{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T06:10:01Z","timestamp":1758867001831,"version":"3.44.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The objective of this study is to assess the effect of subcutaneous treprostinil (TRE) administered peri\u2010operatively after Fontan operation on chest tube duration (CTD), hospital length of stay (LOS), and post\u2010operative hemodynamics. This is a single center randomized, blinded, placebo\u2010controlled study of pediatric patients with single ventricle congenital heart disease undergoing Fontan operation between September 2015 and September 2019. Patients were randomized to receive subcutaneous TRE (target dose 10\u2009ng\/kg\/min) or saline placebo starting intraoperatively through post\u2010operative day 7. Baseline demographics, pre\u2010operative hemodynamics, and peri\u2010operative clinical details were collected. The primary outcome was CTD. Secondary outcomes included hospital LOS and hemodynamics. Thirty\u2010four patients were randomized, 16 to TRE and 18 to saline placebo. Baseline characteristics were similar between groups, including pre\u2010operative hemodynamics. Patients receiving TRE had increased risk for longer CTD (median CTD 8 vs. 7 days compared to placebo [IQR: 7\u201312.5, 5\u20138 days, respectively] with a relative risk (RR) of 1.29 (95% CI: 1.02, 1.64; <jats:italic>p<\/jats:italic>\u2009=\u20090.03)) and increased risk for longer hospital LOS (median LOS 11 vs. 9 days compared to placebo [IQR: 9.5\u201314.5, 8\u201310 days, respectively] with a RR of 1.23 (95% CI: 1.00, 1.51; <jats:italic>p<\/jats:italic>\u2009=\u20090.05)). Patients receiving TRE had higher median Fontan pressure at post\u2010operative hour 12 (13\u2009mmHg [IQR: 12.5\u201315.0] vs. 10.5\u2009mmHg [IQR: 8.0\u201312.5]; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01 on repeated measure analysis model) and greater transpulmonary gradient at post\u2010operative hour 12 (7.0\u2009mmHg [IQR: 5.0\u20139.5] vs. 4.0\u2009mmHg [IQR: 3.5\u20135.0]; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01 on repeated measure analysis model) compared to placebo. Peri\u2010operative subcutaneous TRE did not reduce CTD or hospital LOS after Fontan operation and did not exert significant beneficial effects on post\u2010operative hemodynamics. Accordingly, TRE at a dose of 10\u2009ng\/kg\/min is not recommended for routine use in immediate post\u2010operative Fontan management.<\/jats:p>","DOI":"10.1002\/pul2.70122","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T04:29:57Z","timestamp":1752640197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Randomized, Placebo\u2010Controlled Trial of Peri\u2010Operative Treprostinil in Pediatric Patients Undergoing the Fontan Operation"],"prefix":"10.1002","volume":"15","author":[{"given":"Rachel T.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"},{"name":"Current Affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center Monroe Carrell Jr Children's Hospital Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4114-599X","authenticated-orcid":false,"given":"Stephanie S.","family":"Handler","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa A.","family":"Arunamata","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle T.","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Lu","sequence":"additional","affiliation":[{"name":"Quantitative Sciences Unit Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6259-7813","authenticated-orcid":false,"given":"Elisabeth","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra","family":"Ramamoorthy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peri\u2010operative, and Pain Medicine Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Kameny","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Stanford University Medical Center Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.26.3.240"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezu015"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.10.003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004515"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(97)70020-5"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.02.073"},{"issue":"9","key":"e_1_2_12_8_1","article-title":"Pharmacological Control of Pulmonary Blood Flow With Inhaled Nitric Oxide After the Fenestrated Fontan Operation","volume":"94","author":"Goldman A. 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