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These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the <jats:styled-content style=\"fixed-case\">ICU<\/jats:styled-content>. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients.<\/jats:p>","DOI":"10.1002\/phar.2017","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T03:36:45Z","timestamp":1503373005000},"page":"1309-1321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult <scp>ICU<\/scp> Patients: A Literature Review with Practical Considerations"],"prefix":"10.1002","volume":"37","author":[{"given":"David J.","family":"Gagnon","sequence":"first","affiliation":[{"name":"Department of Pharmacy Maine Medical Center Portland Maine"},{"name":"Tufts University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-5720","authenticated-orcid":false,"given":"Gabriel V.","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Intermountain Medical Center Murray Utah"},{"name":"Neurosciences Institute Intermountain Healthcare Salt Lake City Utah"},{"name":"Pharmacotherapy University of Utah College of Pharmacy Salt Lake City Utah"},{"name":"Roseman University College of Pharmacy South Jordan Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Riker","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Neuroscience Institute Maine Medical Center Portland Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles L.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Maine Medical Center Portland Maine"},{"name":"Tufts University School of Medicine Boston Massachusetts"},{"name":"Department of Critical Care Medicine Neuroscience Institute Maine Medical Center Portland Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182783b72"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182a16898"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2016.05.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201512-2435CP"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885066615592348"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216100-00003"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467210902010095"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00075-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.11.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216100-00004"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198815060-00002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1984.tb05632.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1912"},{"key":"e_1_2_7_15_1","first-page":"1794","volume-title":"Goodman & Gilman's the pharmacological basis of therapeutics","author":"Brunton LL","year":"2006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.033878"},{"key":"e_1_2_7_17_1","volume-title":"Phenobarbital package insert","author":"West\u2010Ward Pharmaceutical Corp","year":"2011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.17.2.232"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.14080190"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2016.09.006"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psym.2015.09.008"},{"key":"e_1_2_7_22_1","unstructured":"National Library of Medicine.LiverTox. 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