Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma

Abstract

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Dried Plasma

“…The brain lesion size was significantly smaller in LP group on experiment day 3, but this effect dissipated by day 10 [75]. Another large 30-day animal study recently showed similar neuroprotective results with faster return to baseline neurological function in animals treated with LP and FFP vs. NS [76].…”

Response to: “Misunderstanding the PROPPR trial”

“…New large-animal data from the Alams group and observational data from our center suggest that plasma may improve outcomes after severe TBI. 6,7 The proposed mechanism is less related to coagulopathy and more focused on repairing the blood-brain barrier, minimizing secondary injury. 8 This area needs to be explored.…”

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury

“…In 2005, Chhabra and co‐workers showed that the N‐terminal fragment of gelsolin could bind to and disrupt actin–DNase complexes, in turn restoring enzymatic activity. FFP is not only effective in treating trauma but was shown previously to attenuate extracellular nucleosome levels and depletion of DNase, and to provide neuroprotection in models of traumatic brain injury.…”