{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:52:02Z","timestamp":1791582722628,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T00:00:00Z","timestamp":1415232000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"United States Air Force Office of the Surgeon General","award":["FWH20100172A"],"award-info":[{"award-number":["FWH20100172A"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Academic Emergency Medicine"],"published-print":{"date-parts":[[2014,11]]},"abstract":"Abstract<\/jats:title>Objectives<\/jats:title>Tricyclic antidepressants (TCA<\/jats:styled-content>s) are highly lipophilic medications used to treat posttraumatic stress disorder and chronic pain. Intravenous lipid emulsion (ILE<\/jats:styled-content>) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE<\/jats:styled-content> has been studied in TCA<\/jats:styled-content> overdose in small animals, and cases are reported in humans, but controlled studies in a larger animal model are lacking. Given the high lipophilicity of amitriptyline, a TCA<\/jats:styled-content>, the hypothesis was that ILE<\/jats:styled-content> would be more effective than the standard antidote sodium bicarbonate in improving amitriptyline\u2010induced hypotension. The objective was to determine if ILE<\/jats:styled-content> improved hypotension (defined by a mean arterial pressure [MAP<\/jats:styled-content>]\u00a0<\u00a060% baseline) compared to sodium bicarbonate for amitriptyline overdose in a critically ill porcine model.<\/jats:p><\/jats:sec>Methods<\/jats:title>In this prospective, randomized, controlled trial, 24 female Sus scrofa<\/jats:italic> swine weighing 45 to 55\u00a0kg were infused with amitriptyline at 0.5\u00a0mg\/kg\/min until the MAP reached 60% of baseline values. Animals were randomized to the experimental treatment group (ILE 7 mL<\/jats:styled-content>\/kg bolus, then 0.25 mL<\/jats:styled-content>\/kg\/min) or the standard treatment group (sodium bicarbonate 2 mE<\/jats:styled-content>q\/kg plus an equal volume of saline). The primary outcome was a 50% improvement in MAP after ILE administration. We continuously monitored heart rate (HR), systolic blood pressure (sBP<\/jats:styled-content>), MAP, and cardiac output. Electrocardiograms were recorded every 15 minutes. Serum pH<\/jats:styled-content>, pCO<\/jats:styled-content>2<\/jats:sub>, bicarbonate, lactate, and electrolytes were measured. Amitriptyline levels were measured by liquid chromatography\/tandem mass spectrometry. Statistical methods used to detect a difference in MAP between the two treatment groups included repeated\u2010measures analysis of variance, adjusted for treatment, time, and the interaction of treatment by time. A sample size of 12 animals per group provided a power of 0.8 and an alpha of 0.05 to detect a 50% difference in MAP.<\/jats:p><\/jats:sec>Results<\/jats:title>There was no difference at baseline between ILE and sodium bicarbonate groups in mean HR, sBP<\/jats:styled-content>, MAP, or cardiac output. Mean amounts of amitriptyline to reach hypotension and time to hypotension were similar between groups. After hypotension there was no difference between groups for mean HR, sBP<\/jats:styled-content>, MAP, or cardiac output. The median time from hypotension to death was greater for the sodium bicarbonate group (10\u00a0minutes [IQR\u00a0= 6 to 61\u00a0minutes] vs. 5\u00a0minutes [IQR\u00a0= 4.5 to 6\u00a0minutes] for the ILE group; p\u00a0=\u00a00.003), but overall survival was not different. One ILE and four sodium bicarbonate pigs survived. Additionally, no difference was detected in QRS intervals between the two groups. The mean (\u00b1SD) amitriptyline level in the lipid layer was 3.34 (\u00b12.12) \u03bcg\/mL<\/jats:styled-content>, and in the aqueous layer, 4.69 (\u00b12.44) \u03bcg\/mL<\/jats:styled-content>. The ILE fatty layer contained 38.2% of total measurable amitriptyline, while the aqueous layer contained 53.6%.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Intravenous lipid emulsion treatment failed to improve amitriptyline\u2010induced hypotension when compared to the standard treatment of sodium bicarbonate in a large animal model of severe TCA<\/jats:styled-content> overdose. Larger groups with better survival may yield different results from the high mortality observed in this pilot study. Similar amounts of amitriptyline were found in the aqueous and lipid layers. These conclusions are limited to a single ILE<\/jats:styled-content> regimen.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acem.12513","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T17:45:30Z","timestamp":1415295930000},"page":"1212-1219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model"],"prefix":"10.1111","volume":"21","author":[{"given":"Shawn M.","family":"Varney","sequence":"first","affiliation":[{"name":"The Department of Emergency Medicine San Antonio Military Medical Center San Antonio TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikhyat S.","family":"Bebarta","sequence":"additional","affiliation":[{"name":"The Department of Medical Toxicology San Antonio Military Medical Center San Antonio TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni E.","family":"Vargas","sequence":"additional","affiliation":[{"name":"The Office of the Chief Scientist\/59th MDW Wilford Hall Ambulatory Surgical Center San Antonio TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Boudreau","sequence":"additional","affiliation":[{"name":"The Department of Emergency Medicine San Antonio Military Medical Center San Antonio TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Castaneda","sequence":"additional","affiliation":[{"name":"The Department of Emergency Medicine San Antonio Military Medical Center San Antonio TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-7241-18-51"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1553-2712.2009.00499.x"},{"key":"e_1_2_8_4_1","unstructured":"Association of Anaesthetists of Great Britain and Ireland.AAGBI Safety Guideline: Management of Severe Local Anaesthetic Toxicity. Available at:http:\/\/www.aagbi.org\/sites\/default\/files\/la_toxicity_2010_0.pdf. Accessed Aug 9 2014."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2006.07.016"},{"issue":"1","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"S177","DOI":"10.1197\/j.aem.2006.03.448","article-title":"Hemodynamic effect of intralipid in amitriptyline toxicity [abstract]","volume":"13","author":"Bania TC","year":"2006","journal-title":"Acad Emerg Med"},{"key":"e_1_2_8_7_1","first-page":"30","article-title":"A lipid emulsion reduces mortality from clomipramine overdose in rats","volume":"44","author":"Yoav G","year":"2002","journal-title":"Vet Hum Toxicol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650701226192"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(85)80725-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-6757(94)90060-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-6757(88)90241-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1984.tb02142.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2011.00826.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4141\/A03-123"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-2511"},{"key":"e_1_2_8_16_1","first-page":"460","article-title":"Lipid emulsion in massive imipramine overdose","volume":"47","author":"Al\u2010Duaij N","year":"2009","journal-title":"Clin Toxicol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819b5261"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/195483"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318240d8e7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2011.06.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.06.017"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2010.04.009"},{"key":"e_1_2_8_23_1","volume-title":"Goldfrank's Toxicologic Emergencies","author":"Bania TC","year":"2011"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-6757(86)90155-5"},{"key":"e_1_2_8_25_1","first-page":"351","article-title":"The pig as a model for myocardial ischemia and exercise","volume":"36","author":"White F","year":"1986","journal-title":"Lab Anim Sci"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1553-2712.2008.00313.x"}],"container-title":["Academic Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facem.12513","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acem.12513","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acem.12513","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acem.12513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T19:12:40Z","timestamp":1695496360000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acem.12513"}},"subtitle":[],"editor":[{"given":"James E.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,11]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/acem.12513"],"URL":"https:\/\/doi.org\/10.1111\/acem.12513","archive":["Portico"],"relation":{},"ISSN":["1069-6563","1553-2712"],"issn-type":[{"value":"1069-6563","type":"print"},{"value":"1553-2712","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11]]},"assertion":[{"value":"2014-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}