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Traumatic Brain Injury and Hemorrhagic Shock: Evaluation of Different Resuscitation Strategies in a Large Animal Model of Combined Insults
*Guang Jin1, *Michael Duggan1, *Georgios Kasotakis1, *Thomas Knightly1, *Ali Majaddam1, *Wei Chong1, *Jennifer Lu1, *Marc A deMoya1, *David R King1, George C Velmahos1, *Simona Socrate2, *Hasan B. Alam1
1Massachusetts General Hospital/Harvard, Boston, MA;2Massachusetts Institute of Technology, Boston, MA

Objective: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) (TBI+HS) is highly lethal, and the optimal resuscitation strategy for this insult remains unclear. We used a clinically relevant large animal model of TBI+HS to evaluate the impact of different treatments on brain lesion size and associated edema.
Design: Controlled in-vivo study
Setting: University hospital research laboratory
Subjects: Yorkshire swine (42-50 kg)
Interventions: A computer- controlled cortical impact device was used to create TBI: 15 mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time and 12 mm penetration depth. After 2 hours of 40 % volume-controlled hemorrhage shock, animals were randomized to one of three resuscitation groups (n=4-5/gr): 1) normal saline (NS), 2) 6% hetastarch, Hextend (Hex), 3) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was 3X the volume.
Main Outcome Measures: Brain lesion size and edema.
Results: Combination of 40% blood loss with cortical impact and a period of shock (2 hours) resulted in a highly reproducible TBI. Changes in blood pressure, intra-cranial pressure, and brain oxygen tension were clinically realistic. Six hours post-resuscitation, lesion size and brain swelling in the FFP group (2304.2 ± 368.0 mm3, and 22 ± 2.5% respectively) were significantly less than the NS group (3450.2 ± 262.3 mm3, and 37 ± 1.9% respectively). Hex treatment decreased the swelling (25 ± 3.1%) but did not influence the lesion size.
Conclusion: Early administration of FFP reduces the size of brain lesion and edema in a large animal model of TBI+HS. In contrast, artificial colloid (Hex) decreases the swelling without reducing the actual size of the brain lesion.


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