Statin Use is Associated with Reduced Delirium and Improved Short- Term Outcomes in Critically Ill Patients with Chronic Kidney Disease

Statin Use is Associated with Reduced Delirium and Improved Short- Term Outcomes in Critically Ill Patients with Chronic Kidney Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Statin Use is Associated with Reduced Delirium and Improved Short- Term Outcomes in Critically Ill Patients with Chronic Kidney Disease Yuanhao Chen, Tongtong Li, Zhikui Huo, Yuzhen Zhong, Xiu Wen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7482282/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Nov, 2025 Read the published version in European Journal of Medical Research → Version 1 posted 14 You are reading this latest preprint version Abstract Background: Delirium is a common and serious neurocognitive complication in critically ill patients, particularly those with chronic kidney disease (CKD), who are predisposed due to systemic inflammation, metabolic dysregulation, and polypharmacy. Statins, widely used for their cardiovascular benefits, also possess anti-inflammatory and neuroprotective properties that may influence delirium risk. However, their impact on delirium incidence and short-term prognosis in CKD patients remains unclear. Methods: We conducted a retrospective cohort study using the MIMIC-IV database, identifying 3218 adult patients with CKD admitted to the intensive care units (ICU). Patients were stratified based on statin exposure during the three days before and after ICU admission. The primary outcome was the incidence of delirium, which was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Secondary outcomes included all-cause mortality at 30 days and 90 days. Propensity score matching (PSM) was employed to balance baseline characteristics, and multivariable logistic and Cox regression models were utilized to estimate associations. Results: Before matching, statin use was associated with significantly lower delirium incidence (25.0% vs. 34.4%, p < 0.001) and lower 30-day mortality (20.4% vs. 28.7%, p < 0.001). After 1:1 PSM (n = 2132), these associations remained significant: statin use correlated with reduced odds of delirium (adjusted OR 0.60, 95% CI: 0.49–0.74, p < 0.001), and lower 30-day (HR 0.82, 95% CI: 0.69–0.97, p = 0.019) and 90-day mortality (HR 0.80, 95% CI: 0.69–0.93, p = 0.003). Subgroup analyses showed consistent findings across CKD stages and comorbidity profiles, with notable interaction observed in benzodiazepine users (interaction for p = 0.009). Conclusion: Among critically ill patients with CKD, statin use is independently associated with a lower risk of delirium and improved short-term survival. These findings support the potential neuroprotective role of statins in this high-risk population and warrant further investigation through prospective studies and randomized controlled trials. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction CKD is a clinical syndrome characterized by a progressive decline in renal function. Diagnosis is based on criteria that include persistent (greater than three months) structural or functional renal abnormalities, sustained proteinuria or hematuria detected through urinalysis, and biochemical alterations such as metabolic imbalances of uremic toxins. CKD has become a major global health challenge, affecting approximately 850 million people worldwide ( 1 ). Among its numerous systemic impacts, CKD has been increasingly recognized as a risk factor for cognitive dysfunction and neuropsychiatric complications, including delirium. The susceptibility may stem from the accumulation of neurotoxic uremic solutes and impaired clearance of medications such as sedatives ( 2 , 3 ) and analgesics ( 4 ), especially during critical illness. Delirium is a transient but severe neurocognitive disorder marked by an acute onset and fluctuating disturbance in attention, awareness, and cognition. It is commonly precipitated by acute illness, medications, or physiological stressors, and frequently occurs in hospitalized patients, particularly those in ICU. Incidence rates in ICU populations can exceed 60%, with even higher rates in high-risk groups such as the elderly and those with multiple comorbidities ( 2 ). Importantly, delirium is independently associated with a variety of adverse outcomes, including prolonged mechanical ventilation, extended ICU and hospital stays, long-term cognitive impairment, and elevated short- and long-term mortality rates ( 3 , 5 ). Despite its clinical significance, delirium is often underdiagnosed and lacks effective pharmacologic preventive strategies. Patients with CKD are especially vulnerable to delirium, owing to factors such as metabolic dysregulation, anemia, polypharmacy, and systemic inflammation. The risk is further amplified in the ICU, where CKD patients frequently require complex interventions, are more prone to hemodynamic instability, and often experience acute-on-chronic kidney injury ( 6 ). Observational studies have found that CKD is an independent risk factor for delirium in critically ill patients, with worse short-term and long-term outcomes ( 7 ). Nevertheless, few studies have evaluated targeted interventions for delirium in this patient group, and the role of commonly used medications, such as statins, remains unclear. Statins, or HMG-CoA reductase inhibitors, are widely prescribed for their lipid-lowering and cardiovascular protective effects. Beyond their primary indication, statins exhibit pleiotropic properties, including anti-inflammatory, immunomodulatory, and antioxidant effects, as well as enhancement of endothelial function ( 8 ). These effects are particularly relevant in the context of delirium, which is thought to arise from systemic inflammation and neuroinflammation. Simvastatin has been shown to reduce microglial activation, suppress proinflammatory cytokines, and improve cognitive function in lipopolysaccharide-induced neuroinflammation in mice ( 9 ). Similarly, atorvastatin has demonstrated protective effects on the blood–brain barrier and neuronal apoptosis in models of surgically induced encephalopathy ( 10 ). Despite this theoretical benefit, the clinical literature on statins and delirium remains inconclusive. Some observational studies and meta-analyses suggest a reduced risk of delirium with preadmission statin use, particularly in surgical and ICU populations ( 11 , 12 ). Conversely, other studies report either no association or a potential increase in delirium risk, possibly due to statin-induced sleep disturbances, drug interactions, or effects on neuronal cholesterol metabolism ( 13 , 14 ). To date, no research has specifically examined the impact of statins on delirium incidence among patients with CKD, despite this population's elevated baseline risk and frequent statin use. To address this knowledge gap, the present study utilizes the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to investigate the association between statin use and delirium incidence among critically ill patients with CKD. Methods Data source This retrospective study utilized data from the MIMIC-IV database (version 3.1), a publicly available single-center intensive care medicine database. The database encompasses comprehensive clinical data of patients admitted to the ICUs at Beth Israel Deaconess Medical Center in Boston, Massachusetts, spanning the years 2008 to 2019. This dataset includes detailed information on demographics, vital signs, laboratory tests, and treatment protocols. The MIMIC-IV dataset was de-identified and approved by the Institutional Review Board (IRB) of the Massachusetts Institute of Technology (MIT), and it did not require informed consent. Given that no additional data collection was performed, no further ethical declaration was required for this study. The research team was authorized to use the database by completing mandatory training programs and passing the corresponding examinations (certificate number: 59948527). Study population MIMIC-IV (v3.1) documented 65366 cases of first-time ICU admissions. Patients diagnosed with CKD were identified using International Classification of Diseases, 9th Revision (ICD-9) or 10th Revision (ICD-10) codes. Exclusion criteria included: ( 2 ) ICU stay < 72 hours; ( 3 ) age < 18 years; ( 3 ) diagnosis without CKD and ( 4 ) absence of delirium assessments during ICU admission. Finally, 3218 eligible CKD patients were divided into the statin group (n = 1778) and non-statin group (n = 1440). Data extraction and processing Raw data for CKD patients were extracted from MIMIC-IV (v3.1) using Navicat Premium (version 17.0), including demographics, vital signs, comorbidities, laboratory results, treatment interventions, disease severity scores. Vital signs included heart rate (HR), mean blood pressure (MBP), respiratory rate (RR). Comorbidities collected congestive heart failure (CHF), coronary artery disease (CAD), Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease (CVD), diabetes, cancer and CKD stage. Laboratory parameters included hematocrit (HCT), hemoglobin (HGB), platelets (PLT), white blood cells (WBC), anion gap, bicarbonate, chloride, potassium, sodium, blood urea nitrogen (BUN), calcium, creatinine, glucose. Vital signs and laboratory values were averaged over the first day of ICU admission. Treatment interventions included use of benzodiazepines (BZs), propofol, vasopressor (dopamine, norepinephrine, phenylephrine, vasopressin), cortisone, renal replacement treatment (RRT), mechanical ventilation (VEN), within 3 days of ICU admission. Disease severity was assess using the, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score II (SAPSII), Oxford acute severity of illness score (OASIS) and Sequential Organ Failure Assessment (SOFA) score. Variables with > 6% missing data were excluded (proportion of missing in each variables shown in Table S1), and remaining missing values were imputed using the ‘mice’ package for multiple imputation ( 15 ). Exposure and outcomes Patients were categorized into the statin group (statin use within 3 days of ICU admission) and non-statin group. The primary outcome was delirium incidence during ICU stay, while the secondary outcome was 30-day mortality. Delirium was diagnosed using the CAM-ICU ( 16 ), which requires meeting criteria 1 and 2 plus either 3 or 4: ( 1 ) acute mental status change or fluctuating course; ( 2 ) inattention; ( 3 ) disorganized thinking; ( 4 ) altered consciousness level. CAM-ICU assessments in MIMIC-IV were performed by trained healthcare professionals followed by above standards, with evaluations performed at least twice daily. Statistical analysis Patient characteristics were described overall and by group (statin vs. non-statin). Continuous variables were reported as mean ± SD or median (Interquartile range) based on normality and non-normality, with group comparisons using two independent samples student’s test or Mann-Whitney U tests. Categorical variables were presented as percentages and compared via chi-square tests. PSM with a 1:1 ratio and caliper width of 0.1 was used to balance baseline characteristics. Standardized mean differences (SMDs) were used to evaluate the balance between groups, with an SMD of less than 0.1 generally indicating adequate covariate balance. Logistic regression was used to estimate statin exposure and delirium. The Kaplan-Meier (KM) curves depicted the temporal survival trends over 30 and 90 days in the statin and non-statin groups before and after PSM and log-rank tests was used to compared. Subgroup analyses stratified by age, gender, CHF, CAD, COPD, CVD, diabetes, cancer CKD stage, use of BZs and propofol, CCI, SAPSII, OASIS and SOFA. All analyses were conducted using R software (version 4.4.0; http://www.R-project.org ) and Z Statistical Platform ( https://www.medsta.cn/software ). A two-tailed test was used, and p-value < 0.05 was considered statistically significant. Results Baseline characteristic After applying exclusion criteria, a total of 3218 first-time ICU-admitted CKD patients were included in the study, with 1440 (44.7%) in the non-statin group and 2263 (55.3%) in the statin group (Fig. 1 ). Table 1 compares the baseline characteristics of ICU patients with CKD who received statin therapy versus those who did not, both before and after PSM. Table 1 Baseline characteristic. Before PSM After PSM Total (n = 3218) Nonstatin (n = 1440) Statin (n = 1778) P SMD Total (n = 2132) Nonstatin (n = 1066) Statin (n = 1066) P SMD Age (year) 74.8 (65.5, 82.8) 73.0 (61.8, 82.1) 76.1 (68.2, 83.2) < 0.001 0.369 75.7 (66.9, 83.1) 75.4 (66.5, 83.6) 75.8 (67.4, 82.8) 0.813 0.010 Gender (male %) 2040 (63.4) 856 (59.4) 1184 (66.6) < 0.001 0.152 1333 (62.5) 659 (61.8) 674 (63.2) 0.502 0.029 Vital sign HR (beats/min) 83.8 ± 16.0 86.0 ± 17.2 82.0 ± 14.7 < 0.001 0.276 83.5 ± 16.0 83.8 ± 16.7 83.3 ± 15.3 0.538 0.028 RR (beats/min) 19.6 ± 3.8 20.0 ± 4.0 19.3 ± 3.5 < 0.001 0.208 19.6 ± 3.8 19.6 ± 3.8 19.6 ± 3.7 0.907 0.005 MBP (mmHg) 75.1 (69.6, 82.7) 75.5 (69.8, 83.2) 74.8 (69.4, 82.4) 0.092 0.043 75.5 (69.8, 83.3) 75.7 (69.9, 83.6) 75.3 (69.6, 82.8) 0.358 0.013 Comorbidity, n (%) CHF 1769 (55.0) 690 (47.9) 1079 (60.7) < 0.001 0.261 1171 (54.9) 579 (54.3) 592 (55.5) 0.571 0.025 CAD 1364 (42.4) 367 (25.5) 997 (56.1) < 0.001 0.616 765 (35.9) 364 (34.2) 401 (37.6) 0.095 0.072 COPD 90 (2.8) 37 (2.6) 53 (3.0) 0.482 0.024 68 (3.2) 33 (3.1) 35 (3.3) 0.805 0.011 CVD 673 (20.9) 279 (19.4) 394 (22.2) 0.053 0.067 476 (22.3) 223 (20.9) 253 (23.7) 0.119 0.066 Diabetes 1636 (50.8) 620 (43.1) 1016 (57.1) < 0.001 0.285 1055 (49.5) 519 (48.7) 536 (50.3) 0.461 0.032 Cancer 415 (13.0) 247 (17.2) 168 (9.5) < 0.001 0.263 285 (13.4) 152 (14.3) 133 (12.5) 0.227 0.054 CKD stage 596 (18.5) 291 (20.2) 305 (17.2) 0.027 0.081 379 (17.8) 191 (17.9) 188 (17.6) 0.865 0.007 Lab events HCT (10 9 /L) 31.1 ± 6.3 31.0 ± 6.6 31.2 ± 5.9 0.275 0.041 31.5 ± 6.3 31.5 ± 6.5 31.5 ± 6.1 0.900 0.006 HGB (g/dL) 10.0 ± 2.1 10.0 ± 2.2 10.1 ± 2.0 0.263 0.042 10.1 ± 2.1 10.1 ± 2.1 10.2 ± 2.0 0.872 0.007 PLT (10 9 /L) 175.0 (128.0, 234.5) 170.0 (118.0, 235.6) 178.0 (135.0, 233.4) < 0.001 0.087 179.5 (133.5, 238.0) 176.5 (128.5, 236.9) 182.0 (137.6, 240.0) 0.045 0.097 WBC (10 9 /L) 11.6 (8.5, 15.3) 11.8 (8.2, 15.9) 11.5 (8.7, 