{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T03:14:24Z","timestamp":1779074064271,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":126,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K15870"],"award-info":[{"award-number":["17K15870"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Emergency Medicine International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Purpose:<\/jats:bold>\n                    Peripheral intravenous catheter (PIVC)\u2013administered noradrenaline offers faster treatment for septic shock but risks complications like phlebitis. We aimed to investigate the relationship between the total noradrenaline dose administered via PIVCs and the development of phlebitis by considering the influence of noradrenaline as a time\u2010dependent covariate.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    A post hoc analysis was conducted on prospective multicenter cohort data from 23 intensive care units in Japan. The total noradrenaline dose was included as a time\u2010dependent variable in a multilevel Cox regression model, and smoothing splines assessed nonlinear relationships. The primary endpoint was phlebitis. Directed acyclic graphs were used to define confounding factors for the analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The analysis included 3410 PIVCs from 1351 patients, with noradrenaline administered to 70 patients (5.2%) with 91 PIVCs (2.6%). The median dwell time and interquartile range of PIVCs was 46.2\u2009h (21.3\u201382.9). No significant association was observed between the total noradrenaline dose and the occurrence of phlebitis through analysis using the multilevel Cox regression model with time\u2010dependent covariate, which assumed the linear relationship between phlebitis occurrence and the total noradrenaline dose (hazard ratio 1.06, 95% confidence interval [CI] 0.93\u20131.20). Spline curve analysis suggested a nonlinear relationship between the total noradrenaline dose and phlebitis, and the risk of phlebitis increased when the total administered dose of noradrenaline exceeded 6\u2009mg as the lower limit of the 95% CI exceeded the significant threshold of 1.0. Sensitivity analyses, including additional potential risk factors, showed consistent results compared with those of the primary analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Administering noradrenaline within a total dose not exceeding 6\u2009mg reduces the risk of phlebitis, potentially allowing safer administration through PIVCs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    UMIN Clinical Trials Registry (UMIN\u2010CTR): UMIN000028019\n                  <\/jats:p>","DOI":"10.1155\/emmi\/4457109","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T03:34:25Z","timestamp":1746588865000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Noradrenaline Administration Dosage on the Occurrence of Peripheral Intravenous Catheter\u2013Related Venous Phlebitis in Critically Ill Patients Using a Time\u2010Dependent Multilevel Cox Regression Model"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-1595","authenticated-orcid":false,"given":"Hideto","family":"Yasuda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6341-7415","authenticated-orcid":false,"given":"Claire M.","family":"Rickard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-9519","authenticated-orcid":false,"given":"Jessica 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