The effect of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery:a secondary analysis of multicenter prospective data

The effect of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery:a secondary analysis of multicenter prospective data | 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 The effect of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery:a secondary analysis of multicenter prospective data Hai-yue Ma, Xue-cai Lv, Chen Zhang, Zhuo-ning Zhang, Xin-yu Hao, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6987226/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Purpose Against the backdrop of global population aging, the number of elderly patients undergoing surgical procedures continues to increase. These patients frequently experience postoperative acute pain and delirium, however, there is little clinical data on their possible interrelationships. Methods A secondary analysis of multicenter prospective data, including tertiary hospitals in Five Chinese Regions, from April 2020 to April 2022 .Elderly patients (≥ 65 years) scheduled for elective abdominal surgery under general anesthesia, without auditory, visual, or cognitive impairments, who completed assessments for postoperative delirium, anxiety, and depression.The impact of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery was evaluated using univariate and multivariate logistic regression, propensity score matching, and subgroup analysis. Results This study included 2,674 patients. Delirium occurred in 13.2% (n = 354) of patients in postoperative 7 days (POD 7), with significantly higher prevalence in the moderate-to-severe pain group (unadjusted: 16.3 vs. 9.6%, P < 0.001). Moderate-to-severe pain on POD1 showed a significant association with delirium occurrence in POD 7 according to univariate logistic regression (OR 1.831, 95% CI 1.445 to 2.319, P < 0.001), multivariable logistic regression (OR 1.629, 95% CI 1.274 to 2.084, P < 0.001), and propensity score matching (PSM) model (OR 1.443, 95% CI 1.108 to 1.879, P = 0.006). Conclusion In elderly patients undergoing elective abdominal surgery, moderate-to-severe pain on POD 1 was significantly associated with both delirium and depressive symptoms within 7 days of surgery. Improved early postoperative analgesic strategies may aid in preventing delirium. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT06964893 (2025-05-07 ) delirium elderly patients postoperative acute pain abdominal surgery Figures Figure 1 Figure 2 Figure 3 Key Summary Points Aim: This study aimed to investigate the impact of moderate-to-severe acute pain on postoperative day 1 (POD1) on delirium in elderly patients undergoing abdominal surgery. Findings: In elderly patients undergoing elective abdominal surgery, moderate-to-severe pain on POD 1 was significantly associated with both delirium and depressive symptoms within 7 days of surgery. Message: Adequate management of early postoperative acute pain may help prevent postoperative delirium in elderly patients. Introduction Delirium, a prevalent and severe postoperative complication in elderly patients, is clinically characterized by attention deficits, impaired consciousness, and disturbances in orientation, memory, and perception [ 1 ] . The incidence of delirium following non-cardiac surgeries ranges from 13 to 50% [ 2 ] , with abdominal surgery specifically associated with a 21% incidence rate [ 3 ] . Delirium leads to multiple adverse outcomes including prolonged hospitalization, diminished quality of life, persistent cognitive decline, increased postoperative morbidity, elevated healthcare expenditures, and higher risk of mortality [ 4 , 5 ] . Furthermore, postoperative negative emotional states such as anxiety and depression frequently occur in elderly surgical patients, significantly compromising clinical outcomes. Postoperative pain management remains a significant clinical challenge despite advancements in surgical and anesthetic techniques. The incidence of moderate-to-severe acute postoperative pain persists at elevated levels, with studies reporting rates reaching 50% in some populations [ 6 ] . This is particularly concerning given the established association between pain and delirium in elderly surgical patients - a combination that frequently leads to adverse outcomes in the absence of timely prevention, diagnosis, and intervention. There is also emerging evidence of interconnections between pain, anxiety, and depression. Early postoperative acute pain is a modifiable and clinically significant indicator. Effective pain management strategies may therefore serve as preventive measures against delirium, anxiety, and depression in geriatric surgical patients. Consequently, investigating the impact of early acute postoperative pain on delirium development and postoperative anxiety or depression symptoms holds significant clinical importance for optimizing peri-operative analgesia protocols and enhancing clinical outcomes in elderly surgical patients. This study will provide critical theoretical foundations for further optimizing comprehensive postoperative management protocols for elderly patients. Methods Study design and cohort This multicenter secondary analysis of prospective data included elderly patients who underwent elective abdominal surgery between April 2020 and April 2022 across five provinces or municipalities in China (Guizhou, Nanjing, Hunan, Hubei, and Beijing). Clinical data were systematically collected for analysis. The inclusion criteria were as follows: age ≥ 65 years; absence of auditory, visual, or cognitive impairments (operationally defined as a Chinese version of the Mini-Mental State Examination [MMSE] score ≤ 17); scheduled for elective abdominal surgery under general anesthesia with endotracheal intubation; complete assessments for postoperative delirium, anxiety, and depression. Patients were excluded if they met any of the following criteria: history of severe psychiatric disorders or chronic use of psychotropic medications (n = 715) ;NOTES: natural orifice transluminal endoscopic surgery (n = 454); vascular interventional procedures (n = 44); postoperative transfer to the intensive care unit (ICU) or death within 7 days after surgery (n = 1). Data collection We collected baseline characteristics and demographic data of the patients, including clinical information in the following areas: (1) Baseline characteristics: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status score, smoking, alcohol consumption, preoperative history of chronic pain, and comorbidities (hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, hepatic insufficiency, and renal insufficiency). (2) Pre-operative laboratory tests (the most recent prior to