Zhen J, Li YL, Xu YF, Guo LJ, Chen W. Study on risk factors and interaction effects of delirium in patients with severe pneumonia in intensive care unit. World J Psychiatry 2026; 16(7): 117992 [DOI: 10.5498/wjp.117992]
Corresponding Author of This Article
Wei Chen, MD, Doctor, Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian, Haidian District, Beijing 100038, China. 18101250829@163.com
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Zhen J, Li YL, Xu YF, Guo LJ, Chen W. Study on risk factors and interaction effects of delirium in patients with severe pneumonia in intensive care unit. World J Psychiatry 2026; 16(7): 117992 [DOI: 10.5498/wjp.117992]
Jie Zhen, Yuan-Long Li, Yi-Fei Xu, Wei Chen, Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Jie Zhen, Yuan-Long Li, Yi-Fei Xu, Wei Chen, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Lin-Jia Guo, Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Author contributions: Zhen J conceived the project and wrote the manuscript; Li YL designed the study and acquired the data; Xu YF analyzed the data; Guo LJ reviewed and edited the manuscript; Chen W designed the study and reviewed the manuscript; all authors contributed to the article and approved the submitted version.
Supported by the 2022 Beijing Major Epidemic Prevention and Control Key Specialized Construction Project, No. ZDYQFZZDZK.
Institutional review board statement: This study was approved by the Ethics Committee of Beijing Shijitan Hospital, Capital Medical University (No. IIT2025-023-001).
Informed consent statement: The retrospective study waived informed consent.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The data used in this study can be obtained from the corresponding author upon reasonable request.
Corresponding author: Wei Chen, MD, Doctor, Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian, Haidian District, Beijing 100038, China. 18101250829@163.com
Received: February 3, 2026 Revised: March 12, 2026 Accepted: March 23, 2026 Published online: July 19, 2026 Processing time: 147 Days and 3.2 Hours
Abstract
BACKGROUND
Delirium is a common and serious complication in the intensive care unit (ICU). Its occurrence not only aggravates the original condition but also prolongs mechanical ventilation and hospitalization, and is closely associated with a poor prognosis. We hypothesized that delirium in patients with severe pneumonia in the ICU is not determined by a single factor but by multiple identifiable clinical risk factors and their interaction effects.
AIM
To explore the risk factors and interaction effects of delirium in patients with severe pneumonia in the ICU.
METHODS
A total of 274 patients with severe pneumonia admitted to Beijing Shijitan Hospital, Capital Medical University, between January 2024 and June 2025 were selected. Depending on whether delirium occurred during the ICU stay, the patients were divided into a delirium group (71 cases) and a non-delirium group (203 cases). The risk factors for postoperative delirium were analyzed using logistic regression analysis. Multi-factor dimensionality reduction was used to analyze the interactions between risk factors.
RESULTS
Significant differences in diabetes (P = 0.003), mechanical ventilation time (191.09 ± 43.75 hours vs 136.74 ± 40.92 hours, P < 0.001), blood lactic acid (5.14 ± 1.55 mmol/L vs 2.91 ± 0.74 mmol/L, P < 0.001), blood calcium (2.23 ± 0.15 mmol/L vs 2.36 ± 0.09 mmol/L, P < 0.001), arterial oxygen saturation (P = 0.001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P < 0.001) were observed between the two groups. Mechanical ventilation time [1.029 (1.015-1.044), P < 0.001], blood lactic acid [5.229 (3.017-9.062), P < 0.001] and APACHE II scores [3.368 (1.227-9.246), P = 0.018] were risk factors for delirium in ICU patients with severe pneumonia (all P < 0.05). A significant interaction was found among diabetes, arterial oxygen saturation, and APACHE II score (P < 0.001). The area under the receiver operating characteristic curve (AUC) of the regression model with an interaction effect was 0.531 (P = 0.431). The AUC of the model without an adjusted interaction effect was 0.958 (P < 0.001).
CONCLUSION
Mechanical ventilation time, blood lactic acid, and APACHE II score are delirium risk factors. The interaction among diabetes, arterial oxygen saturation, and APACHE II score may predict delirium.