15.0) 0.597 0.161 11.5 (8.3, 15.2) 11.6 (8.1, 15.4) 11.5 (8.5, 15.1) 0.593 0.020 Aniongap (mmol/L) 15.5 (13.0, 18.5) 16.0 (13.5, 19.0) 15.0 (12.5, 18.0) < 0.001 0.277 15.5 (13.0, 18.5) 15.5 (13.0, 18.5) 15.0 (13.0, 18.5) 0.466 0.022 Bicarbonate (mmol/L) 21.7 ± 4.4 21.3 ± 4.8 22.0 ± 4.1 < 0.001 0.183 21.9 ± 4.5 21.9 ± 4.7 21.9 ± 4.2 0.746 0.015 Chloride (mmol/L) 102.4 ± 7.0 102.0 ± 7.5 102.7 ± 6.4 0.006 0.107 102.5 ± 7.0 102.5 ± 7.3 102.5 ± 6.7 0.961 0.002 Potassium (mmol/L) 4.5 ± 0.7 4.5 ± 0.7 4.5 ± 0.6 0.504 0.025 4.5 ± 0.7 4.5 ± 0.7 4.5 ± 0.7 0.359 0.041 Sodium (mmol/L) 138.0 (135.0, 141.0) 138.0 (134.5, 141.0) 138.0 (135.5, 140.5) 0.276 0.024 138.0 (135.4, 141.0) 138.0 (135.0, 141.5) 138.0 (135.5, 140.5) 0.239 0.063 BUN (mmol/L) 36.0 (24.1, 56.5) 38.5 (26.0, 62.0) 34.0 (23.0, 52.4) < 0.001 0.230 36.5 (24.0, 57.0) 37.5 (24.0, 58.0) 35.5 (23.0, 56.0) 0.246 0.024 Calcium (mmol/L) 8.5 (8.0, 8.9) 8.4 (7.94, 8.9) 8.5 (8.1, 8.9) 0.006 0.085 8.5 (8.0, 9.0) 8.5 (8.0, 9.0) 8.5 (8.1, 9.0) 0.137 0.036 Creatinine (mg/dL) 1.9 (1.4, 3.3) 2.1 (1.4, 3.6) 1.8 (1.4, 3.0) < 0.001 0.157 1.9 (1.4, 3.3) 1.9 (1.4, 3.3) 1.9 (1.4, 3.2) 0.432 0.032 Glucose (mg/dL) 136.5 (112.0, 178.5) 136.5 (112.0, 179.0) 136.3 (112.0, 177.5) 0.999 0.013 137.0 (112.0, 179.5) 138.0 (112.5, 178.0) 136.0 (112.0, 181.4) 0.952 0.017 Treatment, n (%) BZs 1782 (55.4) 889 (61.7) 893 (50.2) < 0.001 0.230 1186 (55.6) 596 (55.9) 590 (55.4) 0.794 0.011 Propofol 1876 (58.3) 810 (56.3) 1066 (60.0) 0.034 0.076 1188 (55.7) 577 (54.1) 611 (57.3) 0.138 0.064 Vasopressor 775 (24.1) 383 (26.6) 392 (22.1) 0.003 0.110 509 (23.9) 248 (23.3) 261 (24.5) 0.509 0.028 Cortisone 191 (6.0) 101 (7.0) 90 (5.1) 0.020 0.089 137 (6.4) 75 (7.0) 62 (5.8) 0.251 0.052 RRT 804 (25.0) 407 (28.3) 397 (22.3) < 0.001 0.143 500 (23.5) 252 (23.6) 248 (23.3) 0.838 0.009 VEN 2012 (62.5) 894 (62.1) 1118 (62.9) 0.643 0.016 1303 (61.1) 642 (60.2) 661 (62.0) 0.399 0.037 Scores CCI 8.0 (7.0, 10.0) 8.0 (6.0, 9.0) 8.0 (7.0, 10.0) < 0.001 0.190 8.0 (7.0, 10.0) 8.0 (7.0, 10.0) 8.0 (7.0, 10.0) 0.528 0.031 SAPSII 44.0 (36.0, 53.0) 45.0 (37.0, 56.0) 42.0 (36.0, 52.0) < 0.001 0.165 43.5 (36.0, 53.0) 44.0 (36.0, 54.0) 43.0 (36.0, 53.0) 0.583 0.001 OASIS 34.0 (29.0, 40.0) 35.0 (29.0, 42.0) 34.0 (28.0, 39.0) < 0.001 0.178 34.0 (29.0, 40.0) 34.5 (29.0, 41.0) 34.0 (29.0, 40.0) 0.431 0.027 SOFA 6.0 (4.0, 9.0) 7.0 (4.0, 10.0) 6.0 (4.0, 9.0) < 0.001 0.294 6.0 (4.0, 9.0) 6.0 (4.0, 9.0) 6.0 (4.0, 9.0) 0.734 0.011 Events Delirium, n(%) 938 (29.2) 496 (34.4) 442 (25.0) < 0.001 - 641 (30.0) 366 (34.3) 275 (25.8) < 0.001 - 30-day Mortality, n( %) 776 (24.1) 413 (28.7) 363 (20.4) < 0.001 - 534 (25.1) 293 (27.5) 241 (22.6) 0.009 - 90-day Mortality, n(%) 1066 (33.1) 567 (39.4) 499 (28.1) < 0.001 - 729 (34.2) 399 (37.4) 330 (31.0) 0.002 - Data are presented as mean ± sd, medians (interquartile ranges), or numbers (percentages). HR, heart rate; MBP, mean blood pressure; RR, respiratory rate; CHF, congestive heart failure; CAD: coronary artery disease; CVD, cerebrovascular disease; COPD: chronic obstructive pulmonary disease; HCT, hematocrit; HGB, hemoglobin; PLT, platelets; WBC, white blood cell count; BUN, blood urea nitrogen; BZs, benzodiazepines; RRT, renal replacement treatment; VEN, mechanical ventilation; CCI, Charlson Comorbidity index; SAPS II, Simplified Acute Physiology Score Index; OASIS, Oxford acute severity of illness score, SOFA, Sequential Organ Failure Assessment. Before PSM, significant differences were observed between the statin and non-statin groups. The statin group was older than non-stain (76.1 years vs. 73.0 years, P < 0.001), and there was a higher proportion of males in the statin group (66.6% vs. 59.4%, P < 0.001). Additionally, patients in the statin group had a higher prevalence of comorbidities, including CHF, CAD, and COPD. Statin group had less use of BZs (50.2% vs. 61.7%, P < 0.001) and more commonly used of propofol (60.0% vs. 56.3%, P = 0.034). Patients in the statin group had a lower incidence of delirium (25.0% vs. 34.4%, P < 0.001) than non-statin group, as well as lower 30-day mortality(20.4% vs. 28.7%, P < 0.001) and 90-day mortality rates (28.1% vs. 39.4%, P < 0.001). After PSM for non-outcome confounding factors, there were 1066 patients in each group. The standardized mean differences (SMD) for all variables were below 0.1, indicating successful matching and balance of covariates between two groups. Age and gender differences were no longer significant (P = 0.813 and P = 0.502, respectively), and comorbidities such as CHF, CAD, and COPD, which were more prevalent in the statin group before matching, showed no significant difference after matching (P = 0.571, P = 0.095, P = 0.805, respectively). Patients using BZs and propofol show no difference statistically between groups with and without statin. However, after PSM, consistent with the results before PSM, patients in the statin-exposure patients remains showing a lower 30-day (22.6% vs. 27.5%, P = 0.009) and 90-day mortality rates (31.0% vs. 37.4%, P = 0.002). Association between statin and delirium in CKD patients Table 2 presents the relationship between statin use and delirium incidence in ICU-admitted CKD patients, analyzed using logistic regression models both before and after PSM. Before PSM, the crude model showed a significantly negative association between statin use and delirium (OR: 0.63, 95% CI: 0.54–0.73, P < 0.001). This negative association remained robust after adjusting for age and gender (Model 1: OR: 0.62, 95% CI: 0.53–0.73, P < 0.001), and further adjustments for comorbidity (Model 2: OR: 0.54, 95% CI: 0.46–0.64, P < 0.001), vital sign, comorbidity, lab events, treatment, and disease severity scores (Model 3: OR: 0.63, 95% CI: 0.52–0.76, P < 0.001). After PSM, statin use continued to show a significant negative correlation with delirium in all models, with the adjusted odds ratio in Model 3 being 0.60 (95% CI: 0.49–0.74, P < 0.001). These results consistently indicate that statin exposure is associated with a reduced risk of delirium in ICU patients, regardless of PSM or adjustment for various confounders. Table 2 Relationship between statin and the incidence of delirium in different models before and after propensity score matching. Non-statin vs.Statin Before PSM After PSM OR, 95% CI P OR, 95% CI P Crude model 0.63 (0.54–0.73) < 0.001 0.66 (0.55–0.80) < 0.001 Model 1 0.62 (0.53–0.73) < 0.001 0.67 (0.55–0.80) < 0.001 Model 2 0.54 (0.46–0.64) < 0.001 0.66 (0.55–0.80) < 0.001 Model 3 0.63 (0.52–0.76) < 0.001 0.60 (0.49–0.74) < 0.001 Model 1: adjusted for age and gender; Model 2: adjusted for age, gender and comorbidity; Model 3: adjusted for age, gender, vital sign, comorbidity, lab events, treatment and disease severity scores. According to the previous report, the properties of statins may influence the efficacy of the drug in preventing the occurrence of delirium. As shown in Table 3 , we further stratified the analysis based on the physicochemical properties of statins to examine their respective associations with the risk of delirium, using non-statin users as the reference group. Before PSM, both hydrophilic and lipophilic statins were associated with a significantly reduced risk of delirium. Specifically, hydrophilic statins showed an odds ratio (OR) of 0.69 (95% CI: 0.53–0.91, P = 0.008), while lipophilic statins demonstrated an even stronger association (OR: 0.62, 95% CI: 0.52–0.72, P < 0.001). After PSM, the protective effect of lipophilic statins remained statistically significant, with an OR of 0.55 (95% CI: 0.44–0.69, P < 0.001). In contrast, the association between hydrophilic statin use and delirium was attenuated and no longer reached statistical significance (OR: 0.83, 95% CI: 0.58–1.20, P = 0.271). Table 3 Analysis of the relationship between statin properties and delirium. Before PSM After PSM OR, 95% CI P OR, 95% CI P Non-statin vs. Hydrophilic statins 0.69 (0.53–0.91) 0.008 0.83 (0.58–1.20) 0.271 Non-statin vs. Lipophilic statins 0.62 (0.52–0.72) < 0.001 0.55 (0.44–0.69) < 0.001 Table 4 Univariate and multivariable cox regression analysis before and after propensity score matching. Non-statin vs.Statin Before PSM After PSM HR, 95% CI P HR, 95% CI P 30-day mortality Univariate Cox logistic analysis 0.69 (0.60–0.80) < 0.001 0.82 (0.69–0.97) 0.019 Multivariate Cox logistic analysis 1 0.85 (0.73–0.99) 0.035 0.84 (0.71–1.00) 0.053 90-day mortality Univariate Cox logistic analysis 0.67 (0.59–0.76) < 0.001 0.80 (0.69–0.93) 0.003 Multivariate Cox logistic analysis 1 0.80 (0.70–0.91) < 0.001 0.81 (0.70–0.94) 0.006 1 : adjusted for age, gender, comorbidity, vital sign, lab events, treatment and disease severity scores. The association of Statin Use with prognosis in CKD Patients Before PSM, statin use was significantly associated with lower mortality rates. In the univariate analysis, the HR for 30-day mortality was 0.69 (95% CI: 0.60–0.80, P < 0.001), and for 90-day mortality was 0.67 (95% CI: 0.59–0.76, P < 0.001). These associations remain significant after adjusting for age, gender, comorbidity, vital sign, lab events, treatment and disease severity scores. For 30-day mortality, the HR was 0.85 (95% CI: 0.73–0.99, P = 0.035), and for 90-day mortality, the HR was 0.80 (95% CI: 0.70–0.91, P < 0.001). After PSM, the association between statin use and mortality remained significant, although the strength of the association was somewhat attenuated. For 30-day mortality, the HR was 0.82 (95% CI: 0.69–0.97, P = 0.019), and for 90-day mortality, the HR was 0.80 (95% CI: 0.69–0.93, P = 0.003). These associations show different in 30-day and 90-day mortality after adjusting for all the same factors. For 30-day mortality, the HR was 0.84 (95% CI: 0.71–1.00, P = 0.053), although this relationship is not statistically significant, it demonstrates a consistent trend, and for 90-day mortality, the HR was 0.80 (95% CI: 0.70–0.94, P = 0.006). Figure 2 and 3 show Kaplan-Meier survival curves for 30-day and 90-day mortality risk model, respectively in statin and non-statin groups. Both figures clearly indicate that statin use is associated with significantly higher survival rates compared to the non-statin group. KM survival curves for the post-PSM risk model are shown in Additional file 1: Fig. S2 and S3 and remains significant in statin and non-statin group. Subgroup Analysis of Statin Use and Delirium Incidence Figure 4 presents a forest plot of the subgroup analysis examining the effect of statin use on the incidence of delirium across various patient subgroups. Overall, statin use was consistently associated with a lower incidence of delirium compared to the non-statin group.The protective effect of statins against delirium was observed across multiple subgroups, including patients with different comorbidities such as CHF, CAD, COPD, as well as varying severity scores like SAPS II and SOFA.The same trend was observed in subgroups based on the use of specific treatments, such as benzodiazepines or propofol. There is an interaction of statin use and delirium incidence between the BZs users and non-users(p = 0.009). Compared to patients who did not use benzodiazepines, exposure to benzodiazepines may increase risk of delirium associated with statin use. Discussion In this retrospective cohort study involving 3218 patients with CKD admitted to the ICU, we found that statin use was significantly associated with a lower incidence of delirium, as well as reduced 30-day and 90-day mortality. These associations remained consistent after adjusting for confounders and applying 1:1 propensity score matching. To our knowledge, it is the first study to specifically investigate the relationship between statin therapy and delirium among patients with CKD. The relationship between statin therapy and delirium remains controversial. A large retrospective analysis involving over 280000 patients aged 65 and older undergoing elective surgery suggested a higher incidence of postoperative delirium among those using statins ( 17 ). However, this study has several important limitations that warrant cautious interpretation. Despite its large sample size, the findings may be confounded by substantial baseline heterogeneity and unmeasured variables such as frailty, cognitive status, and medication adherence—factors that are known to influence delirium risk but were not adequately controlled. Another retrospective study focusing on patients who underwent coronary artery bypass grafting reported a neutral effect of statin use on delirium ( 18 ). Notably, both studies limited the exposure window to the period between hospital admission and the day prior to surgery, without accounting for patients’ pre-existing statin use or whether statins were continued postoperatively. This narrow definition of exposure overlooks potentially important temporal dynamics and pharmacologic effects related to chronic statin therapy. In contrast, emerging evidence suggests that inpatient statin use may reduce the risk of delirium in medically ill ICU patients ( 19 ), including those with heart failure ( 20 ) or chronic obstructive pulmonary disease ( 21 ). In these studies, statin exposure was defined as administration during hospitalization, rather than being limited to the perioperative period. A potential explanation for these inconsistent findings lies in the interaction between statin pharmacodynamics and the timing and duration of therapy. The anti-inflammatory effects of statins, including suppression of cytokine release and preservation of blood-brain barrier integrity, are thought to be dose- and time-dependent. Long-term statin users undergoing emergency cardiovascular surgery have been shown to have a lower risk of postoperative delirium, suggesting a cumulative benefit ( 22 ). Similarly, observational studies in patients with diabetic kidney disease have reported an inverse association between cumulative statin dose and delirium risk ( 23 ). On the other hand, abrupt discontinuation of statins—particularly in the context of critical illness—may exacerbate the inflammatory response and potentially precipitate delirium ( 24 ). The timing of statin initiation may also be critical. In patients with sepsis, early statin administration has been associated with a lower risk of delirium, possibly due to early attenuation