title: Use of recombinant factor VIIa (rFVIIa) as pre-hospital treatment in a swine model of fluid percussion traumatic brain injury.
abstract: BACKGROUND
  Recombinant factor VIIa (rFVIIa) has been used as an adjunctive therapy for acute post-traumatic hemorrhage and reversal of iatrogenic coagulopathy in trauma patients in the hospital setting. However, investigations regarding its potential use in pre-hospital management of traumatic brain injury (TBI) have not been conducted extensively.
  
  
  OBJECTIVE
  In the present study, we investigated the physiology, hematology and histology effects of a single pre-hospital bolus injection of rFVIIa compared to current clinical practice of no pre-hospital intervention in a swine model of moderate fluid percussion TBI.
  
  
  METHODS
  Animals were randomized to receive either a bolus of rFVIIa (90 μg/kg) or nothing 15 minutes (T15) post-injury. Hospital arrival was simulated at T60, and animals were euthanized at experimental endpoint (T360).
  
  
  RESULTS
  Survival was 100% in both groups; baseline physiology parameters were similar, vital signs were comparable. Animals that received rFVIIa demonstrated less hemorrhage in subarachnoid space (P = 0.0037) and less neuronal degeneration in left hippocampus, pons, and cerebellum (P = 0.00009, P = 0.00008, and P = 0.251, respectively). Immunohistochemical staining of brain sections showed less overall loss of microtubule-associated protein 2 (MAP2) and less Flouro-Jade B positive cells in rFVIIa-treated animals.
  
  
  CONCLUSIONS
  Early pre-hospital administration of rFVIIa in this swine TBI model reduced neuronal necrosis and intracranial hemorrhage (ICH). These results merit further investigation of this approach in pre-hospital trauma care.
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Bobby
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA ; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Françoise G
authors.initials: FG
authors.lastname: Arnaud
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Teranishi
authors.affiliation: Department of Veterinary Pathology, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steinbach
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Auker
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA ; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: McCarron
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA ; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
authors.affiliation: Department of Neuro Trauma, Naval Medical Research Center, Silver Spring, Maryland, USA ; Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Scultetus
keywords: Coagulopathy; necrosis; pre-hospital; rFVIIa; swine; traumatic brain injury