Core Tip: The results of this study show that delirium affects 25.91% of intensive care unit patients with severe pneumonia. Prolonged mechanical ventilation, elevated blood lactate levels, and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores are independent risk factors for delirium development. Notably, diabetes, arterial oxygen saturation, and APACHE II score demonstrate significant three-way interaction effects, suggesting that delirium results from complex synergistic pathophysiological processes. Early identification of high-risk patients using these combined indicators may enable targeted preventive interventions, ultimately improving clinical outcomes in this vulnerable population.
Citation: Zhen J, Li YL, Xu YF, Guo LJ, Chen W. Study on risk factors and interaction effects of delirium in patients with severe pneumonia in intensive care unit. World J Psychiatry 2026; 16(7): 117992
The intensive care unit (ICU) is a special place for the intensive monitoring, nursing, and treatment of critically ill patients using modern medical theory[1]. Severe pneumonia is a critical stage of pneumonia in patients with respiratory failure, sepsis, shock, multiple organ failure, and pulmonary infection[2]. Severe pneumonia is the most common respiratory disease in the ICU.
Patients with severe pneumonia in the ICU often experience negative emotions, such as irritability, anxiety, and depression, due to the physical pain caused by the disease, coupled with the patient’s concerns about the condition and fear of prognosis[3,4]. The interference of frequent instrument alarm sounds in the ICU, patients’ tension and fear of the unfamiliar ward environment, equipment, pipelines, and other constraints, limited visits, and lack of information can aggravate patients’ negative emotions and even lead to ICU delirium[5,6].
Delirium is a complication with a high incidence among patients admitted to the ICU. It is a neurocognitive syndrome caused by reversible nerve interruption. It typically manifests as fluctuating mental state changes over a short time, such as attention, cognitive, and consciousness disorders[7,8]. Delirium in patients with severe pneumonia in the ICU not only leads to prolonged mechanical ventilation and hospitalization time but also increases the incidence of complications and mortality, affecting patients’ prognoses and quality of life[9]. However, current research on risk factors and their interactions with delirium in patients with severe pneumonia in the ICU remains scant.
Therefore, the purpose of this study was to analyze the risk factors of delirium in patients with severe pneumonia in the ICU and to explore the effect of their interaction on the occurrence of delirium to provide a theoretical basis for reducing the risk of postoperative delirium in patients.
MATERIALS AND METHODS
Patient characteristics
A total of 274 patients with severe pneumonia admitted to the Beijing Shijitan Hospital, Capital Medical University, from January 2024 to June 2025 were selected for this study, aged 37-58 (47.81 ± 3.45) years, including 134 males and 140 females. The body mass index was 18.99-26.42 (22.06 ± 1.18) kg/m2. The types of pneumonia were as follows: 195 cases of community-acquired pneumonia, 79 of hospital-acquired pneumonia, 94 of previous cerebrovascular disease, 83 of hypertension, 40 of diabetes, 72 of coronary heart disease, and 129 of insomnia.
The following inclusion criteria were used: (1) 18-60 years old; (2) Initial diagnosis of severe pneumonia; (3) In line with the diagnostic criteria for severe community-acquired pneumonia in the “Guidelines for the Diagnosis and Treatment of Adult Community-acquired Pneumonia (2018)” and “Guidelines for the Diagnosis and Treatment of Hospital-acquired Pneumonia and Ventilator-associated Pneumonia in Chinese Adults (2018 Edition)”; and (4) Complete clinical data.
The exclusion criteria were as follows: (1) Patients with fatal diseases, such as cerebrovascular disease, myocardial infarction, and end-stage renal disease; (2) Patients with pulmonary tuberculosis, chronic obstructive pulmonary disease, congenital pulmonary dysplasia, and other lung diseases; (3) Autoimmune diseases and malignant tumors; (4) Lactating and pregnant women; and (5) Patients with mental illness.
This study was approved by the Ethics Committee of Beijing Shijitan Hospital, Capital Medical University (No. IIT2025-023-001). The retrospective nature of the study waived the need for informed consent. The research process is shown in Figure 1.
