• Umar F Bhatti, Zaiba Shafik Dawood, Zhenhua Shang, Guang Jin, Marjorie R Liggett, Kiril Chtraklin, Baoling Liu, Ramon-Lorenzo Redondo, Bowen Wang, and Hasan B Alam.
• Department of Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL.
• J. Am. Coll. Surg. 2024 Oct 21.

BackgroundProlonged Field Care (PFC) is a military adaptation of Tactical Combat Casualty Care providing extended pre-hospital management during delayed extrication. Effects of addition of Valproic Acid (VPA) to Fresh Frozen Plasma (FFP) in a PFC model of hemorrhagic shock and traumatic brain injury (TBI) are not known. We hypothesized that VPA is associated with decreased neurological impairment, and its protective changes are detected at the transcriptomic level.Study DesignSwine underwent TBI and 40%-blood volume hemorrhage. After 2-hours of shock, they were randomized to: 1)normal saline (NS), 2)NS+250 ml FFP (NS+FFP), or 3)NS+FFP+150 mg/kgVPA(NS+FFP+VPA). At 72-hours, they were transfused packed red blood cells before being euthanized. Intraoperative variables and neurological outcomes were compared. Brain lesion size was measured, and gene expression profiles were analyzed using RNA-sequencing. Pathway and network analyses were performed on differentially expressed genes. Real-time PCR was performed to validate key genes.ResultsNS+FFP and NS+FFP+VPA required significantly less crystalloid resuscitation(974 ml-NS+FFP; 1461ml-NS+FFP+VPA vs. 4540 ml-NS, p<0.001), had smaller brain lesion size(2477mm3-NS+FFP; 3018.0mm3-NS+FFP+VPA vs. 4517.0mm3-NS, p<0.01), and less functional neurologic impairment compared to NS. Per pathway analysis of differentially expressed genes, VPA was associated with enrichment of numerous metabolic changes in injured brains, which were not observed with FFP. Network analysis showed enrichment of various gene networks. MT-ATP8 gene was downregulated in VPA-treated animals.ConclusionsThe addition of FFP to the resuscitation protocol resulted in a significant reduction in crystalloid requirements. Both, the FFP and FFP+VPA groups showed improved neurological recovery compared to NS alone and had distinctive transcriptomic profiles in injured brains at 72-hours. MT-ATP8, involved in worsening ischemia following brain injury, was down-regulated in VPA-treated animals.Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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