surgery): haemoglobin(Hb), white blood cell count, serum albumin. (3) Preoperative psychological assessments: anxiety and depression state evaluations. (4) Intra-operative variables: grade of operation, type of surgery, duration of surgery, transfusion, blood loss, intra-operative dexmedetomidine and nonsteroidal anti-inflammatory drugs (NSAIDs), drain, and patient-controlled intravenous analgesia (PCIA). Sample size Statistical analyses were performed using PASS version 15.0. Based on an anticipated 4.7% intergroup difference in delirium incidence, with a two-sided α level of 0.05 and 80% power (β = 0.20), our preliminary sample size calculation indicated a minimum requirement of 733 patients per group [ 7 ] . The final cohort of 2,674 patients included in our study clearly exceeded this minimal threshold, ensuring adequate statistical power. Exposure In this study, we defined the presence or absence of moderate-to-severe pain on POD1 as the exposure variable, assessed using the numerical rating scale (NRS) [ 8 ] . An NRS score < 4 on POD1 was classified as mild pain, while a score ≥ 4 indicated moderate-to-severe pain. Based on this exposure variable, patients were stratified into the mild pain group (NRS < 4) and moderate-to-severe pain group (NRS ≥ 4). Outcomes The primary outcomes were the incidence of delirium and its subtypes during POD 7. Delirium was assessed by trained staff using the 3D-CAM scale at bedside [ 9 ] . Assessments were conducted twice daily (in the morning and afternoon) throughout the postoperative period. The secondary outcomes included the incidence and subtypes of anxiety or depression symptoms. Trained assessors evaluated postoperative anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, administered at the patient's bedside during the recovery period [ 10 ] . A score > 5 was defined as indicating anxiety symptoms, with scores of 5–8 indicating mild symptoms, 9–14 representing moderate anxiety, and 15–21 reflecting severe anxiety. Postoperative depressive symptoms were assessed by trained researchers using the validated Chinese version of the Patient Health Questionnaire-9 (PHQ-9) at the patient's bedside [ 11 ] . A score > 5 was defined as indicating depressive symptoms, with scores of 5–9 representing mild symptoms and 10–14 indicating moderate depression. A score of 15–27 was classified as moderate-to-severe depression. These psychological assessments were conducted once during the postoperative hospitalization period, scheduled between postoperative days 3–7. For patients discharged before completing all assessments (delirium, anxiety, or depression), trained researchers performed standardized telephone follow-up evaluations using the same assessment protocols. Statistical analysis We descriptively summarized patient characteristics stratified by the presence or absence of moderate-to-severe pain. Continuous variables were reported as means ± standard deviation for normally distributed data or median (interquartile range) for non-normally distributed data, with between-group comparisons performed using Student's t -test or the Mann-Whitney U test, respectively. Categorical variables were summarized as frequencies (percentages) and analyzed using Pearson's chi-squared test. Univariate and multivariate regression analyses were performed to examine the relationship between acute pain and the incidence of early delirium. In the multivariate logistic regression model, a forced-entry method was applied, incorporating all predefined covariates. Variable selection for adjustment was guided by univariate screening and clinical plausibility regarding their association with delirium. To enhance the robustness of our findings, we performed PSM followed by subgroup analyses [ 12 ] . We adjusted for covariates exhibiting a standardized mean difference (SMD) > 0.2 between the mild and moderate-to-severe pain cohorts.Both the exposed and unexposed groups comprised 1,072 participants each. Post-matching balance was confirmed by achieving an SMD < 0.2 for all included variables, indicating well-balanced baseline characteristics. Statistical significance was defined as a two-sided P -value of < 0.05. All statistical analyses were performed using the R software (version 4.0.1; R Foundation for Statistical Computing, Vienna, Austria). Results We initially enrolled 3,389 patients aged 65 years or older. After excluding 715 patients based on the listed criteria, 2,674 were ultimately included in the analysis (Fig. 1 ). The median age was 70 years (interquartile range [IQR]: 67–74), and 627 (23.4%) patients were aged ≥ 75 years. Notably, the patients (1,779; 66.5%) were male. The overall incidence rate of delirium in this cohort was 13.2%. Patients were stratified into mild pain and moderate-to-severe pain groups. Significant differences ( P < 0.05) were observed between the groups in terms of ASA classification, surgical type, operative duration, drain, intra-operative dexmedetomidine, NSAIDs, and PCIA. Other variables showed no statistical differences. Compared with the mild pain group, a higher percentage of patients in the moderate-to-severe pain group had lower ASA classification, smoked, consumed alcohol, had low hemoglobin, preoperative anxiety, preoperative depression, open surgeries, prolonged operative time, drain, non-use of dexmedetomidine, NSAIDs, and PCIA (Table 1 ). Table 1 Characteristics of the primary cohort before and after matching Variable Before PSM (n = 2674) After PSM (n = 2144) Total Mild pain(n = 1210) Moderate-severe pain (n = 1464) P SMD Mild pain(n = 1072) Moderate-severe pain (n = 1072) P SMD Preoperative variables Age (median [interquartile range]), yr 70.00 [67.00 to 74.00] 71.00 [67.00 to 74.00] 70.00 [67.00 to 74.00] 0.486 0.039 71.00 [68.00 to 74.00] 70.00 [67.00 to 74.00] 0.510 0.027 Male, n (%) 1779 (66.5) 808 (66.8) 971 (66.3) 0.805 0.010 696 (64.9) 724 (67.5) 0.201 0.056 BMI (median [interquartile range]), kg/m² 24.10 [22.08 to 25.68] 24.10 [22.25 to 25.67] 24.03 [21.97 to 25.68] 0.073 0.060 24.10 [22.29 to 25.77] 24.10 [22.04 to 25.61] 0.156 0.048 ASA*, n (%) < 0.001 0.225 1.000 0.000 Ⅰ/Ⅱ 1899 (71.0) 795 (65.7) 1104 (75.4) 768 (71.6) 768 (71.6) Ⅲ/Ⅴ 775 (29.0) 415 (34.3) 360 (24.6) 304 (28.4) 304 (28.4) Comorbidity, n (%) 0.560 0.023 0.960 0.002 <2 2034 (76.1) 914 (75.5) 1120 (76.5) 816 (76.1) 817 (76.2) ≥ 2 640 (23.9) 296 (24.5) 344 (23.5) 256 (23.9) 255 (23.8) Smoke, n (%) 745 (27.86) 306 (25.29) 439 (29.99) 0.007 0.103 274 (25.6) 332 (31.0) 0.005 0.117 Alcohol, n (%) 710 (26.6) 297 (24.6) 413 (28.2) 0.033 0.081 271 (25.3) 309 (28.8) 0.065 0.078 Preoperative chronic pain, n (%) 88 (3.3) 48 (4.0) 40 (2.7) 0.075 0.076 44 (4.1) 22 (2.0) 0.006 0.145 Preoperative evaluation with scales Preoperative