Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 22;15(1):30937.
doi: 10.1038/s41598-025-14180-z.

Delirium as a mediating factor in the survival benefits of dexmedetomidine in acute brain injury management

Juan Wang #  1   2 , Jia-Qing Sun #  3   2 , Yue Lu #  3   2 , Qi-Lin Yang  4 , Peng-Lai Zhao  5   6 , Chun-Hua Hang  7   8   9 , Wei Li  10   11   12
Affiliations

Delirium as a mediating factor in the survival benefits of dexmedetomidine in acute brain injury management

Juan Wang et al. Sci Rep. .

Abstract

Acute brain injury (ABI) is a leading cause of ICU admission and mortality. Effective sedation is essential for preventing secondary brain injury, and dexmedetomidine has emerged as a potential neuroprotective agent. We conducted a retrospective analysis using the MIMIC-IV v3.1 database, including adult patients admitted to the ICU with ABI. Patients were divided into two groups based on whether they received dexmedetomidine. Propensity score matching (PSM), weighting methods, and doubly robust estimation were used to adjust for confounding factors. Results from the doubly robust analysis showed that dexmedetomidine use was significantly associated with reduced in-hospital mortality (HR: 0.41, 95% CI: 0.35-0.48, p < 0.001) and ICU mortality (HR: 0.34, 95% CI: 0.28-0.41, p < 0.001). Additionally, dexmedetomidine was associated with significantly increased vasopressor-free days (MD: 2.64, 95% CI: 1.98-3.30, p < 0.001) and ventilation-free days (MD: 2.23, 95% CI: 1.59-2.86, p < 0.001). Further mediation analysis indicated that delirium mediated 37% of the effect of dexmedetomidine on in-hospital mortality and 60% of its effect on ICU mortality. This suggests that delirium may be a key mediator of dexmedetomidine's beneficial effects, consistent with its potential advantages in sedation and neuroprotection observed in previous studies. In conclusion, dexmedetomidine use in ICU patients with ABI is associated with significantly lower mortality and improved clinical outcomes, with delirium acting as a critical mediator.

Keywords: Acute brain injury; Delirium; Dexmedetomidine; ICU; Mortality..

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was performed according to the guidelines of the Helsinki Declaration. The use of the MIMIC-IV database was approved by the review committee of Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center. The data is publicly available (in the MIMIC-IV database), therefore, the ethical approval statement and the requirement for informed consent were waived for this study.

Figures

Fig. 1
Fig. 1
Landmark Analysis of Dexmedetomidine Use and Mortality Outcomes. Landmark Kaplan-Meier survival curves starting from day 3 post-ICU admission for (A) in-hospital mortality and (B) ICU mortality, stratified by dexmedetomidine use. Survival probabilities (with 95% CI represented by shaded areas), numbers at risk at specified time intervals, and corresponding p-values are displayed. The landmark time (day 3) was selected based on previous literature.
Fig. 2
Fig. 2
Subgroup analysis of in-hospital and ICU mortality.Forest plots displaying HR and 95%CIsfor in-hospital mortality (red) and ICU mortality (blue) in subgroups from the matched cohort. Analyses included subgroups defined by age, sex, hypertension, diabetes, and craniotomy status.
Fig. 3
Fig. 3
Mediation Analysis of the Effect of Dexmedetomidine on Clinical Outcomes in ABI Through Delirium.Panel A shows a significant reduction in in-hospital mortality, with delirium mediating 37% of the effect. Panel B demonstrates a substantial reduction in ICU mortality, with delirium accounting for a 60% mediation effect. Panel C reveals a moderate 42% mediation effect on 28-day vasopressor-free probability, and Panel D indicates a 32% mediation effect on 28-day ventilation-free probability.
See this image and copyright information in PMC

References

    1. Wang, Y. et al. Burden of common neurologic diseases in Asian countries, 1990–2019: an analysis for the global burden of disease study 2019 [J]. Neurology100(21), e2141–e2154 (2023). - PMC - PubMed
    1. Oddo, M. et al. The neurological pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study . Lancet Neurol.22(10), 925–933 (2023). - PubMed
    1. Robba, C. et al. Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study . Lancet Neurol.20(7), 548–558 (2021). - PubMed
    1. Krishnamoorthy, V. et al. Multiorgan dysfunction after severe traumatic brain injury: epidemiology, mechanisms, and clinical management . Chest160(3), 956–964 (2021). - PMC - PubMed
    1. Dewan, M. C. et al. Estimating the global incidence of traumatic brain injury . J. Neurosurg.130(4), 1080–1097 (2019). - PubMed