This retrospective cohort study involved patients aged 70 years or older diagnosed with acute abdominal conditions in the ED of Tosei General Hospital who received intravenous acetaminophen between October 2015 and December 2022.

Data were retrospectively collected from electronic medical records. In this study, delirium was defined as cases in which medical staff recorded a diagnosis of delirium in the electronic medical records. Experienced medical staff assessed delirium based on observed changes in mental status, attention deficits, hallucinations, or illusions. The evaluation period for delirium was set within 7 days of hospital admission. Since delirium commonly develops within the first few days of hospitalization and the average length of stay at Tosei General Hospital is approximately 10 days, we established this evaluation period while considering the potential influence of other factors on delirium onset. The items selected for analysis were based on risk factors for delirium reported in previous studies, focusing on information that can be promptly obtained in the ED to facilitate clinical decision-making. In the ED, patient information is often uncertain, requiring rapid decision-making with limited data. Consequently, data derived from initial assessments in the ED are considered more critical than detailed information obtained after admission. This study investigated the following items that can be assessed early in the ED: age, sex, living situation [11], history of neurodegenerative diseases/dementia sensory impairments (vision/hearing) [12], history of delirium [11, 12], use of drugs associated with the risk of delirium [11, 12], use of six or more medications [11], serum bilirubin [11, 12], albumin [11, 12], blood urea nitrogen (BUN) [11, 12], and creatinine [11, 12] The dosage of acetaminophen was also investigated separately from the above risk factors. As per the guidelines, intravenous administration of 1,000 mg of acetaminophen is recommended for patients with acute abdomen, which is considered a high dose. In this study, we categorized patients into two: the high-dose group (≥ 1000 mg per infusion) and the low-dose group (< 1000 mg per infusion).

Laboratory data were classified according to the blood test reference values established by Tosei General Hospital. Specifically, serum bilirubin was categorized as ≥ 2.0 mg/dL, albumin as ≤ 3.5 g/dL, BUN as ≥ 20 mg/dL, and creatinine as ≥ 2.0 mg/dL. Patients were then divided into two groups based on these cutoff values.

Univariate analysis was first conducted using Fisher's exact test to assess the relationship between post-admission delirium onset and various patient characteristics. The variables included sex, acetaminophen intravenous dose (≥ 1,000 mg/administration vs. < 1,000 mg/administration), presence of neurodegenerative diseases/dementia, history of delirium, sensory impairments (vision/hearing), and serum albumin level (≤ 3.5 g/dL vs. > 3.5 g/dL). Variables with a p-value of < 0.25 in the univariate analysis were selected for multivariate analysis. A multivariate logistic regression analysis was then performed with delirium onset as the dependent variable and the selected factors as independent variables to adjust for confounding factors. The impact of high-dose acetaminophen on the onset of delirium was evaluated using the multivariate logistic regression model. A p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows version 28.0 (IBM Corp., Armonk, NY, USA).

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Tosei General Hospital (Approval No.: 1180) and the Ethics Committee of Nagoya City University (Approval No.: 60–24-0024).