anxiety, n (%) 1025 (38.3) 452 (37.4) 573 (39.1) 0.345 0.037 392 (36.6) 427 (39.8) 0.120 0.067 Preoperative depression, n (%) 775 (29.0) 330 (27.3) 445 (30.4) 0.076 0.068 289 (27.0) 330 (30.8) 0.051 0.083 Preoperative laboratory examinations Haemoglobin, g dl-1, n (%) 0.018 0.092 0.318 0.043 <13.0 1470 (55.0) 635 (52.5) 835 (57.0) 575 (53.6) 598 (55.8) ≥ 13.0 1204 (45.0) 575 (47.5) 629 (43.0) 497 (46.4) 474 (44.2) Albumin (median [interquartile range]), g/L 39.70 [37.10 to 41.90] 39.70 [37.20 to 41.80] 39.70 [37.00 to 42.00] 0.960 0.006 39.90 [37.30 to 41.92] 40.00 [37.20 to 42.10] 0.517 0.024 WBC count(median [interquartile range]), mmol/L 5.73 [4.68 to 6.79] 5.73 [4.64 to 6.80] 5.74 [4.71 to 6.77] 0.778 0.012 5.70 [4.61 to 6.72] 5.78 [4.69 to 6.80] 0.354 0.031 Surgical/Anesthetic parameters Grade of operation, n (%) 0.494 0.027 0.965 0.002 <3 1020 (38.1) 453 (37.4) 567 (38.7) 429 (40.0) 428 (40.0) ≥ 3 1654 (61.9) 757 (62.6) 897 (61.3) 643 (60.0) 644 (60.1) Type of surgical*, n (%) < 0.001 0.221 0.043 0.092 Minimally invasive 2210 (82.6) 1060 (87.6) 1150 (78.6) 922 (86.0) 953 (89.0) Open 464 (17.4) 150 (12.4) 314 (21.4) 150 (14.0) 119 (11.1) Duration of surgery,min, n (%) 0.003 0.114 0.062 0.080 <180 1439 (53.8) 689 (57.0) 750 (51.2) 618 (57.7) 575 (53.6) ≥ 180 1235 (46.2) 521 (43.0) 714 (48.8) 454 (42.4) 497 (46.4) Blood loss (median [interquartile range]), ml 100.00 [50.00 to 116.00] 100.00 [50.00 to 116.00] 100.00 [50.00 to 116.00] 0.555 0.013 100.00 [30.00 to 116.00] 100.00 [50.00 to 116.00] 0.387 0.019 Blood transfusion, n (%) 240 (8.98) 117 (9.67) 123 (8.41) 0.256 0.045 103 (9.6) 103 (9.6) 1.000 0.000 Intraoperative medication Dexmedetomidine*, n (%) 659 (24.6) 355 (29.3) 304 (20.8) < 0.001 0.211 244 (22.8) 225 (21.0) 0.321 0.044 NSAIDs, n (%) 1420 (53.1) 609 (50.3) 811 (55.4) 0.009 0.102 567 (52.9) 581 (54.2) 0.544 0.026 PCIA*, n (%) 1326 (49.6) 498 (41.2) 828 (56.6) < 0.001 0.311 498 (46.5) 533 (49.2) 0.130 0.065 Drain, n (%) 2292 (85.7) 1011 (83.6) 1281 (87.5) 0.004 0.119 887 (82.7) 918 (85.6) 0.067 0.082 The data are shown as the median [interquartile range], n (%). Abbreviations: SMD, standardized mean difference; PSM, propensity score matching; BMI, body mass index; ASA, American Society of Anesthesiologists Physical status classification system; WBC, white blood cell; NSAIDs, non-steroidal anti-inflammatory drugs; PCIA, patient - controlled intravenous analgesia. *Variables included in the Propensity score. We used four logistic regression models to analyze the association between moderate-to-severe acute postoperative pain and delirium on POD 1 in elderly patients. In the univariate analysis, moderate-to-severe acute pain was significantly associated with an increased risk of delirium (OR = 1.831, 95% CI: 1.445 to 2.319, P < 0.001). The univariate logistic regression results are presented in Supplementary Table 1. In all multivariable regression models, moderate-to-severe acute pain remained an independent risk factor for delirium: Model Ⅱ OR = 1.823 (95% CI: 1.434 to 2.317, P < 0.001); Model Ⅲ OR = 1.613 (95% CI: 1.266 to 2.055, P < 0.001); Model Ⅳ OR = 1.629 (95% CI: 1.274 to 2.084, P < 0.001); Model PSM OR = 1.443 (95% CI: 1.108 to 1.879, P = 0.006) (Table 2 ). The detailed specifications of each model are provided in Supplementary Table 2. Table 2 Association between postoperative day 1: moderate-severe acute pain and delirium with logistic regression models and propensity score matching ( PSM ) analysis OR 95% CI P Model 1 a 1.831 1.445–2.319 < 0.001 Model 2 b 1.823 1.434–2.317 < 0.001 Model 3 c 1.613 1.266–2.055 < 0.001 Model 4 d 1.629 1.274–2.084 < 0.001 Model PSM (n = 2144) 1.443 1.108–1.879 0.006 a Model 1 a univariate logistic regression analysis. b Model 2 adjusted for age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status score, smoking, alcohol consumption, preoperative history of chronic pain, and comorbidity, hemoglobin (Hb), white blood cell count, serum albumin,preoperative psychological assessments: anxiety and depression state evaluations. c Model 3 adjusted for grade of operation, type of surgery, duration of surgery, transfusion, blood loss, intraoperative dexmedetomidine, nonsteroidal anti-inflammatory drugs (NSAIDs), drain, patient-controlled intravenous analgesia (PCIA). d Model 4 adjusted for model 2 plus model 3. e Model PSM a multivariable logistic regression. PSM was performed at a 1:1 ratio to balance the baseline covariates. Variables with an SMD > 0.2 (ASA classification, surgical type, intra-operative dexmedetomidine, PCIA) were matched between the mild and moderate-to-severe pain groups. Kernel density plots illustrated the propensity score (PS) distributions before and after matching (Fig. 2 ). Post-matching, each group comprised 1,072 patients, with all baseline characteristics balanced (SMD < 0.2; Table 1 ). Within the first 7 postoperative days, the incidence of delirium was significantly higher in the moderate-to-severe pain group compared to the mild pain group (16.3 vs. 9.6%, P < 0.001). Among delirium subtypes, significant differences were observed in hypoactive delirium (13.6 vs. 8.5%) and mixed-type delirium (4.5 vs. 1.7%). After 1:1 PSM (n = 2,144), the association between moderate-to-severe pain and delirium remained significant (15.0 vs. 10.4%, P = 0.002), with persistent significant differences in both hypoactive and mixed-type delirium between the groups ( P < 0.001 in all cases) (Table 3 ). Table 3 Primary and secondary outcomes before and after propensity score matching ( PSM ) Characteristics Before PSM ( n = 2674 ) After PSM ( n = 2144 ) Mild pain (n = 1210) Moderate-severe pain (n = 1464) P Mild pain (n = 1072) Moderate-severe pain (n = 1072) P Primary outcomes, ( n %) Postoperative delirium 116(9.6%) 238(16.3%) < 0.001 112(10.4%) 161(15.0%) 0.002 Hypoactive delirium 103(8.5%) 165(13.6%) 0.018 103(8.5%) 164(13.6%) < 0.001 Hyperactive delirium 3(0.2%) 8(0.7%) 0.364 3(0.2%) 8(0.7%) 0.225 Mixed delirium 21(1.7%) 54(4.5%) 0.002 21(1.7%) 54(4.5%) < 0.001 Secondary outcomes, ( n %) Postoperative anxiety 336(27.8%) 410(28.0%) 0.892 295(27.5%) 290(27.0%) 0.808 Mild anxiety 205(16.9%) 267(18.2%) 0.366 182(17.0%) 183(17.1%) 0.954 Moderate anxiety 96(7.9%) 110(7.5%) 0.685 78(7.3%) 86(8.0%) 0.516 Severe anxiety 35(2.9%) 33(2.3%) 0.297 35(3.3%) 21(2.0%) 0.058 Postoperative depression 247(20.4%) 389(26.6%) < 0.001 224(20.9%) 290(27.0%) 0.001 Mild depression 138(11.4%) 200(13.7%) 0.081 127(11.8%) 139(13.0%) 0.432 Moderate depression 78(6.4%) 132(9.0%) 0.014 67(6.2%) 109(10.2%) 0.001 Moderate-severe depression 31(2.6%) 57(3.9%) 0.055 30(2.8%) 42(3.9%) 0.150 STROBE Statement—Checklist of items that should be included in reports of cohort studies Regarding secondary outcomes, before matching, the