Delirium and adverse clinical outcomes: a matched cohort study in the UK Biobank

Abstract

Background: Delirium complicates up to one in four hospitalisations among older adults, but its clinical sequelae beyond cognitive impairment, functional decline, and mortality are not well characterised. Whether delirium signals broader multisystem vulnerability leading to later adverse outcomes remains uncertain. We aimed to examine the association of in-hospital delirium with the occurrence of a range of adverse outcomes during later hospitalisations in the UK.

Methods: We performed a matched cohort study among hospitalised UK Biobank participants recruited in England, Scotland, and Wales in 2006-10 with linked hospital inpatient records collected from Jan 1, 1997 to Oct 31, 2022. We matched 14 909 individuals with delirium (1:1) to hospitalised control individuals without delirium by age, sex, Hospital Frailty Risk Score, primary diagnosis, episode length of stay, and intensive care unit length of stay of the index episode. The primary outcome was the risk of adverse clinical outcomes following delirium. Delirium was identified by ICD-10 codes, with exposure intensity defined as the number of episodes within 12 months of the index admission. Adverse clinical outcomes were selected based on existing literature and included incident events occurring during subsequent hospitalisations: falls, fractures (any and hip), pressure injury, urinary and faecal incontinence, myocardial infarction, heart failure, stroke, venous thromboembolism, pulmonary embolism, acute kidney injury, gastrointestinal bleeding, pneumonia, and sepsis. Fine-Gray subdistribution hazard models accounted for death as a competing risk and adjusted for socioeconomic covariates.

Findings: Over a maximum follow-up of 26 years, the median time to event was 1·2 years (IQR 0·2-3·3) in the delirium group and 1·3 years (0·3-3·6) in the control group. Delirium was associated with a higher risk of 12 of the 15 adverse clinical outcomes than no delirium, which were urinary incontinence (subdistribution hazard ratio 2·01 [95% CI 1·78-2·28]), falls (1·96 [1·78-2·17]), pressure injury (1·72 [1·53-1·93]), acute kidney injury (1·71 [1·57-1·86]), sepsis (1·67 [1·52-1·84]), hip fracture (1·66 [1·39-2·00]), stroke (1·62 [1·41-1·87]), overall fractures (1·56 [1·40-1·74]), pneumonia (1·53 [1·41-1·65]), faecal incontinence (1·53 [1·31-1·78]), heart failure (1·31 [1·18-1·45]), and gastrointestinal bleeding (1·23 [1·09-1·38]). Each additional episode was associated with a 6-17% higher risk. Findings were consistent across sensitivity analyses excluding individuals with short follow-up, those with prevalent dementia, and the least well-matched pairs.

Interpretation: In-hospital delirium was consistently and dose-responsively associated with a range of adverse outcomes, independent of frailty and pre-existing dementia, supporting its recognition as a sentinel event indicating longer-term vulnerability.

Funding: Sigrid Jusélius Foundation, the Osk Huttunen Foundation, the Biomedicum Helsinki Foundation, and Finska Läkaresällskapet.