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.

Dried Plasma

“…Neuroprotective effects of plasma in hemorrhagic shock and TBI are thought to be due to improved cerebral perfusion, decreased glutamate-mediated excitotoxicity, and reduction in mitochondrial dysfunction as demonstrated in animal models [28]. Plasma also reduced the size of brain lesions and swelling in multiple swine models of TBI and hemorrhagic shock [29,30]. It also incurs neuroprotection by providing higher brain oxygenation and cerebral perfusion profiles [30].…”

“…Plasma also reduced the size of brain lesions and swelling in multiple swine models of TBI and hemorrhagic shock [29,30]. It also incurs neuroprotection by providing higher brain oxygenation and cerebral perfusion profiles [30]. In humans, a large retrospective cohort analysis showed that in the subgroup of patients with multifocal intracranial hemorrhage, early administration of plasma was associated with a survival benefit [31].…”

Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury

“…Compared with other resuscitation fluids such as fresh frozen plasma (FFP) or colloids, normal saline resuscitation is furthermore associated with increased brain swelling (Jin, DeMoya, et al (2012;Imam et. al.…”

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

“…Our group and others have demonstrated that the choice of resuscitation fluid plays an important role in the severity of secondary brain injury. 21,53,54 Compared with crystalloids, artificial colloids (e.g. HEX), and fresh frozen plasma (FFP) have shown an increased ability to limit the extent of brain lesion size and swelling.…”

“…HEX), and fresh frozen plasma (FFP) have shown an increased ability to limit the extent of brain lesion size and swelling. 21,53 While fluids do influence gene expression, such effects are likely minor compared with epigenetic modulators such as VPA, a known HDACI.…”