moderate-to-severe pain group showed a higher incidence of depressive symptoms (26.6 vs. 20.4%, P < 0.001), with the most pronounced difference in moderate depressive symptoms (9.0 vs. 6.4%, P = 0.014). After matching, significant differences persisted in overall depressive symptoms (27.0 vs. 20.9%, P = 0.001) and moderate depressive symptoms (10.2 vs. 6.2%, P = 0.001). However, no significant association was found between early postoperative acute pain and the incidence of overall postoperative anxiety symptoms or different anxiety levels, either before or after matching (Table 3 ). Results of the multivariate logistic regression for secondary outcomes are presented in Supplementary Table 3. We performed subgroup analyses in 2,674 elderly patients undergoing abdominal surgery, stratified by age, ASA classification, comorbidities, intra-operative dexmedetomidine, preoperative albumin levels, and operative duration. Significant associations between moderate-to-severe acute postoperative pain and delirium were observed in the following subgroups: ASA classification, comorbidity, intra-operative dexmedetomidine use, age < 75 years, albumin ≥ 35 g/L, and operative duration < 180 minutes (Fig. 2 ). Discussion This secondary analysis of multicenter prospective data included 2,674 elderly patients undergoing elective abdominal surgery. Key findings include that the incidence of moderate-to-severe pain during POD 7 was 54.7%, with this group demonstrating a significantly higher incidence of delirium than the mild pain group. Univariate analysis, multifactorial logistic regression, and PSM analyses consistently demonstrated a significant association between moderate-to-severe acute postoperative pain and the development of delirium as well as postoperative depressive states, but no significant link with postoperative anxiety states. Both before and after PSM, moderate-to-severe acute postoperative pain showed significant associations with hypoactive delirium, mixed-type delirium, and moderate postoperative depression. The incidence of delirium varied significantly among elderly patients, which may be attributed to the surgical type. Available research data indicate substantial heterogeneity of delirium risk across different surgical procedures. Delirium incidence was highest in cardiac surgery patients (26%) [ 13 ] , followed by vascular surgery (19.1%) [ 14 ] , arthroplasty (16.5%) [ 15 ] , and lowest in non-cardiac surgical patients (11.6%) [ 16 ] .Regarding specifically abdominal surgery, a prospective observational study of 184 thoracic and abdominal surgery cases reported a delirium incidence of 14.6% [ 17 ] . This finding aligns closely with the overall delirium incidence observed in this study (13.2%) among elderly patients undergoing abdominal surgery. The occurrence of delirium is influenced by multiple factors, with the risk significantly associated with patient-specific characteristics. A meta-analysis encompassing 21 studies found that age, BMI, ASA classification, comorbidities, and preoperative C-reactive protein levels were strongly correlated with delirium risk [ 18 ] . In addition to patient-related factors, intra-operative variables also contribute to delirium development. In a prospective cohort of geriatric patients undergoing major abdominal procedures, open laparotomy, intra-operative transfusion, and a diagnosis of colorectal cancer were independently associated with an increased incidence of postoperative delirium [ 19 ] . Clinical studies have further supported a link between postoperative pain and delirium. Prospective cohort data revealed that postoperative pain occurrence and intensity were independent predictors of delirium following major non-cardiac procedures in patients aged > 50 years [ 20 ] . Similarly, studies have demonstrated that postoperative pain increases the risk of delirium in geriatric patients following hip fracture or arthroplasty [ 21 , 22 ] . At the basic research level, animal experiments revealed that persistent acute pain after abdominal surgery exhibited a dose-dependent relationship with neurobehavioral changes associated with delirium [ 23 ] . The present study aligns with these findings, confirming a significant correlation between moderate-to-severe acute postoperative pain and delirium development in elderly patients undergoing elective abdominal surgery. In spite of these known risk associations, the incidence of acute postoperative pain remains high. Available data show that even in less invasive ambulatory surgeries, the incidence of moderate-to-severe pain within 24 hours post-surgery remains as high as 30% [ 24 ] . By contrast, the incidence of acute postoperative pain in comprehensive surgery was 48% [ 25 ] ,while for patients undergoing abdominal surgery, it reached 45.6% [ 26 ] .A 2016 cross-sectional observational study by British scholars, involving over 15,000 surgical patients, revealed that the prevalence of moderate postoperative pain in non-obstetric surgeries was 37.2%, with severe pain occurring in 11.0% of cases [ 27 ] . In the Chinese population, the prevalence of moderate-to-severe postoperative pain was 48.7%, with the incidence of acute postoperative pain following abdominal surgery exceeding 50% [ 28 ] . Notably, inadequate analgesic measures not only directly impede patient recovery but may also be a significant predisposing factor for delirium. The mechanism by which postoperative pain contributes to delirium involves a complex pathophysiological process with multiple interacting factors and pathways. Surgical trauma-induced tissue damage activates the innate immune system, triggering the release of pro-inflammatory cytokines (e.g., IL-1β, IL-6, ahd TNF-α). These inflammatory mediators not only enhance peripheral and central sensitization, leading to nociceptive hypersensitivity, but also impair cognitive function by disrupting the blood-brain barrier and altering neurotransmitter homeostasis. Additionally, pain may activate the hypothalamic-pituitary-adrenal (HPA) axis, stimulating increased glucocorticoid secretion 29 . Prolonged elevation of cortisol levels can cause hippocampal neuronal damage, negatively affecting memory and cognitive functions. Pain also disrupts neurotransmitter systems, promoting delirium by interfering with the normal metabolism of acetylcholine, dopamine, and serotonin. 30 Furthermore, painful stimuli increase the production of reactive oxygen species (ROS) in the hippocampus, leading to oxidative neuronal damage, which also increases the risk of delirium. 