In a compelling new study published in BMC Psychiatry, researchers have uncovered a significant association between nicotine dependence and the occurrence of delirium in patients admitted to intensive care units (ICUs). This groundbreaking retrospective cohort analysis leveraged the extensive MIMIC-IV v3.1 clinical database, bringing fresh insights into how nicotine dependence alters the risk landscape for critically ill patients.
Delirium, a complex neuropsychiatric syndrome characterized by acute cognitive dysfunction and fluctuating mental status, poses a substantial challenge in ICUs worldwide. Despite advances in intensive care medicine, delirium adversely affects patient outcomes, prolonging hospital stays and increasing mortality rates. While prior research has hinted at nicotine use as a modifiable risk factor, evidence directly linking nicotine dependence (ND) to delirium in critical care settings has been sparse and inconclusive until now.
The investigative team selected adult ICU patients from the MIMIC-IV database, ensuring each subject had documented delirium assessments and an ICU stay exceeding 24 hours. Stringent exclusion criteria were applied, omitting individuals with confounding neuropsychiatric conditions such as schizophrenia, dementia, depression, alcohol abuse, and cerebrovascular diseases. This careful curation resulted in a cohort of 24,043 patients, of whom 2,662 (approximately 11%) were identified as nicotine-dependent.
To address potential confounding variables and improve comparability between ND and non-ND groups, the researchers employed rigorous 1:1 propensity score matching. This statistical approach balanced baseline characteristics, creating comparable groups to isolate the effect of nicotine dependence on delirium risk. Analysis revealed that patients with nicotine dependence exhibited a notably higher incidence of ICU delirium, with rates of 30.8% versus 27.2% in non-dependent individuals—a statistically significant difference.
Further reinforcing these findings, multivariate Cox proportional hazards models and competing risk analyses established nicotine dependence as an independent predictor of delirium onset. These models, robust to multiple confounders and competing events such as mortality, highlighted the increased hazard that ND patients face regarding acute cognitive impairment during critical illness. Notably, the elevated delirium risk did not translate into significant differences in ICU or in-hospital mortality, nor in lengths of ICU or hospital stay, suggesting specific vulnerability to delirium without broad mortality implications within this cohort.
Sensitivity analyses and subgroup evaluations added layers of validation, confirming that the association remained consistent across different diagnostic coding versions and in varied patient subsets. The study also explored the impact of nicotine replacement therapy (NRT)—a treatment strategy for tobacco dependence—but these analyses suggested no substantial modification of delirium risk attributable to NRT in the ICU setting.
Mechanistically, nicotine’s chronic effects on neurotransmission, cerebral blood flow, and neuroinflammation may underlie the increased susceptibility to delirium observed in dependent individuals. Nicotine’s modulation of cholinergic pathways, which are crucial in attention and cognition, might exacerbate the already precarious neurological status of critically ill patients. Furthermore, withdrawal phenomena in the ICU, where smoking is impossible, could contribute to neuropsychiatric instability, precipitating delirium episodes.
Clinically, these findings carry profound implications. Delirium prevention strategies in ICU protocols could be notably enhanced by incorporating targeted screening for nicotine dependence upon admission. Early identification could trigger tailored interventions—ranging from nicotine withdrawal management to vigilant neurocognitive monitoring—to mitigate delirium incidence and improve patient outcomes. This approach aligns with a precision medicine paradigm, emphasizing individualized risk profiling and proactive care.
Moreover, the study sheds light on an underappreciated yet modifiable risk factor within critical care environments. While smoking cessation efforts are well-established in public health, their integration into acute care settings is often limited. This research advocates for bridging that gap, suggesting that managing nicotine dependence could be a pragmatic and effective avenue to reduce ICU delirium burden, beyond traditional delirium prevention measures.
Future research endeavors should aim to elucidate the biological pathways linking nicotine dependence and delirium, possibly exploring biomarkers of neuroinflammation, cholinergic dysfunction, and withdrawal kinetics in ICU patients. Randomized controlled trials investigating the efficacy and safety of NRT or alternative interventions in nicotine-dependent ICU populations would further refine clinical guidelines.
This study contributes a substantive piece to the intricate puzzle of delirium pathophysiology, highlighting the intersection of addiction medicine and critical care. As ICUs grapple with the multifactorial nature of delirium, recognizing and addressing nicotine dependence emerges as a promising strategy to enhance neurological outcomes and reduce the morbidity associated with critical illness.
In sum, the research underscores nicotine dependence as a distinct and actionable risk factor for delirium in intensive care settings, advocating for enhanced screening, prevention, and therapeutic focus. Integrating these insights into ICU protocols has the potential to transform patient management and reduce the often devastating consequences of delirium in vulnerable populations.
Subject of Research: Relationship between nicotine dependence and the incidence of delirium in intensive care unit patients.
Article Title: Association between nicotine-dependent patients and delirium in intensive care units: a retrospective cohort study using a large clinical database.
Article References: Yang, M., Hu, Z., Huang, Y. et al. Association between nicotine-dependent patients and delirium in intensive care units: a retrospective cohort study using a large clinical database. BMC Psychiatry 25, 1068 (2025). https://doi.org/10.1186/s12888-025-07507-7
Image Credits: AI Generated
DOI: 07 November 2025
Keywords: Nicotine dependence, ICU delirium, critical care, retrospective cohort study, MIMIC-IV database, propensity score matching, neurocognitive disorders, nicotine replacement therapy, neuroinflammation, cholinergic dysfunction