of systemic inflammation ( 24 ). However, as sepsis progresses and inflammation becomes more widespread, the therapeutic window for neuroprotection may narrow, diminishing the potential benefit of delayed statin initiation. Systemic inflammation is a key driver of delirium, especially in critically ill patients. C-reactive protein (CRP) have been shown to correlate with delirium risk in surgical populations. Preoperative elevations in CRP are associated with higher postoperative delirium incidence ( 17 , 22 , 25 ), whereas patients receiving statin therapy prior to surgery often demonstrate lower CRP levels and correspondingly lower delirium incidence. These observations lend support to the hypothesis that the anti-inflammatory effects of statins play a central role in their potential to mitigate delirium, particularly when initiated early or maintained continuously in the peri-critical illness phase. In our study, the overall incidence of delirium among ICU patients with CKD was 29.2%, which aligns with the prevalence reported in critically ill populations, typically ranging from 20–50%. Delirium in CKD is a multifactorial condition. In older adults with renal dysfunction, the risk is amplified by a confluence of mechanisms, including the accumulation of uremic toxins, cerebral ischemia from vascular pathology, chronic inflammation, oxidative stress, anemia, and electrolyte disturbances ( 26 ). These patients often have reduced physiological reserve, making them more susceptible to fluctuations in cerebral perfusion and neurochemical imbalances. The risk is even more pronounced in individuals undergoing their first sessions of hemodialysis, where rapid fluid shifts, catheter-related complications, and dialysis disequilibrium syndrome can precipitate acute neurological events ( 27 ). Our findings suggest that the potential protective effect of statins against delirium is consistent across patients with varying levels of illness severity, as assessed by standard scoring systems such as SOFA, SAPS II, and OASIS. Subgroup analysis revealed no significant interaction between disease severity and the observed reduction in delirium risk, indicating that the benefit of statins may be broadly applicable regardless of baseline critical illness burden. Interestingly, prior studies have proposed that in patients with mild to moderate illness, statin therapy could paradoxically increase the risk of delirium ( 28 ). One hypothesized mechanism involves the disruption of cerebral autoregulation, whereby statins may interfere with the adaptive redistribution of cerebral blood flow in response to changing systemic demands, potentially compromising perfusion to the central nervous system. In such cases, the delicate balance between oxygen delivery and metabolic demand may be disturbed, leading to transient cognitive dysfunction.In contrast, among critically ill patients, systemic inflammation becomes the dominant pathological process driving delirium. In these settings, the anti-inflammatory and endothelial-stabilizing properties of statins may mitigate the inflammatory cascade implicated in delirium pathogenesis. Statins have been shown to reduce cytokine release, preserve blood-brain barrier integrity, and attenuate microglial activation, all of which may contribute to a reduced risk of neuroinflammation-induced delirium. Thus, while the effects of statins may vary depending on physiological context, our result suggest that in the setting of critical illness—where inflammatory injury predominates—their net impact is protective rather than harmful. Lipophilic statins, such as atorvastatin and simvastatin, are capable of crossing the blood-brain barrier and may exert more direct effects on central neuroinflammatory pathways compared to hydrophilic statins like pravastatin. Indeed, some studies have shown that hydrophilic statins like pravastatin may also reduce delirium risk ( 19 ), suggesting that other drug-specific or patient-specific factors may be at play. In our analysis, lipophilic statins may confer a more robust protective effect against the development of delirium in critically ill patients. Notably, this result diverges from most prior studies, which have generally found no significant advantage of lipophilic over hydrophilic statins in this context. A possible explanation for this discrepancy is the relatively small sample size in the hydrophilic statin group (n = 318), compared to the lipophilic (n = 1460) and non-statin groups (n = 1440), which may have limited the statistical power to detect a significant effect in the hydrophilic subgroup. These findings underscore the need for further mechanistic studies and comparative effectiveness research to better delineate the role of statin properties in neurocognitive outcomes. Delirium risk in ICU patients is also influenced by sedative exposure, particularly in those with renal impairment. Benzodiazepines, such as midazolam, are commonly used in the ICU but are known to increase delirium risk due to their sedative and amnestic effects. Midazolam is metabolized to an active compound, α-hydroxymidazolam, which is renally excreted and can accumulate in patients with impaired kidney function, leading to prolonged sedation and altered mental status ( 29 ). In our study, the protective effect of statins was evident in patients who received benzodiazepines. Whether this interaction is pharmacodynamic or immunomodulatory remains an open question deserving of further investigation. Beyond delirium, our study also demonstrated a significant association between statin use and lower 30-day and 90-day mortality in CKD patients. This is particularly important given that patients with advanced CKD often have limited physiological reserve and are at high risk for adverse outcomes during and after ICU admission. Prior research has shown that the occurrence of delirium in dialysis-dependent patients is independently associated with increased one-year mortality ( 27 ). Therefore, interventions that reduce the incidence of delirium may contribute not only to improved neurocognitive outcomes but also to enhanced survival in this population. Despite these encouraging findings, several limitations must be acknowledged. First, the data were derived from the MIMIC-IV database, which, although comprehensive, may suffer from incomplete baseline information and residual confounding. We attempted to mitigate this through propensity score matching and multivariable adjustment, but unmeasured variables such as nutritional status, frailty, or preexisting cognitive impairment could not be fully accounted for. Second, our study did not assess dose-response relationships or stratify outcomes by statin dose or duration of use. Given the potential for time-dependent effects of statins on inflammation and endothelial function, this represents an important area for future research. Third, we lacked reliable data on pre-hospital or long-term statin use, which limited our ability to explore how chronic exposure might influence delirium risk or mortality. Lastly, there was a high proportion of missing data regarding lipid profiles, which precludes any analysis of whether the association between statin use and delirium is mediated through lipid-lowering effects and we were unable to determine whether the degree of dyslipidemia or the magnitude of lipid reduction contributed to the observed outcomes. Conclusion In conclusion, our study adds to a growing body of evidence suggesting that statins may have a beneficial role in reducing delirium and improving short-term outcomes among critically ill patients with CKD. Further prospective studies and randomized controlled trials are warranted to validate these findings and to define the optimal statin regimen—including drug type, dose, and timing—for neuroprotection in this vulnerable population. Abbreviations chronic kidney disease (CKD), intensive care units (ICU), Confusion Assessment Method for the ICU (CAM-ICU), Propensity score matching (PSM), Mart for Intensive Care IV (MIMIC-IV),Institutional Review Board (IRB), Massachusetts Institute of Technology (MIT), International Classification of Diseases (ICD), heart rate (HR), mean blood pressure (MBP), respiratory rate (RR), congestive heart failure (CHF), coronary artery disease (CAD), Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease (CVD), hematocrit (HCT), hemoglobin (HGB), platelets (PLT), white blood cells (WBC), blood urea nitrogen (BUN), benzodiazepines (BZs), renal replacement treatment (RRT), mechanical ventilation (VEN), Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score II (SAPSII), Oxford acute severity of illness score (OASIS), Sequential Organ Failure Assessment (SOFA), Standardized mean differences (SMDs), Kaplan-Meier (KM), standardized mean differences (SMD), C-reactive protein (CRP). Declarations Competing interests The authors report there are no competing interests to declare. Ethics declarations The MIMIC-IV dataset was de-identified and approved by the Institutional Review Board (IRB) of the Massachusetts Institute of Technology (MIT), and it did not require informed consent. Given that no additional data collection was performed, no further ethical declaration was required for this study. Funding statement This work was supported by Science and Technology Projects in Guangzhou (2023A03J1011). Author Contribution F.L. conceived the project, Y.C. and T.L. analyzed the data, generated statistical table and plots and wrote the manuscript. Z.H. and X.W. conducted data collection and data interpretation and L.C. revised the article. All authors reviewed the manuscript. Acknowledgements Not appliable. Data availability statement Publicly available datasets were analyzed in this study. These data can be found at https://physionet.org/content/mimiciv/3.1/ . References Giannakou K, Golenia A, Liabeuf S, Malyszko J, Mattace-Raso F, Farinha A, et al. Methodological challenges and biases in the field of cognitive function among patients with chronic kidney disease. Frontiers in medicine. 2023;10:1215583. Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Critical care (London, England). 2008;12 Suppl 3(Suppl 3):S3. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet (London, England). 2014;383(9920):911–22. Davani AB, Snyder SH, Oh ES, Mears SC, Crews DC, Wang NY, et al. Kidney Function Modifies the Effect of Intraoperative Opioid Dosage on Postoperative Delirium. Journal of the American Geriatrics Society. 2021;69(1):191–6. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr., et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. Jama. 2004;291(14):1753–62. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. American journal of respiratory and critical care medicine. 2009;180(11):1092–7. Pépin M, Klimkowicz-Mrowiec A, Godefroy O, Delgado P, Carriazo S, Ferreira AC, et al. Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment. European journal of neurology. 2023;30(9):2899–911. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109(23 Suppl 1):Iii39-43. Yu XB, Zhang HN, Dai Y, Zhou ZY, Xu RA, Hu LF, et al. Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice. Journal of affective disorders. 2019;245:939–49. Liu P, Gao Q, Guan L, Hu Y, Jiang J, Gao T, et al. Atorvastatin attenuates surgery-induced BBB disruption and cognitive impairment partly by suppressing NF-κB pathway and NLRP3 inflammasome activation in aged mice. Acta biochimica et biophysica Sinica. 2021;53(5):528–37. Katznelson R, Djaiani GN, Borger MA, Friedman Z, Abbey SE, Fedorko L, et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology. 2009;110(1):67–73. Page VJ, Davis D, Zhao XB, Norton S, Casarin A, Brown T, et al. Statin use and risk of delirium in the critically ill. American journal of respiratory and critical care medicine. 2014;189(6):666–73. Vallabhajosyula S, Kanmanthareddy A, Erwin PJ, Esterbrooks DJ, Morrow LE. Role of statins in delirium prevention in critical ill and cardiac surgery patients: A systematic review and meta-analysis. Journal of critical care. 2017;37:189–96. Chang YH, Wang JY, Peng TR, Lian JH, Lee MC, Chen HM. Statin Use and Delirium Risk: An Updated Systematic Review and Meta-Analysis. American journal of therapeutics. 2023;30(4):e326-e35. van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. Journal of Statistical Software. 2011;45(3):1–67. Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Critical care medicine. 2001;29(7):1370–9. Redelmeier DA, Thiruchelvam D, Daneman N. Delirium after elective surgery among elderly patients taking statins. CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne. 2008;179(7):645–52. Mariscalco G, Cottini M, Zanobini M, Salis S, Dominici C, Banach M, et al. Preoperative statin therapy is not associated with a decrease in the incidence of delirium after cardiac operations. The Annals of thoracic surgery. 2012;93(5):1439–47. Mather JF, Corradi JP, Waszynski C, Noyes A, Duan Y, Grady J, et al. Statin and Its Association With Delirium in the Medical ICU. Critical care medicine. 2017;45(9):1515–22. Xia J, Wang L, Zhang N, Xu H. Association between delirium and statin use in patients with congestive heart failure: a retrospective propensity score-weighted analysis. Frontiers in aging neuroscience. 2023;15:1184298. Xia J, Hu C, Wang L, Zhang Y. Association between statin use on delirium and 30-day mortality in patients with chronic obstructive pulmonary disease in the intensive care unit. European journal of medical research. 2023;28(1):572. Lee DS, Lee MY, Park CM, Kim DI, Kim YW, Park YJ. Preoperative statins are associated with a reduced risk of postoperative delirium following vascular surgery. PloS one. 2018;13(3):e0192841. Sun M, Wang X, Lu Z, Yang Y, Lv S, Miao M, et al. Statins Reduce Delirium Risk in Older Adults With Type 2 Diabetes. Journal of the American Medical Directors Association. 2025;26(4):105490. Morandi A, Hughes CG, Thompson JL, Pandharipande PP, Shintani AK, Vasilevskis EE, et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Critical care medicine. 2014;42(8):1899–909. Qin X, Ren J, Xing C, Chen L, Wang R, Tian S. Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study. Frontiers in neurology. 2025;16:1516800. Kurella Tamura M, Yaffe K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international. 