31,32 Peri-operative anxiety and depression are common negative emotional states associated with poor clinical outcomes. Elderly patients frequently experience mood disorders such as anxiety and depression postoperatively. Existing studies demonstrate a bidirectional relationship between negative emotions and acute pain, as depression and anxiety lower pain thresholds and amplify pain perception, while persistent nociceptive stimuli exacerbate mood disorders, creating a vicious cycle. 33 The multivariate analysis of secondary outcomes in this study revealed a significant association between moderate-to-severe acute postoperative pain and the onset of depressive symptoms. Analysis of Taiwan’s National Health Insurance Research Database (N = 141,466) identified chronic postsurgical pain as an independent predictor of postoperative depressive symptoms in patients aged > 20 years undergoing major surgery. 34 Further supporting this correlation, a multicenter prospective cohort study reported that patients with severe acute postpartum pain faced a threefold higher risk of postnatal depression compared to those with mild pain. 35 Our results corroborate these observations, confirming that moderate-to-severe acute postoperative pain is significantly correlated with subsequent depressive states. Several studies have demonstrated that peri-operative dexmedetomidine significantly reduces the incidence of delirium in elderly patients undergoing noncardiac surgery. 36,37 However, our subgroup analysis revealed a significant association between acute postoperative pain and delirium occurrence, regardless of dexmedetomidine use. This suggests that pain may contribute to delirium development through pathways independent of dexmedetomidine’s mechanism of action, highlighting the need for a multimodal peri-operative management strategy-incorporating both delirium-preventing medications (e.g., dexmedetomidine) and optimized pain control. Notably, our subgroup analysis indicated that the association between early postoperative moderate-to-severe pain and delirium risk was absent in specific subpopulations, including patients aged ≥ 75 years, those with albumin < 35g/L, and those with surgical duration ≥ 180 minutes. This observation underscores population heterogeneity in delirium pathogenesis. In patients with severely compromised physiological reserve, the impact of early postoperative pain on delirium may be overshadowed by stronger risk factors. However, this does not imply that pain management should be neglected; rather, comprehensive brain protection strategies should be tailored to the patient’s overall condition. Further studies are needed to elucidate the mechanisms underlying these subgroup differences using larger sample sizes or biomarker stratification (e.g., inflammatory factors, EEG). At the same time, patients with greater physiological reserve may experience excessive neural stimulation from uncontrolled pain, suggesting that even patients deemed low-risk who are undergoing minor procedures require individualized analgesic strategies. In spite of its valuable findings, our study has several limitations. Firstly, while we employed robust statistical methods including PSM and univariate or multivariate logistic regression to control for confounding factors, potential residual confounders, including unmeasured or unforeseen variables, may affect the pain-delirium association. Secondly, the lack of ward analgesia documentation (including opioid or non-opioid use) constitutes a major limitation, potentially introducing unmeasured confounding. Thirdly, our stringent exclusion criteria (e.g., preexisting psychiatric disorders, cognitive impairment, or postoperative ICU admission) may have excluded high-risk populations, potentially limiting the generalizability of our findings to broader surgical cohorts. These limitations highlight the need for future randomized controlled trials to establish causal relationships, refine pain management protocols, and identify surgery-specific biomarkers to facilitate personalized intervention strategies. Conclusions In our cohort of elderly patients undergoing elective abdominal surgery, moderate-to-severe acute pain on POD1 was significantly associated with both the development of delirium and depressive symptom during POD 7. These findings highlight the need to optimize postoperative analgesia to mitigate neuropsychiatric complications in geriatric surgical populations. Future randomized controlled trials should investigate targeted pain management strategies to reduce the incidence of delirium in this vulnerable population. Declarations Acknowledgements We are grateful to all the anesthesiology staff of the participating hospitals for clinical data collection . Author contributions Conceptualization: Li Tong, Yan-hong Liu and Hai-yue Ma; Methodology: Qiang Fu, Xin-yu Hao and Chen Zhang; Formal analysis and investigation: Hai-yue Ma, Xue-cai Lv, Zhuo-ning Zhang; Writing - original draft preparation: Hai-yue Ma, Xue-cai Lv, Chen Zhang; Writing - review and editing: Li Tong and Qiang Fu; Funding acquisition: Wei-dong Mi; Resources: Jiang-bei Cao; Supervision: Li Tong and Qiang Fu. All authors read and approved the final manuscript. Funding This work was supported by a grant from the National Key Research and Development Program of China (No.2018YFC2001901)and Beijing Natural Science Foundation (Grant No.7252015). Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Compliance with Ethical Standards Competing Interests The authors have no confict of interest to report, fnancial or otherwise. Ethical approval This secondary analysis of multicenter prospective data involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Clinical Research Ethics Committee of the First Medical Center of the Chinese PLA General Hospital approved this study (No.: S2025-137-02). Informed consen The need for individual informed consent was waived by the IRB due to the retrospective nature of this study. References Swarbrick CJ, Partridge JSL (2022) Evidence-based strategies to reduce the incidence of postoperative delirium: a narrative review. Anaesthesia 77(Suppl 1):92–101. https://doi.org/10.1111/anae.15607 Chen CC, Li HC, Liang JT et al (2017) Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial. JAMA Surg 152:827–834. https://doi.org/10.1001/jamasurg.2017.1083 Liu J, Li J, Wang J et al (2023) Associated factors for postoperative delirium following major abdominal surgery: A systematic review and meta-analysis. Int J Geriatr Psychiatry 38:e5942. https://doi.org/10.1002/gps.5942 Song YX, Wang Q, Ma YL et al (2024) Preoperative prognostic nutritional index predicts postoperative delirium in aged patients after surgery: A matched cohort study. Gen Hosp Psychiatry 86:58–66. https://doi.org/10.1016/j.genhospsych.2023.11.013 Li T, Li J, Yuan L et al (2022) Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial. JAMA 