{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:41:28Z","timestamp":1792788088208,"version":"4.5.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007432","name":"odd berg medical research foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007432","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004102","name":"laerdal foundation for acute medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004102","id-type":"DOI","asserted-by":"publisher"}]},{"name":"institutt til fremme av anestesiologisk forskning"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Scand J Trauma Resusc Emerg Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tranexamic acid (TXA) reduce mortality in bleeding trauma patients, with greater effect if administered early. Serum concentrations above 10\u00a0\u00b5g\/mL are considered sufficient to inhibit fibrinolysis. Normally administered intravenously (i.v.), TXA can also be administered intramuscularly (i.m.). This could be advantageous in low resource and military settings, if sufficient serum concentrations can be reached in shocked patients with reduced muscular blood perfusion. Accordingly, we aimed to: (1) Determine the impact of shock on the pharmacokinetics of i.m. TXA, and (2) Compare the pharmacokinetics of i.v. versus i.m. TXA in ongoing shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>In a prospective experimental study, N\u2009=\u200918 Norwegian landrace pigs (40\u201350\u00a0kg), utilised in a surgical course in haemostatic emergency surgery, were subjected to various abdominal and thoracic trauma. After 1\u00a0h of surgery the animals were given 15\u00a0mg\/kg TXA either i.v. or i.m. A control group without injury, or surgery, received intramuscular TXA. Blood samples were drawn at 0, 5, 15, 25, 35, 45, 60 and 85\u00a0min. The samples were centrifuged and analysed with liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) for TXA serum-concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In shocked pigs, i.m. administration resulted in a mean maximum serum concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) of 20.9\u00a0\u00b5g\/mL, and i.v. administration a C\n                      <jats:sub>max<\/jats:sub>\n                      of 48.1\u00a0\u00b5g\/mL. C\n                      <jats:sub>max<\/jats:sub>\n                      occurred 15\u00a0min after i.m. administration and 5\u00a0min after i.v. administration. In non-shocked swine, i.m. administration resulted in a C\n                      <jats:sub>max<\/jats:sub>\n                      of 36.9\u00a0\u00b5g\/mL after 15\u00a0min. In all groups, mean TXA serum concentrations stayed above 10\u00a0\u00b5g\/mL from administration to end of experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>I.m. administration of TXA in shocked pigs provides serum concentrations associated with inhibition of fibrinolysis. It may be an alternative to i.v. and intraosseous administration during stabilisation and transport of trauma patients to advanced medical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13049-021-00983-2","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T06:14:26Z","timestamp":1639808066000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intramuscular uptake of tranexamic acid during haemorrhagic shock in a swine model"],"prefix":"10.1186","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-8909","authenticated-orcid":false,"given":"H\u00e5kon Kv\u00e5le","family":"Bakke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Martin","family":"Fuskev\u00e5g","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Waage","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Sveberg","family":"Dietrichs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"983_CR1","doi-asserted-by":"crossref","unstructured":"CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23\u201332.","DOI":"10.1016\/S0140-6736(10)60835-5"},{"key":"983_CR2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1055\/s-2007-996127","volume":"23","author":"S Okamoto","year":"1997","unstructured":"Okamoto S, Hijikata-Okunomiya A, Wanaka K, Okada Y, Okamoto U. Enzyme-controlling medicines: Introduction. Semin Thromb Hemost. 1997;23:493\u2013501.","journal-title":"Semin Thromb Hemost"},{"key":"983_CR3","doi-asserted-by":"publisher","first-page":"731","DOI":"10.2460\/ajvr.75.8.731","volume":"75","author":"DJ Fletcher","year":"2014","unstructured":"Fletcher DJ, Blackstock KJ, Epstein K, Brainard BM. Evaluation of tranexamic acid and \u03b5-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans. Am J Vet Res. 2014;75:731\u20138.","journal-title":"Am J Vet Res"},{"key":"983_CR4","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1213\/ANE.0b013e3182a22258","volume":"117","author":"BE Yee","year":"2013","unstructured":"Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg. 2013;117:767\u201372.","journal-title":"Anesth Analg"},{"key":"983_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/MBC.0000000000000789","volume":"30","author":"R Picetti","year":"2019","unstructured":"Picetti R, Shakur-Still H, Medcalf RL, Standing JF, Roberts I. What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies. Blood Coagul Fibrinolysis. 2019;30:1\u201310.","journal-title":"Blood Coagul Fibrinolysis"},{"key":"983_CR6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0140-6736(17)32455-8","volume":"391","author":"A Gayet-Ageron","year":"2018","unstructured":"Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I, et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018;391:125\u201332.","journal-title":"Lancet"},{"key":"983_CR7","doi-asserted-by":"crossref","unstructured":"CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. 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