{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T19:01:10Z","timestamp":1780254070157,"version":"3.54.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Palliat Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Terminally ill patients often have difficulty taking medications. Suitable, minimally invasive, fast-acting administration routes are particularly important. Trials on alternative drug administration routes in palliative care are essential to base therapy decisions on evidence rather than experience.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>To evaluate the effectiveness of intranasal compared with subcutaneous midazolam for the initial management of terminal agitation in palliative care patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Randomized, investigator-initiated open-label phase-II trial, August 2022\u2013July 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting\/Participants:<\/jats:title>\n                    <jats:p>\n                      Monocentric trial at the palliative care ward of a German University Hospital. 180 patients were assessed for suitability, 60 patients (median age, 68\u2009years (SD 12.3), 26 female) were randomized 1:1 and analyzed. Patients with terminal agitation fulfilling all eligibility criteria were randomized to midazolam 5\u2009mg administered either intranasal (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200930) or subcutaneous (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200930). Primary outcome: Improvement of terminal agitation by midazolam administration assessed by RASS-PAL-score. Secondary outcome: Midazolam plasma concentrations after administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Median RASS-PAL-scores decreased significantly in both groups. Intranasal group: 2 at baseline, to \u20131 at 5\u2009min and \u20132 at 20\u2009min. Subcutaneous group: 1,\u20130 and \u20131. Within-group reductions exceeded the clinically relevant threshold of \u2a7e 1 point at 5 and 20\u2009min (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Median midazolam plasma concentrations were significantly higher intranasal (5\u2009min: 90\u2009ng\/ml, 20\u2009min: 83\u2009ng\/ml) than subcutaneous (5\u2009min: 15\u2009ng\/ml, 20\u2009min: 24\u2009ng\/ml). No patients withdrawn due to adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Midazolam intranasal administration was effective in reducing terminal agitation and achieves higher plasma concentrations compared to subcutaneous administration. It is an alternative route of application to improve end-of-life care for terminally ill patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration:<\/jats:title>\n                    <jats:p>\n                      MinTU Study 173-01, Eudra CT No.: 2021-004789-36, DRKS ID: 00026775 (07.07.2022,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/drks.de\/search\/de\/trial\/DRKS00026775\">https:\/\/drks.de\/search\/de\/trial\/DRKS00026775<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  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