Validation of intraosseous delivery of valproic acid in a swine model of polytrauma

Ben E. Biesterveld*, Rachel O'Connell, Michael T. Kemp, Glenn K. Wakam, Aaron M. Williams, Manjunath P. Pai, Hasan B. Alam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background Intraosseous (IO) drug delivery may be necessary in emergency situations when intravenous access is unattainable. Valproic acid (VPA) is a histone deacetylase inhibitor that has previously been shown to improve survival in preclinical models of lethal polytrauma. In this study, we sought to compare serum levels of intravenously and IO-delivered VPA, and to analyze the effect of IO-delivered VPA. Methods Swine were subjected to 40% blood volume hemorrhage, brain injury, femur fracture, rectus crush injury and liver laceration. After 1 hour of shock, animals were randomized (n=3/group) to receive normal saline resuscitation (control), normal saline+intravenous VPA 150 mg/kg (intravenous group) or normal saline +IO VPA 150 mg/kg (IO group). Serum levels of VPA were assessed between groups, and proteomics analyses were performed on IO and control groups on heart, lung and liver samples. Results Intravenous and IO serum VPA levels were similar at 1, 3, 5 and 7 hours after starting the infusion (p>0.05). IO-delivered VPA induced significant proteomics changes in the heart, lung and liver, which were most pronounced in the lung. Biologic processes affected included inflammation, metabolism and transcriptional & translational machinery. The control group had 0% survival, and the intravenous and IO group both had 100% survival to the end of the experiment (p<0.05). Discussion IO-delivered VPA is noninferior to intravenous administration and is a viable option in emergent situations when intravenous access is unattainable. Level of evidence Not applicable (animal study).

Original languageEnglish (US)
Article numbere000683
JournalTrauma Surgery and Acute Care Open
Volume6
Issue number1
DOIs
StatePublished - Mar 17 2021

Keywords

  • brain injuries
  • hemorrhage
  • histone deacetylase inhibitors
  • proteomics
  • traumatic

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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