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

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Original Publication: Oxford, UK : Wiley-Blackwell, c2008-

Delirium*/blood ; Delirium*/epidemiology ; Delirium*/genetics ; Delirium*/diagnosis ; Mendelian Randomization Analysis* ; Critical Illness* ; Blood Urea Nitrogen*; Humans ; Retrospective Studies ; Aged ; Male ; Female ; Aged, 80 and over ; Risk Factors

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.
(© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Crit Care Med. 2013 Jan;41(1):263-306. (PMID: 23269131)
J Neurol. 2023 Oct;270(10):4608-4616. (PMID: 37517039)
Lipids Health Dis. 2024 Jun 3;23(1):164. (PMID: 38831466)
J Clin Anesth. 2016 Sep;33:507-13. (PMID: 26604015)
Neurotherapeutics. 2023 Oct;20(6):1565-1591. (PMID: 37759139)
Med Care. 2018 Oct;56(10):890-897. (PMID: 30179988)
Int J Epidemiol. 2015 Apr;44(2):512-25. (PMID: 26050253)
Front Cardiovasc Med. 2023 Jul 31;10:1189884. (PMID: 37583584)
J Neurol. 2019 Dec;266(12):3065-3075. (PMID: 31520105)
Lancet. 2014 Mar 8;383(9920):911-22. (PMID: 23992774)
Mol Neurobiol. 2024 Nov;61(11):8640-8655. (PMID: 38532242)
Neuropsychiatr Dis Treat. 2013;9:1359-70. (PMID: 24092976)
Nat Rev Neurol. 2009 Apr;5(4):210-20. (PMID: 19347026)
Genet Epidemiol. 2013 Nov;37(7):658-65. (PMID: 24114802)
Genet Epidemiol. 2016 May;40(4):304-14. (PMID: 27061298)
Infect Dis Ther. 2023 Oct;12(10):2353-2366. (PMID: 37751020)
Sci Data. 2023 Jan 3;10(1):1. (PMID: 36596836)
Int J Surg. 2021 Sep;93:106063. (PMID: 34411752)
Crit Care Med. 2018 Sep;46(9):e825-e873. (PMID: 30113379)
Sci Rep. 2023 Nov 13;13(1):19834. (PMID: 37964009)
J Intensive Care. 2024 Feb 20;12(1):8. (PMID: 38378667)
JAMA. 2001 Dec 5;286(21):2703-10. (PMID: 11730446)
Lancet. 2007 Oct 20;370(9596):1453-7. (PMID: 18064739)
Front Psychiatry. 2022 Apr 08;13:851104. (PMID: 35463531)
Cureus. 2016 May 02;8(5):e596. (PMID: 27382523)
Nephron Clin Pract. 2012;120(4):c179-84. (PMID: 22890468)
J Clin Med. 2022 Nov 13;11(22):. (PMID: 36431186)
J Clin Med. 2024 Feb 06;13(4):. (PMID: 38398245)
Cancer Res Treat. 2024 Oct;56(4):1277-1287. (PMID: 38419423)
Ann Transl Med. 2017 Jan;5(1):7. (PMID: 28164092)
Clin Hemorheol Microcirc. 2018;69(1-2):123-131. (PMID: 29758935)
Am J Respir Crit Care Med. 2017 Jun 15;195(12):1597-1607. (PMID: 27854517)
N Engl J Med. 2018 Jan 4;378(1):96-97. (PMID: 29298149)
Nature. 2023 Jan;613(7944):508-518. (PMID: 36653562)
Int J Mol Sci. 2022 Dec 30;24(1):. (PMID: 36614132)
Hum Mol Genet. 2014 Sep 15;23(R1):R89-98. (PMID: 25064373)
Kidney Int. 2014 Nov;86(5):923-31. (PMID: 24940796)
Front Cardiovasc Med. 2022 Nov 10;9:967614. (PMID: 36440028)
Nat Med. 2007 Oct;13(10):1176-84. (PMID: 17828273)
Eur Heart J. 2014 Nov 14;35(43):3021-32. (PMID: 24658767)
Ann Am Thorac Soc. 2019 Jan;16(1):22-28. (PMID: 30230362)
Ann Intensive Care. 2012 Dec 27;2(1):49. (PMID: 23270646)
Lipids Health Dis. 2024 Jul 25;23(1):227. (PMID: 39054513)
Front Aging Neurosci. 2021 Apr 30;13:626127. (PMID: 33994990)
Chem Sci. 2019 Dec 11;11(5):1307-1315. (PMID: 33209250)
Apoptosis. 2019 Oct;24(9-10):785-797. (PMID: 31309362)
Yonsei Med J. 2021 Jul;62(7):600-607. (PMID: 34164957)
Nutrients. 2021 Dec 15;13(12):. (PMID: 34960033)
Atherosclerosis. 2015 Apr;239(2):393-400. (PMID: 25682038)
IUBMB Life. 2018 Apr;70(4):267-275. (PMID: 29542227)
Sci Rep. 2021 Aug 26;11(1):17260. (PMID: 34446816)
Gen Hosp Psychiatry. 2015 Sep-Oct;37(5):408-13. (PMID: 26051015)
Intensive Care Med. 2015 Jun;41(6):1048-56. (PMID: 25894620)
Atherosclerosis. 2021 Sep;333:1-8. (PMID: 34390959)
Int J Cardiol. 2022 Sep 15;363:94-101. (PMID: 35777488)
J Clin Invest. 2010 Jan;120(1):203-13. (PMID: 19955654)
Front Endocrinol (Lausanne). 2022 Oct 27;13:985167. (PMID: 36387890)
Adv Biomed Res. 2023 Feb 25;12:40. (PMID: 37057249)

22ZYYLCCG05 Tianjin Medical University General Hospital Clinical Research Program; 2021-N-15-8 2021-N-15 project of China International Medical Foundation; TJWJ2024XK006 Tianjin Health Research Project; 24JRRCC00160 Tianjin Science and Technology Innovation Talent Training Project

Keywords: ICU‐CAM; MIMIC IV; delirium; elderly; encephalopathy; mendelian randomization; urea nitrogen

Date Created: 20250103 Date Completed: 20250106 Latest Revision: 20250108

20260130

PMC11702503

10.1111/cns.70201

39754021