BackgroundBlood urea nitrogen (BUN) levels had been reported to be Linked to the prognosis of critically ill patients. The purpose of this study is to investigate the association of the BUN trajectories with 28-day mortality risk in sepsis-associated delirium (SAD) patients. MethodsThis retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Latent class trajectory modeling (LCTM) was employed to identify subclasses of BUN trajectories within the first six days after ICU admission in patients with SAD. Cox regression models were utilized to assess the association between baseline BUN levels at ICU admission, as well as BUN trajectories, and the risk of 28-day mortality. Kaplan-Meier (K-M) survival curves were used to compare the survival differences between the trajectories. ResultsAmong 2,626 SAD patients enrolled, 574 (21.86%) died within 28 days. The median BUN levels of patients were 20 (14, 31) mg/dL. The levels of BUN at ICU admission exhibited a non-linear positive correlation with 28-day mortality (P overall < 0.001, P non-linearity < 0.001). The BUN trajectories were classified into 4 classes: Class 1 exhibited stable normal BUN levels, with slight fluctuations between 20 mg/dL. Class 2 had a moderate initial BUN level (40 mg/dL), showed a slow increase, and then rapidly decreased. Class 3 had a moderate initial BUN level (50 mg/dL), showed a slow decrease, and then rapidly increased. Class 4 had a moderate initial BUN level (40 mg/dL) and showed a consistent increase. Compared with Class 1, Class 2 was not associated with an increased risk of 28-day mortality (P = 0.665), Class 3 (HR = 1.70, 95% CI: 1.27-2.28) and Class 4 (HR = 1.47, 95% CI: 1.19-1.81) were related to an increased risk of 28-day mortality. Subgroup analysis demonstrated that in SAD patients without severe liver disease, Class 4 was associated with a higher risk of 28-day mortality in different population subgroups (P < 0.05). ConclusionsHeterogeneity in BUN trajectories among SAD patients was associated with 28-day mortality risk. Moderate initial BUN levels showed consistent increase trend trajectories were an important risk factor for 28-day mortality.