title: Traumatic brain injury and hemorrhagic shock:  evaluation of different resuscitation strategies in a large animal model of combined insults.
abstract: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.
authors.affiliation: Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Marc A
authors.initials: MA
authors.lastname: DeMoya
authors.forename: Michael
authors.initials: M
authors.lastname: Duggan
authors.forename: Thomas
authors.initials: T
authors.lastname: Knightly
authors.forename: Ali Y
authors.initials: AY
authors.lastname: Mejaddam
authors.forename: John
authors.initials: J
authors.lastname: Hwabejire
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lu
authors.forename: William Michael
authors.initials: WM
authors.lastname: Smith
authors.forename: Georgios
authors.initials: G
authors.lastname: Kasotakis
authors.forename: George C
authors.initials: GC
authors.lastname: Velmahos
authors.forename: Simona
authors.initials: S
authors.lastname: Socrate
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000628:therapy; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D007427:Intracranial Pressure / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010949:Plasma; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D012965:Sodium Chloride / Q000627:therapeutic use; D034421:Sus scrofa
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D002245:Carbon Dioxide; D012965:Sodium Chloride; D010100:Oxygen