Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults

Shock. 2012 Jul;38(1):49-56. doi: 10.1097/SHK.0b013e3182574778.


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.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Edema / etiology
  • Brain Edema / pathology
  • Brain Edema / therapy
  • Brain Injuries / complications*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Brain Injuries / therapy
  • Carbon Dioxide / blood
  • Disease Models, Animal
  • Female
  • Hemodynamics / physiology
  • Hydroxyethyl Starch Derivatives / therapeutic use
  • Intracranial Pressure / physiology
  • Oxygen / blood
  • Partial Pressure
  • Plasma
  • Resuscitation / methods*
  • Shock, Hemorrhagic / etiology*
  • Shock, Hemorrhagic / physiopathology
  • Shock, Hemorrhagic / therapy
  • Sodium Chloride / therapeutic use
  • Sus scrofa


  • Hydroxyethyl Starch Derivatives
  • Carbon Dioxide
  • Sodium Chloride
  • Oxygen