title: Early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock.
abstract: Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In previous models of combined TBI + HS, we showed that early resuscitation with fresh frozen plasma (FFP) improves neurologic outcomes. Delivering FFP, however, in austere environments is difficult. Lyophilized plasma (LP) is a logistically superior alternative to FFP, but data are limited regarding its efficacy for treatment of TBI. We conducted this study to determine the safety and long-term outcomes of early treatment with LP in a large animal model of TBI + HS.
  
  
  
  Adult anesthetized swine underwent TBI and volume-controlled hemorrhage (40% blood volume) concurrently. After 2 hours of shock, animals were randomized (n = 5 per /group) to FFP or LP (1× shed blood) treatment. Serial blood gases were drawn, and thromboelastography was performed on citrated, kaolin-activated whole-blood samples. Five hours after treatment, packed red blood cells were administered, and animals recovered. A 32-point Neurologic Severity Score was assessed daily for 30 days (0 = normal, 32 = most severe injury). Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Brain lesion size was measured on serial magnetic resonance imaging, and an autopsy was performed at 30 days.
  
  
  
  The severity of shock and the degree of resuscitation were similar in both groups. Administration of FFP and LP was well tolerated with no differences in reversal of shock or thromboelastography parameters. Animals in both groups displayed the worst Neurologic Severity Score on postoperative Day 1 with rapid recovery and return to baseline within 7 days of injury. Lesion size on Day 3 in FFP-treated animals was 645 ± 85 versus 219 ± 20 mm in LP-treated animals (p < 0.05). There were no differences in cognitive functions or delayed treatment-related complications.
  
  
  
  Early treatment with LP in TBI + HS is safe and provides neuroprotection that is comparable to FFP.
authors.affiliation: From the Department of Surgery, University of Michigan, Ann Arbor, Michigan (I.H., T.B., V.N., P.G., P.P., B.L., Y.L., H.B.A.); Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen Hospital, Copenhagen, Denmark (P.B.); Center for Regenerative Medicine, Oregon Health & Science University, Portland, Oregon (L.B.); and Department of Radiology, Section of Neuroradiology, University of Michigan, Ann Arbor, Michigan (A.S.).
authors.forename: Ihab
authors.initials: I
authors.lastname: Halaweish
authors.forename: Ted
authors.initials: T
authors.lastname: Bambakidis
authors.forename: Vahagn C
authors.initials: VC
authors.lastname: Nikolian
authors.forename: Patrick
authors.initials: P
authors.lastname: Georgoff
authors.forename: Peter
authors.initials: P
authors.lastname: Bruhn
authors.forename: Patryk
authors.initials: P
authors.lastname: Piascik
authors.forename: Lisa
authors.initials: L
authors.lastname: Buckley
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Baoling
authors.initials: B
authors.lastname: Liu
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005612:Freeze Drying; D010949:Plasma; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013552:Swine