title: Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock.
abstract: BACKGROUND
  Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP.
  
  
  METHODS
  Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced (40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured.
  
  
  RESULTS
  This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly (p < 0.05) decreased brain lesion size and swelling (51% and 54%, respectively).
  
  
  CONCLUSIONS
  In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care, (A.M.I., G.J., M.S., M.D., C.H.J., J.O.H., J.L., M.A.D., G.C.V., H.B.A.), Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; and Department of Surgery (G.J., B.L., H.B.A.), University of Michigan Hospital, Ann Arbor, Michigan.
authors.forename: Ayesha M
authors.initials: AM
authors.lastname: Imam
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Michael
authors.initials: M
authors.lastname: Duggan
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lu
authors.forename: Baoling
authors.initials: B
authors.lastname: Liu
authors.forename: Marc A
authors.initials: MA
authors.lastname: DeMoya
authors.forename: George C
authors.initials: GC
authors.lastname: Velmahos
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D007427:Intracranial Pressure; D010949:Plasma; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D016896:Treatment Outcome