Valproic acid decreases resuscitation requirements after hemorrhage in a prolonged damage-control resuscitation model

Ben E. Biesterveld, Aaron M. Williams, Michael T. Kemp, Glenn K. Wakam, Ali Z. Siddiqui, Rachel L. O'Connell, Alizeh Shamshad, Kiril Chtraklin, Umar F. Bhatti, Yongqing Li, Hasan B. Alam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND Hemorrhage is the leading cause of preventable death in trauma. Future military conflicts are likely to be in austere environments, where prolonged damage-control resuscitation (p-DCR) may be required for 72 hours before evacuation. There is a need to demonstrate that p-DCR is feasible and to optimize its logistics. Dried plasma (DP) is a practical alternative to conventional blood products in austere settings, and valproic acid (VPA) improves survival in preclinical models of trauma and hemorrhage. We performed the current experiment to study the synergistic effects of VPA and DP and hypothesized that VPA treatment would decrease the fluid resuscitation requirements in p-DCR. METHODS Female swine were subjected to 50% hemorrhage (associated with 20% survival using non-plasma-based p-DCR) and left unresuscitated for 1 hour to simulate medic response time. They were then randomized to receive VPA (150 mg/kg + DP 250 mL; DP-VPA group; n = 5) or DP alone (DP group; n = 6). All animals were resuscitated to a systolic blood pressure of 80 mm Hg with lactated Ringer according to the Tactical Combat Casualty Care Guidelines for 72 hours, after which packed red blood cells were transfused to simulate evacuation to higher levels of care. RESULTS The DP-VPA group needed significantly (p = 0.002) less volume of lactated Ringer to reach and maintain the target systolic blood pressure. This would translate to a 4.3 L volume sparing effect for a 70-kg person. CONCLUSION Addition of a single dose of VPA significantly decreases the volume of resuscitation required in a p-DCR model.

Original languageEnglish (US)
Pages (from-to)752-760
Number of pages9
JournalJournal of Trauma and Acute Care Surgery
Volume89
Issue number4
DOIs
StatePublished - Oct 1 2020
Externally publishedYes

Keywords

  • DCR
  • Dried plasma
  • VPA
  • plasma
  • swine

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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