Acetaminophen Linked to Lower Risk of ICU Delirium in Critically ill Patients: Study Shows

USA: A new retrospective cohort study published in the Annals of the American Thoracic Society suggests that acetaminophen may play a significant role in preventing delirium among critically ill patients in the Intensive Care Unit (ICU).

The research, led by Dr. Somnath Bose from the Department of Anesthesia, Critical Care, and Pain Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, highlights the potential of this widely used analgesic to improve outcomes in the ICU beyond its traditional role in pain management.
Delirium is a common and serious complication in ICU patients, associated with increased morbidity, longer hospital stays, and higher mortality. Pain and systemic inflammation are recognized contributors to delirium, but strategies to prevent it outside of the postoperative setting remain limited. The study aimed to investigate whether acetaminophen administration could reduce the incidence of ICU delirium in a broad critically ill population.
The researchers conducted a retrospective analysis of 17,818 adult patients admitted to any ICU in a tertiary hospital for 48 hours or longer between 2015 and 2024. Patients who received at least 2 grams of acetaminophen per day during their ICU stay were considered exposed to the medication. Delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU), which was performed every 12 hours as part of routine clinical care. Multivariate logistic regression models and fractional polynomial analyses were used to explore the relationship between acetaminophen exposure and delirium incidence.
The study led to the following notable findings:
  • Among the cohort, 5,332 patients (29.9%) received acetaminophen during their ICU stay.
  • 5,438 patients (30.5%) developed delirium during their ICU stay.
  • Acetaminophen use was associated with a significant reduction in delirium incidence, with an adjusted odds ratio of 0.66.
  • The absolute risk difference for delirium with acetaminophen use was -6.0%.
  • A dose-dependent relationship was observed: patients with a higher proportion of ICU stay under the effect of acetaminophen experienced less delirium.
  • The protective effect plateaued at approximately 40% coverage of the ICU stay, indicating that sustained exposure may be important for reducing delirium risk.
“These findings suggest that acetaminophen could serve as a safe, readily available intervention to decrease delirium among critically ill patients,” Dr. Bose wrote. The study emphasizes that these results are hypothesis-generating and highlight the need for prospective randomized controlled trials to confirm the efficacy of acetaminophen for delirium prevention in the ICU.
The study provides compelling evidence that acetaminophen is linked to a clinically meaningful reduction in ICU delirium among unselected critically ill patients. The inverse association between the proportion of time patients were under acetaminophen’s effect and the time they experienced delirium indicates a potential strategy for ICU clinicians to mitigate this common and detrimental complication.
“If confirmed in future trials, acetaminophen could become a simple, low-risk approach to improving outcomes for critically ill patients,” the authors concluded.
Reference:
Bose S, Paschold BS, Shamsi T, Kaiser L, Pensier J, Chen G, Nguyen V, Janga SR, Behera A, Talmor D, Subramaniam B, Schaefer MS. Role of Acetaminophen in Intensive Care Unit Delirium Prevention: A Retrospective Cohort Study. Ann Am Thorac Soc. 2025 Aug 4. doi: 10.1513/AnnalsATS.202506-683OC. Epub ahead of print. PMID: 40758474.

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