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This study aims to examine the associations of fentanyl versus morphine with delirium, length of stay (LOS) in the intensive care unit (ICU), and short-term mortality in this population. Clinical data from critically ill adults with malignancies admitted to the ICU for the first time were derived from the Medical Information Mart for Intensive Care-IV v3.1. The primary outcome was delirium. Secondary outcomes comprised 14- and 30-day all-cause mortality and the LOS in the ICU. Logistic regression models were adopted to evaluate the association of fentanyl versus morphine with delirium; linear regression models were applied to examine the association with the LOS in the ICU; Cox proportional hazards models were adopted to analyze associations with 14- and 30-day all-cause mortality. Subgroup analyses stratified by sex, age, hypertension, diabetes mellitus, and sepsis were performed to explore the stability of the findings. Propensity score matching was conducted for sensitivity analysis. Data from 2074 critically ill patients with malignancy (1051 fentanyl users and 1023 morphine users) were analyzed. Compared with those receiving fentanyl, patients receiving morphine demonstrated a significantly diminished risk of delirium (odds ratio\u2009=\u20090.273, 95% confidence interval [CI]: [0.200, 0.371],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Morphine was linked to a shorter LOS in the ICU relative to fentanyl (\u03b2\u2009=\u2009\u2212\u20090.870, 95% CI: \u2212\u20091.496 to \u2212\u20090.243,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007). Nonetheless, compared to fentanyl users, those receiving morphine were linked to a 114.60% elevated risk of 14-day all-cause mortality (hazard ratio [HR]\u2009=\u20092.146, 95% CI: [1.503, 3.066],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and a 70.60% heightened risk of 30-day all-cause mortality (HR\u2009=\u20091.706, 95% CI [1.254, 2.320],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In conclusion, morphine is associated with a diminished risk of delirium and a shorter LOS in the ICU among critically ill patients with malignancy, yet concurrently linked to elevated short-term mortality. These findings indicate potentially divergent outcome associations within this population and may offer a point of reference for individualized analgesic management in critically ill patients with malignancy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-62964-8","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T20:54:10Z","timestamp":1784408050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative outcomes of fentanyl and morphine in critically ill patients with malignancy: a retrospective cohort study utilizing MIMIC-IV"],"prefix":"10.1038","volume":"16","author":[{"given":"Huili","family":"Shui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenming","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingxue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"62964_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. 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