation.

      Study Population: The study will focus on patients who suffer blunt or penetrating injury,
      transported to a SWAT participating LITES trauma center with evidence of hemorrhagic shock at
      risk of large volume blood resuscitation.
    

Detailed description: 
      Background

      The LITES Network is an operational trauma center consortium which has the expertise, track
      record and confirmed capabilities to conduct prospective, multicenter, injury care and
      outcomes research of relevance to the Department of Defense (DoD). Clinical trials from the
      point of injury in the prehospital arena through the trauma bay and operating theatre, thru
      ICU and beyond discharge are feasible and critical to the overall goals of the network. Novel
      capabilities include prehospital point of care testing for shock severity and sequential
      coagulopathy measurements. The network and leadership have a track record of Exception From
      Informed Consent (EFIC) trials and expertise with those injury subtypes including traumatic
      brain injury, hemorrhagic shock and coagulopathy of trauma, poly-trauma and severe extremity
      trauma. In addition to the track record and proven capabilities, the LITES Network uses a
      central IRB and efficient methods to minimize time, resources, cost and regulatory burdens
      and improve recruitment, consent rates and ease of data acquisition to promote successful
      execution of those task orders provided to the network from the DoD.

      Traumatic injury represents an incredible health care burden in the United States and
      worldwide.1 Hemorrhage and Traumatic Brain Injury (TBI) are responsible for the largest
      proportion of all trauma-related deaths. Despite advances in trauma resuscitation and brain
      injury management, few therapeutic interventions are available to reduce the downstream
      morbidity and mortality attributable to these injury patterns. It is the poly-trauma patient
      who suffers both hemorrhagic shock and traumatic brain injury where a paucity of evidence
      exists to direct treatment, limiting the development of beneficial trauma practice
      guidelines.

      Ongoing traumatic blood loss is complicated by trauma induced coagulopathy which results in
      further unbridled hemorrhage and resultant shock and organ dysfunction. Secondary to
      increasing evidence and knowledge, in-hospital resuscitation of traumatic hemorrhage has
      changed over the past decade to reduce the coagulopathic response to ischemia and tissue
      injury. The underlying principle of current resuscitation practice focuses on preventing or
      reversing the effects of coagulopathy with the early use of a balanced component transfusion
      strategy (1:1:1 - plasma: packed red blood cells: platelets). This reconstituted strategy has
      also been coined 'whole blood-like' resuscitation despite being inferior from a compositional
      standpoint relative to Whole Blood (WB). The use of WB was historically the gold standard for
      treating hemorrhagic shock during World War I and II, prior to sweeping changes in blood
      banking practice. The use of WB for early trauma resuscitation is making a resurgence,
      primarily based upon the military experience and has been touted as the 'essential next step'
      in the evolution of trauma resuscitation. Despite its historical and more recent use, little
      is known regarding WB's benefit relative to the 'current practice' ratio based blood
      component therapy in the acutely injured patients and even less is known regarding its
      effects in patients with TBI.

      Permissive hypotension has been thought to improve outcome in injured patients with
      hemorrhagic shock in the prehospital and acute resuscitation phase of treatment allowing for
      the ability to obtain surgical control of bleeding while minimizing ongoing hemorrhage.
      Despite this benefit for hemorrhagic shock patients, hypotension has been consistently shown
      to be associated with worse outcomes in patients with TBI. Interestingly, newer animal data
      suggests permissive hypotension may be beneficial in a swine TBI model.The majority of prior,
      high level TBI trials have excluded patients with concomitant hemorrhagic shock. Prospective
      evidence and long term TBI outcome data are lacking for these complex poly-trauma patients
      and the most appropriate blood pressure and most efficacious resuscitation target for
      patients with TBI and acute hemorrhage remain poorly characterized.

      Hypothesis #1A: Whole blood resuscitation will be associated with a lower 4 hour mortality in
      poly-trauma patients as compared to those resuscitated with component therapy.

      Hypothesis #1B: Whole blood resuscitation will be associated with a lower incidence of 12
      hour and 24 hour mortality, a lower incidence of death from exsanguination, incidence of MOF,
      nosocomial infection, improved transfusion ratios, lower overall blood transfusion
      requirements and shorter time to hemostasis as compared to those resuscitated with component
      therapy.

      Hypothesis #1C: Whole blood resuscitation will be associated with an improved Glasgow Outcome
      Score-Extended at 6 months post injury as compared to those resuscitated with component
      therapy in patients with traumatic brain injury.

      Hypothesis #2A: A nadir prehospital and acute phase resuscitation systolic blood pressure
      greater than or equal to 120 mmHg will be associated with improved traumatic brain injury
      outcomes at discharge and at 6 months.

      Hypothesis #2B: The magnitude of the dose depth curve of systolic blood pressure during the
      prehospital and acute phase resuscitation will be associated with neurological outcome
      differences at discharge and at 6 months following traumatic brain injury.

      Research Design and Methods

      Study Design: The LITES Network will perform a multicenter, prospective, observational cohort
      study over a 4 year period to determine the impact of whole blood resuscitation in trauma
      patients with hemorrhagic shock at risk of large volume resuscitation with and without TBI.
      Early whole blood resuscitation will be compared to standard component resuscitation. The
      study will also further characterize blood pressure and resuscitation endpoints in
      poly-trauma patients with traumatic brain injury. Six trauma sites with appropriate
      characteristics will be selected from 12 network sites across the country.

      Study Setting: The study will be performed utilizing busy level I trauma centers from within
      the LITES Network located across the country, at sites where either whole blood has currently
      been incorporated into standard of care or where component blood transfusion is being
      utilized for patients in hemorrhagic shock at risk for large volume resuscitation. Due to the
      paucity of trauma centers who are currently utilizing whole blood for trauma patients as
      standard of care, the potential to incorporate sites outside of the current LITES Network may
      be required over time.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study will focus on patients who suffer blunt or penetrating injury, transported to a
        SWAT participating LITES trauma center with evidence of hemorrhagic shock at risk of large
        volume resuscitation.
      
Biospecimen description: 
      Mechanistic Banked Samples Mechanistic Biomarkers
    
Keywords: Whole Blood Resuscitation