Diagnostic criteria of delirium and grouping of patients
Delirium was diagnosed according to the third edition of the American Diagnostic and Statistical Manual of Mental Disorders: (1) Acute onset or fluctuating changes in mental state; (2) Difficulty concentrating; (3) Confusion of thinking; and (4) Change in consciousness. Exhibiting (2) and (3) or (1); (2), and (4), or (2); (3), and (4) can be diagnosed as delirium. Based on whether delirium occurred during ICU hospitalization in patients with severe pneumonia, the patients were divided into delirium (71 cases) and non-delirium (203 cases) groups.
Clinical data collection related to delirium
The clinical data of the two groups were collected, including age, gender, body mass index, type of pneumonia, smoking history, drinking history, cerebrovascular disease, hypertension, diabetes, coronary heart disease, insomnia, course of disease, mechanical ventilation time, white blood cell count, platelet count, serum creatinine, blood lactic acid, blood urea nitrogen, hemoglobin, blood calcium, blood sodium, blood potassium, C-reactive protein, arterial oxygen saturation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, sedative use, nutritional risk, and other data.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics version 23.0 (IBM Corp., Armonk, NY, United States) and multi-factor dimensionality reduction (MDR) software version 3.0.2 for interaction analysis. The measurement data were expressed as mean ± SD, and a t-test (for normally distributed data with equal variances) was used for comparison between the groups. The enumeration data were expressed as a percentage (%), and the rate was compared using the χ2 test. A logistic regression model was used to analyze independent risk factors for delirium. MDR was used to analyze the interaction between risk factors, and the optimal interaction effect model was calculated using the MDR software. A receiver operating characteristic (ROC) curve was used to analyze the efficacy of the regression model in predicting the risk of postoperative delirium; P < 0.05 was considered statistically significant.
RESULTS
Comparison of general data between the two groups
Of the 274 patients, 71 had delirium, and 203 did not. The incidence of delirium in patients with severe pneumonia in the ICU was 25.91% (71/274 patients). Significant differences in diabetes mellitus (P = 0.003), mechanical ventilation time (191.09 ± 43.75 hours vs 136.74 ± 40.92 hours, P < 0.001), blood lactic acid (5.14 ± 1.55 mmol/L vs 2.91 ± 0.74 mmol/L, P < 0.001), blood calcium (2.23 ± 0.15 mmol/L vs 2.36 ± 0.09 mmol/L, P < 0.001), arterial oxygen saturation (P = 0.001), and APACHE II score (P < 0.001) between the two groups were observed, as shown in Table 1.
Table 1 Comparison of general data, mean ± SD/n (%).
Analysis of risk factors affecting postoperative delirium
A logistic regression model was established with the occurrence of delirium as the dependent variable (assignment 1 = delirium group, 0 = non-delirium group). The independent variables were diabetes, mechanical ventilation time, blood lactic acid, blood calcium, arterial oxygen saturation, and APACHE II scores. The assignments are presented in Table 2. Multivariate logistic regression analysis showed that mechanical ventilation time [1.029 (1.015-1.044), P < 0.001], blood lactic acid [5.229 (3.017-9.062), P < 0.001], and APACHE II scores [3.368 (1.227-9.246), P = 0.018] were risk factors for delirium in ICU patients with severe pneumonia, as shown in Table 3.
Six factors (diabetes, mechanical ventilation time, blood lactic acid, blood calcium, arterial oxygen saturation, and APACHE II score) with P < 0.05 in the univariate analysis were further constructed using the MDR software. Consequently, three statistically significant interaction models were developed, as shown in Table 4. In the first-order interaction model, the APACHE II score had a significant effect on delirium. In the second-order interaction model, a significant interaction was found between diabetes and the APACHE II score on the occurrence of delirium. The third-order interaction model included three factors: Diabetes, arterial oxygen saturation, and the APACHE II score. It had the highest cross-validation consistency rate (10/10) and average test accuracy (68.38%), and was the best interaction model for predicting delirium.
Table 4 Interaction effect analysis of risk factors for delirium in intensive care unit patients with severe pneumonia.
The effect of interaction on postoperative delirium
A statistically significant interaction effect was included as a new variable in the multivariate logistic regression model; the results are presented in Table 5. The interaction model showed that APACHE II score and diabetes × APACHE II score had no significant effect on the occurrence of delirium (P = 0.531). Diabetes × arterial oxygen saturation × APACHE II score significantly affected the occurrence of delirium (P = 0.007).