2011;79(1):14–22. Arai Y, Shioji S, Tanaka H, Kondo I, Sakamoto E, Suzuki M, et al. Delirium is independently associated with early mortality in elderly patients starting hemodialysis. Clinical and experimental nephrology. 2020;24(11):1077–83. An JY, Park JY, Cho J, Kim HE, Park J, Oh J. The Relationship between Delirium and Statin Use According to Disease Severity in Patients in the Intensive Care Unit. Clinical psychopharmacology and neuroscience: the official scientific journal of the Korean College of Neuropsychopharmacology. 2023;21(1):179–87. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. Jama. 2007;298(22):2644–53. Supplementary Materials Supplementary Materials are not available with this version. Additional Declarations No competing interests reported. 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09:51:43","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17426,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/7667e42f34483cc3c76f068c.png"},{"id":91842342,"identity":"f2f12a28-a9ea-49cc-9b5d-762eacc832c8","added_by":"auto","created_at":"2025-09-22 09:59:43","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21058,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/2772eb1a9c8d2d41dce15b3d.png"},{"id":91839491,"identity":"f470a8ba-e232-4383-b6ca-da5e33aa8bca","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":22660,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/1327bd89c51cfec160443734.png"},{"id":91839490,"identity":"3b8f065a-133b-4b83-a269-56b32dad8acb","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92522,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefig4.png","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/2825e1a0b303cf6f46a611bc.png"},{"id":91839494,"identity":"abe33386-4de6-419d-8b4d-d493a3281625","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"xml","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":138905,"visible":true,"origin":"","legend":"","description":"","filename":"a91644a6990f4e9194a79ad14f0162a01structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/9884317d211498625a3fb025.xml"},{"id":91839498,"identity":"f71ad73b-2d34-4bcc-9131-346c1b726abc","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"html","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":145807,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/bb643b514e9653ee81e8857a.html"},{"id":91839473,"identity":"df261eb2-4b37-4e0c-ab5d-8cfae0c0eb1a","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24348,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of cohort selection.\u003c/p\u003e","description":"","filename":"fig1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/2ef842dc39413cc6c86b0673.jpeg"},{"id":91842339,"identity":"8944ef00-13df-450b-961e-5bfe7bffd6da","added_by":"auto","created_at":"2025-09-22 09:59:43","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":70017,"visible":true,"origin":"","legend":"\u003cp\u003eKM survival curves of 30-day mortality within the ICU for patients in statin-exposure and Non-statin.\u003c/p\u003e","description":"","filename":"fig2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/bf7b08b40c1a7084a1fe92c0.jpeg"},{"id":91839476,"identity":"2c7131c5-a115-4017-b90a-0e468545377d","added_by":"auto","created_at":"2025-09-22 09:51:43","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":77546,"visible":true,"origin":"","legend":"\u003cp\u003eKM survival curves of 90-day mortality within the ICU for patients in statin-exposure and Non-statin.\u003c/p\u003e","description":"","filename":"fig3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/85f148e160f887c4d6991dbe.jpeg"},{"id":91843764,"identity":"06c6c4fb-d49b-4b52-a053-6fdf264ed5dc","added_by":"auto","created_at":"2025-09-22 10:07:43","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":403135,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the subgroup analysis of the association between statin and the incidence of delirium.\u003c/p\u003e","description":"","filename":"fig4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/e4608b97cda1ea8b2eb50f33.jpeg"},{"id":97178519,"identity":"ffec351a-1de2-4de0-be6c-d34b6b73da65","added_by":"auto","created_at":"2025-12-01 16:10:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1632015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7482282/v1/f81a8e82-8760-49ca-8300-f7c699fbc965.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Statin Use is Associated with Reduced Delirium and Improved Short- Term Outcomes in Critically Ill Patients with Chronic Kidney Disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCKD is a clinical syndrome characterized by a progressive decline in renal function. Diagnosis is based on criteria that include persistent (greater than three months) structural or functional renal abnormalities, sustained proteinuria or hematuria detected through urinalysis, and biochemical alterations such as metabolic imbalances of uremic toxins. CKD has become a major global health challenge, affecting approximately 850\u0026nbsp;million people worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Among its numerous systemic impacts, CKD has been increasingly recognized as a risk factor for cognitive dysfunction and neuropsychiatric complications, including delirium. The susceptibility may stem from the accumulation of neurotoxic uremic solutes and impaired clearance of medications such as sedatives (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and analgesics (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), especially during critical illness.\u003c/p\u003e\u003cp\u003eDelirium is a transient but severe neurocognitive disorder marked by an acute onset and fluctuating disturbance in attention, awareness, and cognition. It is commonly precipitated by acute illness, medications, or physiological stressors, and frequently occurs in hospitalized patients, particularly those in ICU. Incidence rates in ICU populations can exceed 60%, with even higher rates in high-risk groups such as the elderly and those with multiple comorbidities (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Importantly, delirium is independently associated with a variety of adverse outcomes, including prolonged mechanical ventilation, extended ICU and hospital stays, long-term cognitive impairment, and elevated short- and long-term mortality rates (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Despite its clinical significance, delirium is often underdiagnosed and lacks effective pharmacologic preventive strategies.\u003c/p\u003e\u003cp\u003ePatients with CKD are especially vulnerable to delirium, owing to factors such as metabolic dysregulation, anemia, polypharmacy, and systemic inflammation. The risk is further amplified in the ICU, where CKD patients frequently require complex interventions, are more prone to hemodynamic instability, and often experience acute-on-chronic kidney injury (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Observational studies have found that CKD is an independent risk factor for delirium in critically ill patients, with worse short-term and long-term outcomes (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Nevertheless, few studies have evaluated targeted interventions for delirium in this patient group, and the role of commonly used medications, such as statins, remains unclear.\u003c/p\u003e\u003cp\u003eStatins, or HMG-CoA reductase inhibitors, are widely prescribed for their lipid-lowering and cardiovascular protective effects. Beyond their primary indication, statins exhibit pleiotropic properties, including anti-inflammatory, immunomodulatory, and antioxidant effects, as well as enhancement of endothelial function (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). These effects are particularly relevant in the context of delirium, which is thought to arise from systemic inflammation and neuroinflammation. Simvastatin has been shown to reduce microglial activation, suppress proinflammatory cytokines, and improve cognitive function in lipopolysaccharide-induced neuroinflammation in mice (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Similarly, atorvastatin has demonstrated protective effects on the blood\u0026ndash;brain barrier and neuronal apoptosis in models of surgically induced encephalopathy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDespite this theoretical benefit, the clinical literature on statins and delirium remains inconclusive. Some observational studies and meta-analyses suggest a reduced risk of delirium with preadmission statin use, particularly in surgical and ICU populations (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Conversely, other studies report either no association or a potential increase in delirium risk, possibly due to statin-induced sleep disturbances, drug interactions, or effects on neuronal cholesterol metabolism (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). To date, no research has specifically examined the impact of statins on delirium incidence among patients with CKD, despite this population's elevated baseline risk and frequent statin use.\u003c/p\u003e\u003cp\u003eTo address this knowledge gap, the present study utilizes the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to investigate the association between statin use and delirium incidence among critically ill patients with CKD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData source\u003c/h2\u003e\u003cp\u003eThis retrospective study utilized data from the MIMIC-IV database (version 3.1), a publicly available single-center intensive care medicine database. The database encompasses comprehensive clinical data of patients admitted to the ICUs at Beth Israel Deaconess Medical Center in Boston, Massachusetts, spanning the years 2008 to 2019. This dataset includes detailed information on demographics, vital signs, laboratory tests, and treatment protocols. The MIMIC-IV dataset was de-identified and approved by the Institutional Review Board (IRB) of the Massachusetts Institute of Technology (MIT), and it did not require informed consent. Given that no additional data collection was performed, no further ethical declaration was required for this study. The research team was authorized to use the database by completing mandatory training programs and passing the corresponding examinations (certificate number: 59948527).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eMIMIC-IV (v3.1) documented 65366 cases of first-time ICU admissions. Patients diagnosed with CKD were identified using International Classification of Diseases, 9th Revision (ICD-9) or 10th Revision (ICD-10) codes. Exclusion criteria included: (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) ICU stay\u0026thinsp;\u0026lt;\u0026thinsp;72 hours; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) age\u0026thinsp;\u0026lt;\u0026thinsp;18 years; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) diagnosis without CKD and (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) absence of delirium assessments during ICU admission. Finally, 3218 eligible CKD patients were divided into the statin group (n\u0026thinsp;=\u0026thinsp;1778) and non-statin group (n\u0026thinsp;=\u0026thinsp;1440).\u003c/p\u003e\n\u003ch3\u003eData extraction and processing\u003c/h3\u003e\n\u003cp\u003eRaw data for CKD patients were extracted from MIMIC-IV (v3.1) using Navicat Premium (version 17.0), including demographics, vital signs, comorbidities, laboratory results, treatment interventions, disease severity scores. Vital signs included heart rate (HR), mean blood pressure (MBP), respiratory rate (RR). Comorbidities collected congestive heart failure (CHF), coronary artery disease (CAD), Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease (CVD), diabetes, cancer and CKD stage. Laboratory parameters included hematocrit (HCT), hemoglobin (HGB), platelets (PLT), white blood cells (WBC), anion gap, bicarbonate, chloride, potassium, sodium, blood urea nitrogen (BUN), calcium, creatinine, glucose. Vital signs and laboratory values were averaged over the first day of ICU admission. Treatment interventions included use of benzodiazepines (BZs), propofol, vasopressor (dopamine, norepinephrine, phenylephrine, vasopressin), cortisone, renal replacement treatment (RRT), mechanical ventilation (VEN), within 3 days of ICU admission. Disease severity was assess using the, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score II (SAPSII), Oxford acute severity of illness score (OASIS) and Sequential Organ Failure Assessment (SOFA) score. Variables with \u0026gt;\u0026thinsp;6% missing data were excluded (proportion of missing in each variables shown in Table S1), and remaining missing values were imputed using the \u0026lsquo;mice\u0026rsquo; package for multiple imputation (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eExposure and outcomes\u003c/h3\u003e\n\u003cp\u003ePatients were categorized into the statin group (statin use within 3 days of ICU admission) and non-statin group. The primary outcome was delirium incidence during ICU stay, while the secondary outcome was 30-day mortality. Delirium was diagnosed using the CAM-ICU (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), which requires meeting criteria 1 and 2 plus either 3 or 4: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) acute mental status change or fluctuating course; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) inattention; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) disorganized thinking; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) altered consciousness level. CAM-ICU assessments in MIMIC-IV were performed by trained healthcare professionals followed by above standards, with evaluations performed at least twice daily.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003ePatient characteristics were described overall and by group (statin vs. non-statin). Continuous variables were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (Interquartile range) based on normality and non-normality, with group comparisons using two independent samples student\u0026rsquo;s test or Mann-Whitney U tests. Categorical variables were presented as percentages and compared via chi-square tests.