{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T17:40:03Z","timestamp":1756057203055,"version":"3.44.0"},"reference-count":46,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["F32GM130010"],"award-info":[{"award-number":["F32GM130010"]}]},{"name":"Frederick A. Coller Society Surgical Research Fellowship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Trauma Surg Acute Care Open"],"accepted":{"date-parts":[[2021,2,28]]},"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Intravenous and IO serum VPA levels were similar at 1, 3, 5 and 7 hours after starting the infusion (p&gt;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 &amp; 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&lt;0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>IO-delivered VPA is noninferior to intravenous administration and is a viable option in emergent situations when intravenous access is unattainable.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Level of evidence<\/jats:title>\n                  <jats:p>Not applicable (animal study).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/tsaco-2021-000683","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T12:21:42Z","timestamp":1615983702000},"page":"e000683","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Validation of intraosseous delivery of valproic acid in a swine model of polytrauma"],"prefix":"10.1136","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-7904","authenticated-orcid":false,"given":"Ben E","family":"Biesterveld","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Department of Surgery, Northwestern University, Evanston, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-9554","authenticated-orcid":false,"given":"Glenn 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