327:50–58. https://doi.org/10.1001/jama.2021.22647 Schnabel A, Yahiaoui-Doktor M, Meissner W et al (2020) Predicting poor postoperative acute pain outcome in adults: an international, multicentre database analysis of risk factors in 50,005 patients. Pain Rep 5:e831. https://doi.org/10.1097/PR9.0000000000000831 Iamaroon A, Wongviriyawong T, Sura-Arunsumrit P et al (2020) Incidence of and risk factors for postoperative delirium in older adult patients undergoing noncardiac surgery: a prospective study. BMC Geriatr 20:40. https://doi.org/10.1186/s12877-020-1449-8 Gerbershagen HJ, Rothaug J, Kalkman CJ et al (2011) Determination of moderate-to-severe postoperative pain on the numeric rating scale: a cut-off point analysis applying four different methods. Br J Anaesth 107:619–626. https://doi.org/10.1093/bja/aer195 Oberhaus J, Wang W, Mickle AM et al (2021) Evaluation of the 3-Minute Diagnostic Confusion Assessment Method for Identification of Postoperative Delirium in Older Patients. JAMA Netw Open 4:e2137267. https://doi.org/10.1001/jamanetworkopen.2021.37267 Kertz S, Bigda-Peyton J, Bjorgvinsson T (2013) Validity of the Generalized Anxiety Disorder-7 scale in an acute psychiatric sample. Clin Psychol Psychother 20:456–464. https://doi.org/10.1002/cpp.1802 Costantini L, Pasquarella C, Odone A et al (2020) Screening for depression in primary care with Patient Health Questionnaire-9 (PHQ-9): A systematic review. J Affect Disord 279:473–483. https://doi.org/10.1016/j.jad.2020.09.131 Lin YT, Lan KM, Wang LK et al (2016) Incidence, risk factors, and phenomenological characteristics of postoperative delirium in patients receiving intravenous patient-controlled analgesia: a prospective cohort study. Neuropsychiatr Dis Treat 12:3205–3212. https://doi.org/10.2147/NDT.S119817 Detroyer E, Dobbels F, Verfaillie E et al (2008) Is pre-operative anxiety and depression associated with onset of delirium after cardiac surgery in older patients? A prospective cohort study. J Am Geriatr Soc 56:2278–2284. https://doi.org/10.1111/j.1532-5415.2008.02013.x Galyfos GC, Geropapas GE, Sianou A et al (2017) Risk factors for postoperative delirium in patients undergoing vascular surgery. J Vasc Surg 66:937–946. https://doi.org/10.1016/j.jvs.2017.03.439 Chen W, Ke X, Wang X et al (2017) Prevalence and risk factors for postoperative delirium in total joint arthroplasty patients: A prospective study. Gen Hosp Psychiatry 46:55–61. https://doi.org/10.1016/j.genhosppsych.2017.03.008 Iamaroon A, Wongviriyawong T, Sura-Arunsumrit P et al (2020) Incidence of and risk factors for postoperative delirium in older adult patients undergoing noncardiac surgery: a prospective study. BMC Geriatr 20:40. https://doi.org/10.1186/s12877-020-1449-8 Liu J, Li J, He J et al (2022) The Age-adjusted Charlson Comorbidity Index predicts post-operative delirium in the elderly following thoracic and abdominal surgery: A prospective observational cohort study. Front Aging Neurosci 14:979119. https://doi.org/10.3389/fnagi.2022.979119 Sadeghirad B, Dodsworth BT, Schmutz Gelsomino N et al (2023) Peri-operative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis. JAMA Netw Open 6:e2337239. https://doi.org/10.1001/jamanetworkopen.2023.37239 Janssen TL, Steyerberg EW, Faes MC et al (2019) Risk factors for postoperative delirium after elective major abdominal surgery in elderly patients: A cohort study. Int J Surg 71:29–35. https://doi.org/10.1016/j.ijsu.2019.09.011 Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER (1998) The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 86(4):781–785. https://doi.org/10.1097/00000539-199804000-00019 Hao Y, Li W, Zheng M et al (2024) Effects of liposomal bupivacaine in pre-operative fascia iliac block on postoperative pain and delirium in elderly patients undergoing hip fracture surgery: a study protocol for a randomised, parallel controlled prospective clinical study. BMJ Open 14:e079067. https://doi.org/10.1136/bmjopen-2023-079067 Denny DL, Lindseth GN (2020) Pain, Opioid Intake, and Delirium Symptoms in Adults Following Joint Replacement Surgery. West J Nurs Res 42:165–176. https://doi.org/10.1177/0193945919849096 Koyama T, Kawano T, Iwata H, Aoyama B, Eguchi S, Nishigaki A, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Locatelli FM, Yokoyama M (2019) Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats. J Anesth 33(3):482–486. https://doi.org/10.1007/s00540-019-02635-3 McGrath B, Elgendy H, Chung F et al (2004) Thirty percent of patients have moderate to severe pain 24 hr after ambulatory surgery: a survey of 5,703 patients. Can J Anaesth 51:886–891. https://doi.org/10.1007/BF03018885 Hah JM, Cramer E, Hilmoe H et al (2019) Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open2 e190168. https://doi.org/10.1001/jamanetworkopen.2019.0168 Chen DX, Zhang YY, Liu J et al (2025) Postoperative acute pain trajectory and chronic postsurgical pain after abdominal surgery: a prospective cohort study and mediation analysis. Int J Surg 111:1968–1976. https://doi.org/10.1097/JS9.0000000000002218 Walker EMK, Bell M, Cook TM et al (2016) Patient reported outcome of adult peri-operative anaesthesia in the United Kingdom: a cross-sectional observational study. Br J Anaesth 117:758–766. https://doi.org/10.1016/j.lanwpc.2023.100822 Liu Y, Xiao S, Yang H et al (2023) Postoperative pain-related outcomes and peri-operative pain management in China: a population-based study. Lancet Reg Health West Pac 39:100822. https://doi.org/10.1016/j.lanwpc.2023.100822 Xie Z, Swain CA, Ward SA et al (2014) Preoperative cerebrospinal fluid β-Amyloid/Tau ratio and postoperative delirium. Ann Clin Transl Neurol 1:319–328. https://doi.org/10.1002/acn3.58 Ma JH, Liu YF, Hong H et al (2023) Effect of acute pain on the association between pre-operative cognitive impairment and postoperative delirium: a secondary analysis of three trials. Br J Anaesth 130:e272–e280. https://doi.org/10.1016/j.bja.2022.06.033 Liu Q, Sun YM, Huang H et al (2021) Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation. J Neuroinflammation 18:41. https://doi.org/10.1186/s12974-021-02089-z Wimmer GE, Büchel C (2021) Reactivation of Single-Episode Pain Patterns in the Hippocampus and Decision Making. J Neurosci 41:7894–7908. https://doi.org/10.1523/JNEUROSCI.1350-20.2021 Michaelides A, Zis P (2019) Depression, anxiety and acute pain: links and management challenges. Postgrad Med 131:438–444. https://doi.org/10.1080/00325481.2019.1663705 Sun M, Wang X, Lu Z et al (2025) Chronic postsurgical pain increases postoperative depression risk. J Epidemiol Commun Health 79(7):515–521. https://doi.org/10.1136/jech-2024-222761 Eisenach JC, Pan et al (2008) Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain 140:87–94. https://doi.org/10.1016/j.Pain.2008.07.011 Su X, Meng ZT et al (2016) Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 388:1893–1902. https://doi.org/10.1016/S0140-6736(16)30580-3 Qin C, Jiang Y, Lin C et al (2021) Perioperative dexmedetomidine administration to prevent delirium in adults after non-cardiac surgery: A systematic review and meta-analysis. J Clin Anesth 73:110308. https://doi.org/10.1016/j.jclinane.2021.110308 Supplementary Files STROBEStatement.docx SupplementalDigitalContent.