\u003c/p\u003e\u003cp\u003ePSM with a 1:1 ratio and caliper width of 0.1 was used to balance baseline characteristics. Standardized mean differences (SMDs) were used to evaluate the balance between groups, with an SMD of less than 0.1 generally indicating adequate covariate balance. Logistic regression was used to estimate statin exposure and delirium. The Kaplan-Meier (KM) curves depicted the temporal survival trends over 30 and 90 days in the statin and non-statin groups before and after PSM and log-rank tests was used to compared. Subgroup analyses stratified by age, gender, CHF, CAD, COPD, CVD, diabetes, cancer CKD stage, use of BZs and propofol, CCI, SAPSII, OASIS and SOFA.\u003c/p\u003e\u003cp\u003eAll analyses were conducted using R software (version 4.4.0; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and Z Statistical Platform (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.medsta.cn/software\u003c/span\u003e\u003cspan address=\"https://www.medsta.cn/software\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A two-tailed test was used, and p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristic\u003c/h2\u003e\u003cp\u003eAfter applying exclusion criteria, a total of 3218 first-time ICU-admitted CKD patients were included in the study, with 1440 (44.7%) in the non-statin group and 2263 (55.3%) in the statin group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e compares the baseline characteristics of ICU patients with CKD who received statin therapy versus those who did not, both before and after PSM.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristic.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c12\" namest=\"c8\"\u003e\u003cp\u003eAfter PSM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;3218)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNonstatin (n\u0026thinsp;=\u0026thinsp;1440)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStatin (n\u0026thinsp;=\u0026thinsp;1778)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;2132)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNonstatin (n\u0026thinsp;=\u0026thinsp;1066)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eStatin (n\u0026thinsp;=\u0026thinsp;1066)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.8 (65.5, 82.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73.0 (61.8, 82.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76.1 (68.2, 83.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.369\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e75.7 (66.9, 83.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e75.4 (66.5, 83.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e75.8 (67.4, 82.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.813\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (male %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2040 (63.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e856 (59.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1184 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.152\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1333 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e659 (61.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e674 (63.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.502\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVital sign\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHR (beats/min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.276\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e83.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e83.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e83.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.538\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRR (beats/min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.208\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e19.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e19.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e19.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.907\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75.1 (69.6, 82.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.5 (69.8, 83.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74.8 (69.4, 82.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.043\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e75.5 (69.8, 83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e75.7 (69.9, 83.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e75.3 (69.6, 82.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.358\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidity, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1769 (55.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e690 (47.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1079 (60.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.261\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1171 (54.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e579 (54.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e592 (55.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.571\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCAD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1364 (42.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e367 (25.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e997 (56.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.616\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e765 (35.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e364 (34.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e401 (37.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.095\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.072\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53 (3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.482\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e68 (3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e33 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e35 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.805\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e673 (20.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e279 (19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e394 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e476 (22.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e223 (20.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e253 (23.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.066\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1636 (50.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e620 (43.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1016 (57.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.285\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1055 (49.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e519 (48.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e536 (50.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.461\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e415 (13.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e247 (17.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e168 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.263\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e285 (13.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e152 (14.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e133 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.227\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e596 (18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e291 (20.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e305 (17.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e379 (17.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e191 (17.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e188 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.865\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLab events\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCT (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.275\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.900\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHGB (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.263\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.872\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e175.0 (128.0, 234.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e170.0 (118.0, 235.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e178.0 (135.0, 233.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e179.5 (133.5, 238.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e176.5 (128.5, 236.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e182.0 (137.6, 240.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.097\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.6 (8.5, 15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.8 (8.2, 15.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.5 (8.7, 15.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.597\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.161\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11.5 (8.3, 15.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11.6 (8.1, 15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11.5 (8.5, 15.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.593\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAniongap (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.5 (13.0, 18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.0 (13.5, 19.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.0 (12.5, 18.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e15.5 (13.0, 18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e15.5 (13.0, 18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e15.0 (13.0, 18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.466\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBicarbonate (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.746\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChloride (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e102.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e102.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e102.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e102.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e102.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.961\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePotassium (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.504\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.359\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSodium (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e138.0 (135.0, 141.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e138.0 (134.5, 141.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e138.0 (135.5, 140.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.276\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e138.0 (135.4, 141.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e138.0 (135.0, 141.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e138.0 (135.5, 140.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.239\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.063\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36.0 (24.1, 56.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.5 (26.0, 62.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.0 (23.0, 52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.230\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e36.5 (24.0, 57.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e37.5 (24.0, 58.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e35.5 (23.0, 56.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.246\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.5 (8.0, 8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.4 (7.94, 8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.5 (8.1, 8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.5 (8.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8.5 (8.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e8.5 (8.1, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.036\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.9 (1.4, 3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.1 (1.4, 3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.8 (1.4, 3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.9 (1.4, 3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.9 (1.4, 3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e1.9 (1.4, 3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.432\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlucose (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e136.5 (112.0, 178.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e136.5 (112.0, 179.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e136.3 (112.0, 177.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e137.0 (112.0, 179.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e138.0 (112.5, 178.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e136.0 (112.0, 181.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBZs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1782 (55.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e889 (61.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e893 (50.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.230\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1186 (55.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e596 (55.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e590 (55.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.794\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePropofol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1876 (58.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e810 (56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1066 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1188 (55.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e577 (54.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e611 (57.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVasopressor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e775 (24.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e383 (26.