title: Fresh frozen plasma resuscitation provides neuroprotection compared to normal saline in a large animal model of traumatic brain injury and polytrauma.
abstract: We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2 h of shock (mean arterial pressure, 30-35 mm Hg), animals were resuscitated with normal saline (NS; 3×volume) or FFP (1×volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9 mm(3); p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4 ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.
authors.affiliation: 1 Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School , Boston, Massachusetts.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Imam
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Simone E
authors.initials: SE
authors.lastname: Dekker
authors.forename: Ted
authors.initials: T
authors.lastname: Bambakidis
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: Ihab
authors.initials: I
authors.lastname: Halaweish
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D009104:Multiple Trauma / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010949:Plasma; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy; D034421:Sus scrofa
chemical_list: D018696:Neuroprotective Agents
keywords: brain; hemorrhage; plasma; resuscitation; trauma