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Minor revisions 19 Oct, 2025 Reviewers agreed at journal 15 Jul, 2025 Reviewers invited by journal 09 Jul, 2025 Editor assigned by journal 01 Jul, 2025 First submitted to journal 26 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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before and after matching between the mild pain and moderate-severe pain groups\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6987226/v1/f3acdaa9b015c68782eb657b.png"},{"id":86669560,"identity":"a5b8553a-d4a1-4dd2-9f78-08828324c40d","added_by":"auto","created_at":"2025-07-14 11:24:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":181262,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of the association between postoperative moderate-to-severe acute pain and POD, stratified by age, ASA classification, comorbidity, albumin levels, intra-operative dexmedetomidine use, and surgical duration\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6987226/v1/db4a848b8296650ed4679728.png"},{"id":86672467,"identity":"40ea0580-9c29-47b5-8a54-c4f8deab47fb","added_by":"auto","created_at":"2025-07-14 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11:24:15","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":35972,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalDigitalContent.docx","url":"https://assets-eu.researchsquare.com/files/rs-6987226/v1/006345a10844ab02b5e120c6.docx"}],"financialInterests":"","formattedTitle":"The effect of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery:a secondary analysis of multicenter prospective data","fulltext":[{"header":"Key Summary Points","content":"\u003cp\u003e\u003cstrong\u003eAim:\u003c/strong\u003eThis study aimed to investigate the impact of moderate-to-severe acute pain on postoperative day 1 (POD1) on delirium in elderly patients undergoing abdominal surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings:\u0026nbsp;\u003c/strong\u003eIn elderly patients undergoing elective abdominal surgery, moderate-to-severe pain on POD 1 was significantly associated with both delirium and depressive symptoms within 7 days of surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMessage:\u0026nbsp;\u003c/strong\u003eAdequate management of early postoperative acute pain may help prevent postoperative delirium in elderly patients.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eDelirium, a prevalent and severe postoperative complication in elderly patients, is clinically characterized by attention deficits, impaired consciousness, and disturbances in orientation, memory, and perception\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The incidence of delirium following non-cardiac surgeries ranges from 13 to 50%\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, with abdominal surgery specifically associated with a 21% incidence rate\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Delirium leads to multiple adverse outcomes including prolonged hospitalization, diminished quality of life, persistent cognitive decline, increased postoperative morbidity, elevated healthcare expenditures, and higher risk of mortality\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Furthermore, postoperative negative emotional states such as anxiety and depression frequently occur in elderly surgical patients, significantly compromising clinical outcomes.\u003c/p\u003e\u003cp\u003ePostoperative pain management remains a significant clinical challenge despite advancements in surgical and anesthetic techniques. The incidence of moderate-to-severe acute postoperative pain persists at elevated levels, with studies reporting rates reaching 50% in some populations\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. This is particularly concerning given the established association between pain and delirium in elderly surgical patients - a combination that frequently leads to adverse outcomes in the absence of timely prevention, diagnosis, and intervention. There is also emerging evidence of interconnections between pain, anxiety, and depression. Early postoperative acute pain is a modifiable and clinically significant indicator. Effective pain management strategies may therefore serve as preventive measures against delirium, anxiety, and depression in geriatric surgical patients.\u003c/p\u003e\u003cp\u003eConsequently, investigating the impact of early acute postoperative pain on delirium development and postoperative anxiety or depression symptoms holds significant clinical importance for optimizing peri-operative analgesia protocols and enhancing clinical outcomes in elderly surgical patients. This study will provide critical theoretical foundations for further optimizing comprehensive postoperative management protocols for elderly patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and cohort\u003c/h2\u003e\u003cp\u003eThis multicenter secondary analysis of prospective data included elderly patients who underwent elective abdominal surgery between April 2020 and April 2022 across five provinces or municipalities in China (Guizhou, Nanjing, Hunan, Hubei, and Beijing). Clinical data were systematically collected for analysis.\u003c/p\u003e\u003cp\u003eThe inclusion criteria were as follows: age\u0026thinsp;\u0026ge;\u0026thinsp;65 years; absence of auditory, visual, or cognitive impairments (operationally defined as a Chinese version of the Mini-Mental State Examination [MMSE] score\u0026thinsp;\u0026le;\u0026thinsp;17); scheduled for elective abdominal surgery under general anesthesia with endotracheal intubation; complete assessments for postoperative delirium, anxiety, and depression. Patients were excluded if they met any of the following criteria: history of severe psychiatric disorders or chronic use of psychotropic medications (n\u0026thinsp;=\u0026thinsp;715) ;NOTES: natural orifice transluminal endoscopic surgery (n\u0026thinsp;=\u0026thinsp;454); vascular interventional procedures (n\u0026thinsp;=\u0026thinsp;44); postoperative transfer to the intensive care unit (ICU) or death within 7 days after surgery (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eWe collected baseline characteristics and demographic data of the patients, including clinical information in the following areas: (1) Baseline characteristics: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status score, smoking, alcohol consumption, preoperative history of chronic pain, and comorbidities (hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, hepatic insufficiency, and renal insufficiency). (2) Pre-operative laboratory tests (the most recent prior to surgery): haemoglobin(Hb), white blood cell count, serum albumin. (3) Preoperative psychological assessments: anxiety and depression state evaluations. (4) Intra-operative variables: grade of operation, type of surgery, duration of surgery, transfusion, blood loss, intra-operative dexmedetomidine and nonsteroidal anti-inflammatory drugs (NSAIDs), drain, and patient-controlled intravenous analgesia (PCIA).