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e392 (22.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e509 (23.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e248 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e261 (24.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.509\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCortisone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e191 (6.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e101 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e90 (5.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e137 (6.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e75 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e62 (5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.251\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRRT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e804 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e407 (28.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e397 (22.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e500 (23.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e252 (23.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e248 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.838\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVEN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2012 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e894 (62.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1118 (62.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1303 (61.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e642 (60.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e661 (62.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.399\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScores\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.0 (7.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.0 (6.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.0 (7.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.190\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.0 (7.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8.0 (7.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e8.0 (7.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.528\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSAPSII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.0 (36.0, 53.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.0 (37.0, 56.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.0 (36.0, 52.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.165\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e43.5 (36.0, 53.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e44.0 (36.0, 54.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e43.0 (36.0, 53.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.583\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOASIS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.0 (29.0, 40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.0 (29.0, 42.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.0 (28.0, 39.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.178\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e34.0 (29.0, 40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e34.5 (29.0, 41.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e34.0 (29.0, 40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOFA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0 (4.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.294\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e6.0 (4.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.734\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEvents\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelirium, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e938 (29.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e496 (34.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e442 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e641 (30.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e366 (34.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e275 (25.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30-day Mortality, n( %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e776 (24.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e413 (28.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e363 (20.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e534 (25.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e293 (27.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e241 (22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-day Mortality, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1066 (33.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e567 (39.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e499 (28.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e729 (34.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e399 (37.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e330 (31.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"12\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;sd, medians (interquartile ranges), or numbers (percentages).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"12\"\u003eHR, heart rate; MBP, mean blood pressure; RR, respiratory rate; CHF, congestive heart failure; CAD: coronary artery disease; CVD, cerebrovascular disease; COPD: chronic obstructive pulmonary disease; HCT, hematocrit; HGB, hemoglobin; PLT, platelets; WBC, white blood cell count; BUN, blood urea nitrogen; BZs, benzodiazepines; RRT, renal replacement treatment; VEN, mechanical ventilation; CCI, Charlson Comorbidity index; SAPS II, Simplified Acute Physiology Score Index; OASIS, Oxford acute severity of illness score, SOFA, Sequential Organ Failure Assessment.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBefore PSM, significant differences were observed between the statin and non-statin groups. The statin group was older than non-stain (76.1 years vs. 73.0 years, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and there was a higher proportion of males in the statin group (66.6% vs. 59.4%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, patients in the statin group had a higher prevalence of comorbidities, including CHF, CAD, and COPD. Statin group had less use of BZs (50.2% vs. 61.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and more commonly used of propofol (60.0% vs. 56.3%, P\u0026thinsp;=\u0026thinsp;0.034). Patients in the statin group had a lower incidence of delirium (25.0% vs. 34.4%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than non-statin group, as well as lower 30-day mortality(20.4% vs. 28.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 90-day mortality rates (28.1% vs. 39.4%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eAfter PSM for non-outcome confounding factors, there were 1066 patients in each group. The standardized mean differences (SMD) for all variables were below 0.1, indicating successful matching and balance of covariates between two groups. Age and gender differences were no longer significant (P\u0026thinsp;=\u0026thinsp;0.813 and P\u0026thinsp;=\u0026thinsp;0.502, respectively), and comorbidities such as CHF, CAD, and COPD, which were more prevalent in the statin group before matching, showed no significant difference after matching (P\u0026thinsp;=\u0026thinsp;0.571, P\u0026thinsp;=\u0026thinsp;0.095, P\u0026thinsp;=\u0026thinsp;0.805, respectively). Patients using BZs and propofol show no difference statistically between groups with and without statin. However, after PSM, consistent with the results before PSM, patients in the statin-exposure patients remains showing a lower 30-day (22.6% vs. 27.5%, P\u0026thinsp;=\u0026thinsp;0.009) and 90-day mortality rates (31.0% vs. 37.4%, P\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssociation between statin and delirium in CKD patients\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the relationship between statin use and delirium incidence in ICU-admitted CKD patients, analyzed using logistic regression models both before and after PSM. Before PSM, the crude model showed a significantly negative association between statin use and delirium (OR: 0.63, 95% CI: 0.54\u0026ndash;0.73, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This negative association remained robust after adjusting for age and gender (Model 1: OR: 0.62, 95% CI: 0.53\u0026ndash;0.73, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and further adjustments for comorbidity (Model 2: OR: 0.54, 95% CI: 0.46\u0026ndash;0.64, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), vital sign, comorbidity, lab events, treatment, and disease severity scores (Model 3: OR: 0.63, 95% CI: 0.52\u0026ndash;0.76, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After PSM, statin use continued to show a significant negative correlation with delirium in all models, with the adjusted odds ratio in Model 3 being 0.60 (95% CI: 0.49\u0026ndash;0.74, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results consistently indicate that statin exposure is associated with a reduced risk of delirium in ICU patients, regardless of PSM or adjustment for various confounders.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRelationship between statin and the incidence of delirium in different models before and after propensity score matching.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-statin vs.Statin\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAfter PSM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCrude model\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63 (0.54\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.66 (0.55\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62 (0.53\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.67 (0.55\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.54 (0.46\u0026ndash;0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.66 (0.55\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63 (0.52\u0026ndash;0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.60 (0.49\u0026ndash;0.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 1: adjusted for age and gender; Model 2: adjusted for age, gender and comorbidity; Model 3: adjusted for age, gender, vital sign, comorbidity, lab events, treatment and disease severity scores.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAccording to the previous report, the properties of statins may influence the efficacy of the drug in preventing the occurrence of delirium. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, we further stratified the analysis based on the physicochemical properties of statins to examine their respective associations with the risk of delirium, using non-statin users as the reference group. Before PSM, both hydrophilic and lipophilic statins were associated with a significantly reduced risk of delirium. Specifically, hydrophilic statins showed an odds ratio (OR) of 0.69 (95% CI: 0.53\u0026ndash;0.91, P\u0026thinsp;=\u0026thinsp;0.008), while lipophilic statins demonstrated an even stronger association (OR: 0.62, 95% CI: 0.52\u0026ndash;0.72, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After PSM, the protective effect of lipophilic statins remained statistically significant, with an OR of 0.55 (95% CI: 0.44\u0026ndash;0.69, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, the association between hydrophilic statin use and delirium was attenuated and no longer reached statistical significance (OR: 0.83, 95% CI: 0.58\u0026ndash;1.20, P\u0026thinsp;=\u0026thinsp;0.271).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAnalysis of the relationship between statin properties and delirium.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAfter PSM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-statin vs. Hydrophilic statins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.69 (0.53\u0026ndash;0.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.83 (0.58\u0026ndash;1.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.271\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-statin vs. Lipophilic statins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62 (0.52\u0026ndash;0.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.55 (0.44\u0026ndash;0.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariable cox regression analysis before and after propensity score matching.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-statin vs.Statin\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAfter PSM\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHR, 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30-day mortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnivariate Cox logistic analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.69 (0.60\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.82 (0.69\u0026ndash;0.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultivariate Cox logistic analysis\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85 (0.73\u0026ndash;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.84 (0.71\u0026ndash;1.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-day mortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnivariate Cox logistic analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.67 (0.59\u0026ndash;0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.80 (0.69\u0026ndash;0.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultivariate Cox logistic analysis\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.80 (0.70\u0026ndash;0.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.81 (0.70\u0026ndash;0.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e1\u003c/sup\u003e: adjusted for age, gender, comorbidity, vital sign, lab events, treatment and disease severity scores.