Association Between Blood Urea Nitrogen and Delirium in Critically Ill Elderly Patients Without Kidney Diseases: A Retrospective Study and Mendelian Randomization Analysis

ABSTRACT Objective This study investigates the association between blood urea nitrogen (BUN) levels and the risk of delirium in critically ill elderly patients without kidney disease. Methods A retrospective analysis was conducted using data from the MIMIC‐IV database. The relationship between BUN and delirium risk was illustrated through the restricted cubic spline (RCS) method. Patients were stratified by BUN levels and examined for delirium incidence using logistic regression, subgroup analysis, and sensitivity analysis. Mendelian randomization (MR) was employed to explore potential causal relationships. Results The maximum BUN level exhibited the strongest non‐linear positive association with the odds of delirium. Compared to the Q1 group, both the Q3 (23–31 mg/dL) and Q4 (> 31 mg/dL) groups consistently showed increased odds of developing delirium. Subgroup analysis identified a significant interaction between BUN and midazolam, with the association only evident in patients not exposed to midazolam. After adjusting for baseline characteristics, the odds ratio for delirium was found to range from 1.35 to 1.39 in those with BUN levels exceeding 23 mg/dL. However, the MR analysis did not reveal any significant causal relationship (all p > 0.05). Conclusion In conclusion, elevated BUN may be a risk factor for delirium in critically ill elderly patients without renal dysfunction, with this potential link possibly modulated by midazolam exposure.