Table 5 Multivariate logistic regression analysis of risk factors and interaction effects of delirium in patients with severe pneumonia in the intensive care unit.
ROC analysis was performed on the regression model adjusted for the interaction effect; the results are shown in Figure 2. The area under the curve (AUC) of the regression model with an interaction effect was 0.531 (P = 0.431). The AUC of the model without an adjusted interaction effect was 0.958 (P < 0.001).
Figure 2 The receiver operating characteristic curve of delirium in intensive care unit patients with severe pneumonia was predicted using a regression model.
AUC: Area under the curve.
DISCUSSION
Delirium is a common complication in patients with severe pneumonia in the ICU. It not only aggravates the original condition and prolongs the length of hospital stay but also directly affects patients’ final prognoses[10,11]. However, current research on risk factors and their interactions with delirium in patients with severe pneumonia in the ICU remains relatively limited. In this study, the clinical data of patients with severe pneumonia in the ICU were analyzed to identify the risk factors for delirium and explore the interaction effects to provide a scientific basis for early clinical identification, prevention, and intervention.
The number of delirium cases (n = 71) is relatively modest in the present study. This sample size is consistent with many clinical observational studies on delirium. Our logistic regression models included only a limited number of clinically relevant variables, thus avoiding overfitting and maintaining statistical stability. Our analysis identifies elevated APACHE II scores, prolonged mechanical ventilation, and increased blood lactic acid levels as significant predictors of delirium in ICU patients with severe pneumonia. The APACHE II score is a classic tool used to evaluate disease severity in ICU patients[12,13]. Patients with higher scores (≥ 15) typically present with profound physiological dysregulation and require complex interventions, creating a pathophysiological milieu conducive to delirium[14,15]. This aligns with existing literature confirming a positive correlation between disease severity and delirium risk[16,17]. Similarly, the duration of mechanical ventilation acts as a proxy for the severity and persistence of the critical illness[18,19]. Prolonged ventilation not only indicates a slower recovery and sustained systemic inflammation[20,21], but also subjects patients to significant psychophysical stressors, including discomfort, communication barriers, and anxiety, all of which are known contributors to delirium[22-24]. Our findings are consistent with studies showing a sharp increase in delirium incidence after 72 hours of ventilation[25]. Furthermore, elevated blood lactate, a marker of tissue hypoperfusion and anaerobic metabolism[26,27], emerged as a powerful predictor. In severe pneumonia, impaired gas exchange can lead to systemic hypoxia, and the resulting increase in lactate likely reflects cerebral tissue distress, potentially precipitating brain dysfunction and delirium[28-30]. Therefore, in clinical practice, the frequency of visits should be increased, the state of consciousness should be closely monitored, and professional scales such as the confusion assessment method for the ICU should be used for dynamic evaluation to achieve early warning and intervention for delirium[31]. An interaction analysis of risk factors was conducted, and interactions among three factors, namely, diabetes, arterial oxygen saturation, and APACHE II score, were found. The interactions among these three factors may be related to the risk of delirium. Although the subsequent ROC verification analysis was not statistically significant, it can be inferred that delirium in ICU patients with severe pneumonia results from an interaction of multiple factors.
In this study, we restricted the age range to 18-60 years to minimize confounding from age-related comorbidities and developmental factors. However, this limits the generalizability of our findings to pediatric and elderly populations, who may exhibit different treatment responses due to variations in drug metabolism and immune function. As this was a single-center study, the sample size was small; thus, selection bias may have been present. Despite the limited sample size, our study still provides valuable realworld evidence on risk factors and clinical correlates of delirium. Delirium assessment relied on screening by nursing staff, which may miss hypoactive delirium compared to continuous monitoring. Future research should conduct multi-regional and multi-center studies to expand the sample size and further analyze the differences between the risk factors.
CONCLUSION
In summary, mechanical ventilation time, blood lactic acid level, and APACHE II score are risk factors for delirium in patients with severe pneumonia in the ICU. The preliminary exploration of this study found that an interaction effect may exist between diabetes history, arterial oxygen saturation, and APACHE II score, suggesting that delirium in patients with severe pneumonia in the ICU is the complex result of multiple factors rather than a simple superposition of a single risk.
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