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eThe association of Statin Use with prognosis in CKD Patients\u003c/h2\u003e\u003cp\u003eBefore PSM, statin use was significantly associated with lower mortality rates. In the univariate analysis, the HR for 30-day mortality was 0.69 (95% CI: 0.60\u0026ndash;0.80, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and for 90-day mortality was 0.67 (95% CI: 0.59\u0026ndash;0.76, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These associations remain significant after adjusting for age, gender, comorbidity, vital sign, lab events, treatment and disease severity scores. For 30-day mortality, the HR was 0.85 (95% CI: 0.73\u0026ndash;0.99, P\u0026thinsp;=\u0026thinsp;0.035), and for 90-day mortality, the HR was 0.80 (95% CI: 0.70\u0026ndash;0.91, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eAfter PSM, the association between statin use and mortality remained significant, although the strength of the association was somewhat attenuated. For 30-day mortality, the HR was 0.82 (95% CI: 0.69\u0026ndash;0.97, P\u0026thinsp;=\u0026thinsp;0.019), and for 90-day mortality, the HR was 0.80 (95% CI: 0.69\u0026ndash;0.93, P\u0026thinsp;=\u0026thinsp;0.003). These associations show different in 30-day and 90-day mortality after adjusting for all the same factors. For 30-day mortality, the HR was 0.84 (95% CI: 0.71\u0026ndash;1.00, P\u0026thinsp;=\u0026thinsp;0.053), although this relationship is not statistically significant, it demonstrates a consistent trend, and for 90-day mortality, the HR was 0.80 (95% CI: 0.70\u0026ndash;0.94, P\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003e show Kaplan-Meier survival curves for 30-day and 90-day mortality risk model, respectively in statin and non-statin groups. Both figures clearly indicate that statin use is associated with significantly higher survival rates compared to the non-statin group. KM survival curves for the post-PSM risk model are shown in Additional file 1: Fig. S2 and S3 and remains significant in statin and non-statin group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSubgroup Analysis of Statin Use and Delirium Incidence\u003c/h2\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents a forest plot of the subgroup analysis examining the effect of statin use on the incidence of delirium across various patient subgroups. Overall, statin use was consistently associated with a lower incidence of delirium compared to the non-statin group.The protective effect of statins against delirium was observed across multiple subgroups, including patients with different comorbidities such as CHF, CAD, COPD, as well as varying severity scores like SAPS II and SOFA.The same trend was observed in subgroups based on the use of specific treatments, such as benzodiazepines or propofol. There is an interaction of statin use and delirium incidence between the BZs users and non-users(p\u0026thinsp;=\u0026thinsp;0.009). Compared to patients who did not use benzodiazepines, exposure to benzodiazepines may increase risk of delirium associated with statin use.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort study involving 3218 patients with CKD admitted to the ICU, we found that statin use was significantly associated with a lower incidence of delirium, as well as reduced 30-day and 90-day mortality. These associations remained consistent after adjusting for confounders and applying 1:1 propensity score matching. To our knowledge, it is the first study to specifically investigate the relationship between statin therapy and delirium among patients with CKD.\u003c/p\u003e\u003cp\u003eThe relationship between statin therapy and delirium remains controversial. A large retrospective analysis involving over 280000 patients aged 65 and older undergoing elective surgery suggested a higher incidence of postoperative delirium among those using statins (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, this study has several important limitations that warrant cautious interpretation. Despite its large sample size, the findings may be confounded by substantial baseline heterogeneity and unmeasured variables such as frailty, cognitive status, and medication adherence\u0026mdash;factors that are known to influence delirium risk but were not adequately controlled. Another retrospective study focusing on patients who underwent coronary artery bypass grafting reported a neutral effect of statin use on delirium (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Notably, both studies limited the exposure window to the period between hospital admission and the day prior to surgery, without accounting for patients\u0026rsquo; pre-existing statin use or whether statins were continued postoperatively. This narrow definition of exposure overlooks potentially important temporal dynamics and pharmacologic effects related to chronic statin therapy. In contrast, emerging evidence suggests that inpatient statin use may reduce the risk of delirium in medically ill ICU patients (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), including those with heart failure (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) or chronic obstructive pulmonary disease (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In these studies, statin exposure was defined as administration during hospitalization, rather than being limited to the perioperative period. A potential explanation for these inconsistent findings lies in the interaction between statin pharmacodynamics and the timing and duration of therapy.\u003c/p\u003e\u003cp\u003eThe anti-inflammatory effects of statins, including suppression of cytokine release and preservation of blood-brain barrier integrity, are thought to be dose- and time-dependent. Long-term statin users undergoing emergency cardiovascular surgery have been shown to have a lower risk of postoperative delirium, suggesting a cumulative benefit (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Similarly, observational studies in patients with diabetic kidney disease have reported an inverse association between cumulative statin dose and delirium risk (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). On the other hand, abrupt discontinuation of statins\u0026mdash;particularly in the context of critical illness\u0026mdash;may exacerbate the inflammatory response and potentially precipitate delirium (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The timing of statin initiation may also be critical. In patients with sepsis, early statin administration has been associated with a lower risk of delirium, possibly due to early attenuation of systemic inflammation (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, as sepsis progresses and inflammation becomes more widespread, the therapeutic window for neuroprotection may narrow, diminishing the potential benefit of delayed statin initiation. Systemic inflammation is a key driver of delirium, especially in critically ill patients. C-reactive protein (CRP) have been shown to correlate with delirium risk in surgical populations. Preoperative elevations in CRP are associated with higher postoperative delirium incidence (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), whereas patients receiving statin therapy prior to surgery often demonstrate lower CRP levels and correspondingly lower delirium incidence. These observations lend support to the hypothesis that the anti-inflammatory effects of statins play a central role in their potential to mitigate delirium, particularly when initiated early or maintained continuously in the peri-critical illness phase.\u003c/p\u003e\u003cp\u003eIn our study, the overall incidence of delirium among ICU patients with CKD was 29.2%, which aligns with the prevalence reported in critically ill populations, typically ranging from 20\u0026ndash;50%. Delirium in CKD is a multifactorial condition. In older adults with renal dysfunction, the risk is amplified by a confluence of mechanisms, including the accumulation of uremic toxins, cerebral ischemia from vascular pathology, chronic inflammation, oxidative stress, anemia, and electrolyte disturbances (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). These patients often have reduced physiological reserve, making them more susceptible to fluctuations in cerebral perfusion and neurochemical imbalances. The risk is even more pronounced in individuals undergoing their first sessions of hemodialysis, where rapid fluid shifts, catheter-related complications, and dialysis disequilibrium syndrome can precipitate acute neurological events (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur findings suggest that the potential protective effect of statins against delirium is consistent across patients with varying levels of illness severity, as assessed by standard scoring systems such as SOFA, SAPS II, and OASIS. Subgroup analysis revealed no significant interaction between disease severity and the observed reduction in delirium risk, indicating that the benefit of statins may be broadly applicable regardless of baseline critical illness burden. Interestingly, prior studies have proposed that in patients with mild to moderate illness, statin therapy could paradoxically increase the risk of delirium (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). One hypothesized mechanism involves the disruption of cerebral autoregulation, whereby statins may interfere with the adaptive redistribution of cerebral blood flow in response to changing systemic demands, potentially compromising perfusion to the central nervous system. In such cases, the delicate balance between oxygen delivery and metabolic demand may be disturbed, leading to transient cognitive dysfunction.In contrast, among critically ill patients, systemic inflammation becomes the dominant pathological process driving delirium. In these settings, the anti-inflammatory and endothelial-stabilizing properties of statins may mitigate the inflammatory cascade implicated in delirium pathogenesis. Statins have been shown to reduce cytokine release, preserve blood-brain barrier integrity, and attenuate microglial activation, all of which may contribute to a reduced risk of neuroinflammation-induced delirium. Thus, while the effects of statins may vary depending on physiological context, our result suggest that in the setting of critical illness\u0026mdash;where inflammatory injury predominates\u0026mdash;their net impact is protective rather than harmful.\u003c/p\u003e\u003cp\u003eLipophilic statins, such as atorvastatin and simvastatin, are capable of crossing the blood-brain barrier and may exert more direct effects on central neuroinflammatory pathways compared to hydrophilic statins like pravastatin. Indeed, some studies have shown that hydrophilic statins like pravastatin may also reduce delirium risk (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), suggesting that other drug-specific or patient-specific factors may be at play. In our analysis, lipophilic statins may confer a more robust protective effect against the development of delirium in critically ill patients. Notably, this result diverges from most prior studies, which have generally found no significant advantage of lipophilic over hydrophilic statins in this context. A possible explanation for this discrepancy is the relatively small sample size in the hydrophilic statin group (n\u0026thinsp;=\u0026thinsp;318), compared to the lipophilic (n\u0026thinsp;=\u0026thinsp;1460) and non-statin groups (n\u0026thinsp;=\u0026thinsp;1440), which may have limited the statistical power to detect a significant effect in the hydrophilic subgroup. These findings underscore the need for further mechanistic studies and comparative effectiveness research to better delineate the role of statin properties in neurocognitive outcomes.\u003c/p\u003e\u003cp\u003eDelirium risk in ICU patients is also influenced by sedative exposure, particularly in those with renal impairment. Benzodiazepines, such as midazolam, are commonly used in the ICU but are known to increase delirium risk due to their sedative and amnestic effects. Midazolam is metabolized to an active compound, α-hydroxymidazolam, which is renally excreted and can accumulate in patients with impaired kidney function, leading to prolonged sedation and altered mental status (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). In our study, the protective effect of statins was evident in patients who received benzodiazepines. Whether this interaction is pharmacodynamic or immunomodulatory remains an open question deserving of further investigation.\u003c/p\u003e\u003cp\u003eBeyond delirium, our study also demonstrated a significant association between statin use and lower 30-day and 90-day mortality in CKD patients. This is particularly important given that patients with advanced CKD often have limited physiological reserve and are at high risk for adverse outcomes during and after ICU admission. Prior research has shown that the occurrence of delirium in dialysis-dependent patients is independently associated with increased one-year mortality (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Therefore, interventions that reduce the incidence of delirium may contribute not only to improved neurocognitive outcomes but also to enhanced survival in this population.