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

Guang Jin, Marc A. Demoya, Michael Duggan, Thomas Knightly, Ali Y. Mejaddam, John Hwabejire, Jennifer Lu, William Michael Smith, Georgios Kasotakis, George C. Velmahos, Simona Socrate, Hasan B. Alam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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 ± 202.6 mm 3 and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm 3 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.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
Issue number1
StatePublished - Jul 2012
Externally publishedYes


  • edema
  • hemorrhage
  • shock
  • swine
  • Traumatic brain injury

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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