{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:34:34Z","timestamp":1786440874385,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005302","name":"Onassis Foundation","doi-asserted-by":"publisher","award":["OF 010\/C\u2019 CYCLE\u201d"],"award-info":[{"award-number":["OF 010\/C\u2019 CYCLE\u201d"]}],"id":[{"id":"10.13039\/501100005302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Midazolam is widely used as a pediatric premedication, but evidence from direct comparisons of oral and sublingual administration in children with congenital heart disease remains limited, particularly that from pharmacokinetic and physiologic data analyzed together. Methods: We conducted a single-center prospective randomized study comparing oral midazolam 0.5 mg\/kg with sublingual midazolam 0.3 mg\/kg in children undergoing cardiac surgery or catheterization procedures under general anesthesia. Plasma midazolam and 1-hydroxymidazolam concentrations were measured approximately 30 min after administration. Log-transformed concentrations were compared using regression\/ANCOVA models adjusted for dose and age. Changes in mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were analyzed from baseline to 15 and 30 min. Behavioral outcomes included the sedation score, separation from parents, and mask acceptance. Results: Sixty-eight children were randomized; 65 had evaluable pharmacokinetic samples and formed the complete-case pharmacokinetic cohort. Adjusted plasma midazolam concentrations did not differ significantly between the groups, with an adjusted geometric mean ratio for sublingual versus oral administration of 0.98 (95% CI 0.53\u20131.79; unadjusted p = 0.940; Holm-adjusted p = 1.000). The corresponding ratio for 1-hydroxymidazolam was 1.37 (95% CI 0.55\u20133.41; unadjusted p = 0.494; Holm-adjusted p = 1.000). HR and SpO2 changes were non-significant between the groups. At 30 min, sublingual administration was associated with a lower adjusted change in MAP compared with oral administration (adjusted difference \u221212.08 mmHg, 95% CI \u221219.74 to \u22124.42; unadjusted p = 0.002, Holm-adjusted p = 0.012). Behavioral outcomes did not differ significantly between the groups. Conclusions: In this prospective randomized pediatric cardiac cohort, oral midazolam 0.5 mg\/kg and sublingual midazolam 0.3 mg\/kg produced comparable plasma concentrations and similar behavioral outcomes. Sublingual administration was not associated with worse HR or SpO2 responses, although an isolated lower MAP change at 30 min warrants confirmation in larger studies. Sublingual midazolam may represent a feasible lower-dose alternative for premedication in this population.<\/jats:p>","DOI":"10.3390\/children13081067","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"1067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Premedication of Pediatric Cardiac Population with Midazolam: Comparison of Oral and Sublingual Administration Regarding Plasma Midazolam Concentration, Clinical Effectiveness, Hemodynamic and Behavioral Outcomes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-1836","authenticated-orcid":false,"given":"Theofili","family":"Kousi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-7020","authenticated-orcid":false,"given":"Afroditi","family":"Karafotia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-9677","authenticated-orcid":false,"given":"Vlasios","family":"Karageorgos","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-9941","authenticated-orcid":false,"given":"Georgios","family":"Gkantinas","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Sofianidou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9708-0523","authenticated-orcid":false,"given":"Meletios","family":"Kanakis","sequence":"additional","affiliation":[{"name":"Department of Congenital Cardiac Surgery, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Smina","sequence":"additional","affiliation":[{"name":"Center for Clinical, Experimental Surgery and Translational Research, Pharmacology-Pharmacotechnology, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6341-4495","authenticated-orcid":false,"given":"Ioanna","family":"Zergioti","sequence":"additional","affiliation":[{"name":"School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Tamvakopoulos","sequence":"additional","affiliation":[{"name":"Center for Clinical, Experimental Surgery and Translational Research, Pharmacology-Pharmacotechnology, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theofani","family":"Antoniou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Onassis Hospital Athens, 17674 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/IO9.0000000000000262","article-title":"Preoperative anxiety in children: Prevention and management. 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