\u003c/p\u003e\u003cp\u003eDespite these encouraging findings, several limitations must be acknowledged. First, the data were derived from the MIMIC-IV database, which, although comprehensive, may suffer from incomplete baseline information and residual confounding. We attempted to mitigate this through propensity score matching and multivariable adjustment, but unmeasured variables such as nutritional status, frailty, or preexisting cognitive impairment could not be fully accounted for. Second, our study did not assess dose-response relationships or stratify outcomes by statin dose or duration of use. Given the potential for time-dependent effects of statins on inflammation and endothelial function, this represents an important area for future research. Third, we lacked reliable data on pre-hospital or long-term statin use, which limited our ability to explore how chronic exposure might influence delirium risk or mortality. Lastly, there was a high proportion of missing data regarding lipid profiles, which precludes any analysis of whether the association between statin use and delirium is mediated through lipid-lowering effects and we were unable to determine whether the degree of dyslipidemia or the magnitude of lipid reduction contributed to the observed outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study adds to a growing body of evidence suggesting that statins may have a beneficial role in reducing delirium and improving short-term outcomes among critically ill patients with CKD. Further prospective studies and randomized controlled trials are warranted to validate these findings and to define the optimal statin regimen\u0026mdash;including drug type, dose, and timing\u0026mdash;for neuroprotection in this vulnerable population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003echronic kidney disease (CKD), intensive care units (ICU), Confusion Assessment Method for the ICU (CAM-ICU), Propensity score matching (PSM), Mart for Intensive Care IV (MIMIC-IV),Institutional Review Board (IRB), Massachusetts Institute of Technology (MIT), International Classification of Diseases (ICD), heart rate (HR), mean blood pressure (MBP), respiratory rate (RR), congestive heart failure (CHF), coronary artery disease (CAD), Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease (CVD), hematocrit (HCT), hemoglobin (HGB), platelets (PLT), white blood cells (WBC), blood urea nitrogen (BUN), benzodiazepines (BZs), renal replacement treatment (RRT), mechanical ventilation (VEN), Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score II (SAPSII), Oxford acute severity of illness score (OASIS), Sequential Organ Failure Assessment (SOFA), Standardized mean differences (SMDs), Kaplan-Meier (KM), standardized mean differences (SMD), C-reactive protein (CRP).\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors report there are no competing interests to declare.\u003c/p\u003e\u003ch2\u003eEthics declarations\u003c/h2\u003e\u003cp\u003eThe MIMIC-IV dataset was de-identified and approved by the Institutional Review Board (IRB) of the Massachusetts Institute of Technology (MIT), and it did not require informed consent. Given that no additional data collection was performed, no further ethical declaration was required for this study.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding statement\u003c/h2\u003e\u003cp\u003eThis work was supported by Science and Technology Projects in Guangzhou (2023A03J1011).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF.L. conceived the project, Y.C. and T.L. analyzed the data, generated statistical table and plots and wrote the manuscript. Z.H. and X.W. conducted data collection and data interpretation and L.C. revised the article. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eNot appliable.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e\u003cp\u003ePublicly available datasets were analyzed in this study. These data can be found at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://physionet.org/content/mimiciv/3.1/\u003c/span\u003e\u003cspan address=\"https://physionet.org/content/mimiciv/3.1/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGiannakou K, Golenia A, Liabeuf S, Malyszko J, Mattace-Raso F, Farinha A, et al. Methodological challenges and biases in the field of cognitive function among patients with chronic kidney disease. Frontiers in medicine. 2023;10:1215583.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGirard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Critical care (London, England). 2008;12 Suppl 3(Suppl 3):S3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet (London, England). 2014;383(9920):911\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDavani AB, Snyder SH, Oh ES, Mears SC, Crews DC, Wang NY, et al. Kidney Function Modifies the Effect of Intraoperative Opioid Dosage on Postoperative Delirium. Journal of the American Geriatrics Society. 2021;69(1):191\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEly EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr., et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. Jama. 2004;291(14):1753\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. American journal of respiratory and critical care medicine. 2009;180(11):1092\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eP\u0026eacute;pin M, Klimkowicz-Mrowiec A, Godefroy O, Delgado P, Carriazo S, Ferreira AC, et al. Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment. European journal of neurology. 2023;30(9):2899\u0026ndash;911.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDavignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109(23 Suppl 1):Iii39-43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu XB, Zhang HN, Dai Y, Zhou ZY, Xu RA, Hu LF, et al. Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice. Journal of affective disorders. 2019;245:939\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu P, Gao Q, Guan L, Hu Y, Jiang J, Gao T, et al. Atorvastatin attenuates surgery-induced BBB disruption and cognitive impairment partly by suppressing NF-κB pathway and NLRP3 inflammasome activation in aged mice. Acta biochimica et biophysica Sinica. 2021;53(5):528\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKatznelson R, Djaiani GN, Borger MA, Friedman Z, Abbey SE, Fedorko L, et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology. 2009;110(1):67\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePage VJ, Davis D, Zhao XB, Norton S, Casarin A, Brown T, et al. Statin use and risk of delirium in the critically ill. American journal of respiratory and critical care medicine. 2014;189(6):666\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVallabhajosyula S, Kanmanthareddy A, Erwin PJ, Esterbrooks DJ, Morrow LE. Role of statins in delirium prevention in critical ill and cardiac surgery patients: A systematic review and meta-analysis. Journal of critical care. 2017;37:189\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChang YH, Wang JY, Peng TR, Lian JH, Lee MC, Chen HM. Statin Use and Delirium Risk: An Updated Systematic Review and Meta-Analysis. American journal of therapeutics. 2023;30(4):e326-e35.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. Journal of Statistical Software. 2011;45(3):1\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEly EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Critical care medicine. 2001;29(7):1370\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRedelmeier DA, Thiruchelvam D, Daneman N. Delirium after elective surgery among elderly patients taking statins. CMAJ: Canadian Medical Association journal\u0026thinsp;=\u0026thinsp;journal de l'Association medicale canadienne. 2008;179(7):645\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMariscalco G, Cottini M, Zanobini M, Salis S, Dominici C, Banach M, et al. Preoperative statin therapy is not associated with a decrease in the incidence of delirium after cardiac operations. The Annals of thoracic surgery. 2012;93(5):1439\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMather JF, Corradi JP, Waszynski C, Noyes A, Duan Y, Grady J, et al. Statin and Its Association With Delirium in the Medical ICU. Critical care medicine. 2017;45(9):1515\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXia J, Wang L, Zhang N, Xu H. Association between delirium and statin use in patients with congestive heart failure: a retrospective propensity score-weighted analysis. Frontiers in aging neuroscience. 2023;15:1184298.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXia J, Hu C, Wang L, Zhang Y. Association between statin use on delirium and 30-day mortality in patients with chronic obstructive pulmonary disease in the intensive care unit. European journal of medical research. 2023;28(1):572.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee DS, Lee MY, Park CM, Kim DI, Kim YW, Park YJ. Preoperative statins are associated with a reduced risk of postoperative delirium following vascular surgery. PloS one. 2018;13(3):e0192841.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSun M, Wang X, Lu Z, Yang Y, Lv S, Miao M, et al. Statins Reduce Delirium Risk in Older Adults With Type 2 Diabetes. Journal of the American Medical Directors Association. 2025;26(4):105490.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorandi A, Hughes CG, Thompson JL, Pandharipande PP, Shintani AK, Vasilevskis EE, et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Critical care medicine. 2014;42(8):1899\u0026ndash;909.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQin X, Ren J, Xing C, Chen L, Wang R, Tian S. Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study. Frontiers in neurology. 2025;16:1516800.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKurella Tamura M, Yaffe K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international. 2011;79(1):14\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArai Y, Shioji S, Tanaka H, Kondo I, Sakamoto E, Suzuki M, et al. Delirium is independently associated with early mortality in elderly patients starting hemodialysis. Clinical and experimental nephrology. 2020;24(11):1077\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAn JY, Park JY, Cho J, Kim HE, Park J, Oh J. The Relationship between Delirium and Statin Use According to Disease Severity in Patients in the Intensive Care Unit. Clinical psychopharmacology and neuroscience: the official scientific journal of the Korean College of Neuropsychopharmacology. 2023;21(1):179\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. Jama. 2007;298(22):2644\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Supplementary Materials","content":"\u003cp\u003eSupplementary Materials are not available with this version.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7482282/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7482282/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eDelirium is a common and serious neurocognitive complication in critically ill patients, particularly those with chronic kidney disease (CKD), who are predisposed due to systemic inflammation, metabolic dysregulation, and polypharmacy. Statins, widely used for their cardiovascular benefits, also possess anti-inflammatory and neuroprotective properties that may influence delirium risk. However, their impact on delirium incidence and short-term prognosis in CKD patients remains unclear.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective cohort study using the MIMIC-IV database, identifying 3218 adult patients with CKD admitted to the intensive care units (ICU). Patients were stratified based on statin exposure during the three days before and after ICU admission. The primary outcome was the incidence of delirium, which was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Secondary outcomes included all-cause mortality at 30 days and 90 days. Propensity score matching (PSM) was employed to balance baseline characteristics, and multivariable logistic and Cox regression models were utilized to estimate associations.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eBefore matching, statin use was associated with significantly lower delirium incidence (25.0% vs. 34.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and lower 30-day mortality (20.4% vs. 28.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After 1:1 PSM (n\u0026thinsp;=\u0026thinsp;2132), these associations remained significant: statin use correlated with reduced odds of delirium (adjusted OR 0.60, 95% CI: 0.49\u0026ndash;0.74, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and lower 30-day (HR 0.82, 95% CI: 0.69\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.019) and 90-day mortality (HR 0.80, 95% CI: 0.69\u0026ndash;0.93, p\u0026thinsp;=\u0026thinsp;0.003). Subgroup analyses showed consistent findings across CKD stages and comorbidity profiles, with notable interaction observed in benzodiazepine users (interaction for p\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eAmong critically ill patients with CKD, statin use is independently associated with a lower risk of delirium and improved short-term survival. These findings support the potential neuroprotective role of statins in this high-risk population and warrant further investigation through prospective studies and randomized controlled trials.\u003c/p\u003e","manuscriptTitle":"Statin Use is Associated with Reduced Delirium and Improved Short- Term Outcomes in Critically Ill Patients with Chronic Kidney Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 09:51:38","doi":"10.21203/rs.3.rs-7482282/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-25T19:26:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-21T05:31:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-17T13:54:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-17T12:23:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-16T14:35:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239246324439468448927056536283496973736","date":"2025-09-16T14:00:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58920308387862492551844730533072647152","date":"2025-09-15T12:05:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"262528234799859025623413396989956248661","date":"2025-09-13T14:29:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"122387494347609614423278260410569409446","date":"2025-09-12T10:49:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283247179064907733787353582664492396615","date":"2025-09-11T12:24:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-11T12:07:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-09T06:47:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-03T10:42:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2025-08-28T16:40:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a3e165a-60cf-4b57-826c-8db3c3b3acf4","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:03:05+00:00","versionOfRecord":{"articleIdentity":"rs-7482282","link":"https://doi.org/10.1186/s40001-025-03419-0","journal":{"identity":"european-journal-of-medical-research","isVorOnly":false,"title":"European Journal of Medical Research"},"publishedOn":"2025-11-27 15:57:19","publishedOnDateReadable":"November 27th, 2025"},"versionCreatedAt":"2025-09-22 09:51:38","video":"","vorDoi":"10.1186/s40001-025-03419-0","vorDoiUrl":"https://doi.org/10.1186/s40001-025-03419-0","workflowStages":[]},"version":"v1","identity":"rs-7482282","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7482282","identity":"rs-7482282","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}