\u003c/p\u003e\n\u003ch3\u003eSample size\u003c/h3\u003e\n\u003cp\u003eStatistical analyses were performed using PASS version 15.0. Based on an anticipated 4.7% intergroup difference in delirium incidence, with a two-sided α level of 0.05 and 80% power (β\u0026thinsp;=\u0026thinsp;0.20), our preliminary sample size calculation indicated a minimum requirement of 733 patients per group\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The final cohort of 2,674 patients included in our study clearly exceeded this minimal threshold, ensuring adequate statistical power.\u003c/p\u003e\n\u003ch3\u003eExposure\u003c/h3\u003e\n\u003cp\u003eIn this study, we defined the presence or absence of moderate-to-severe pain on POD1 as the exposure variable, assessed using the numerical rating scale (NRS) \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. An NRS score\u0026thinsp;\u0026lt;\u0026thinsp;4 on POD1 was classified as mild pain, while a score\u0026thinsp;\u0026ge;\u0026thinsp;4 indicated moderate-to-severe pain. Based on this exposure variable, patients were stratified into the mild pain group (NRS\u0026thinsp;\u0026lt;\u0026thinsp;4) and moderate-to-severe pain group (NRS\u0026thinsp;\u0026ge;\u0026thinsp;4).\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcomes were the incidence of delirium and its subtypes during POD 7. Delirium was assessed by trained staff using the 3D-CAM scale at bedside\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Assessments were conducted twice daily (in the morning and afternoon) throughout the postoperative period.\u003c/p\u003e\u003cp\u003eThe secondary outcomes included the incidence and subtypes of anxiety or depression symptoms. Trained assessors evaluated postoperative anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, administered at the patient's bedside during the recovery period\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. A score\u0026thinsp;\u0026gt;\u0026thinsp;5 was defined as indicating anxiety symptoms, with scores of 5\u0026ndash;8 indicating mild symptoms, 9\u0026ndash;14 representing moderate anxiety, and 15\u0026ndash;21 reflecting severe anxiety. Postoperative depressive symptoms were assessed by trained researchers using the validated Chinese version of the Patient Health Questionnaire-9 (PHQ-9) at the patient's bedside\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. A score\u0026thinsp;\u0026gt;\u0026thinsp;5 was defined as indicating depressive symptoms, with scores of 5\u0026ndash;9 representing mild symptoms and 10\u0026ndash;14 indicating moderate depression. A score of 15\u0026ndash;27 was classified as moderate-to-severe depression. These psychological assessments were conducted once during the postoperative hospitalization period, scheduled between postoperative days 3\u0026ndash;7.\u003c/p\u003e\u003cp\u003eFor patients discharged before completing all assessments (delirium, anxiety, or depression), trained researchers performed standardized telephone follow-up evaluations using the same assessment protocols.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eWe descriptively summarized patient characteristics stratified by the presence or absence of moderate-to-severe pain. Continuous variables were reported as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for normally distributed data or median (interquartile range) for non-normally distributed data, with between-group comparisons performed using Student's \u003cem\u003et\u003c/em\u003e-test or the Mann-Whitney U test, respectively. Categorical variables were summarized as frequencies (percentages) and analyzed using Pearson's chi-squared test.\u003c/p\u003e\u003cp\u003eUnivariate and multivariate regression analyses were performed to examine the relationship between acute pain and the incidence of early delirium. In the multivariate logistic regression model, a forced-entry method was applied, incorporating all predefined covariates. Variable selection for adjustment was guided by univariate screening and clinical plausibility regarding their association with delirium. To enhance the robustness of our findings, we performed PSM followed by subgroup analyses\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. We adjusted for covariates exhibiting a standardized mean difference (SMD)\u0026thinsp;\u0026gt;\u0026thinsp;0.2 between the mild and moderate-to-severe pain cohorts.Both the exposed and unexposed groups comprised 1,072 participants each. Post-matching balance was confirmed by achieving an SMD\u0026thinsp;\u0026lt;\u0026thinsp;0.2 for all included variables, indicating well-balanced baseline characteristics. Statistical significance was defined as a two-sided \u003cem\u003eP\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using the R software (version 4.0.1; R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe initially enrolled 3,389 patients aged 65 years or older. After excluding 715 patients based on the listed criteria, 2,674 were ultimately included in the analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median age was 70 years (interquartile range [IQR]: 67\u0026ndash;74), and 627 (23.4%) patients were aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years. Notably, the patients (1,779; 66.5%) were male. The overall incidence rate of delirium in this cohort was 13.2%. Patients were stratified into mild pain and moderate-to-severe pain groups. Significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were observed between the groups in terms of ASA classification, surgical type, operative duration, drain, intra-operative dexmedetomidine, NSAIDs, and PCIA. Other variables showed no statistical differences. Compared with the mild pain group, a higher percentage of patients in the moderate-to-severe pain group had lower ASA classification, smoked, consumed alcohol, had low hemoglobin, preoperative anxiety, preoperative depression, open surgeries, prolonged operative time, drain, non-use of dexmedetomidine, NSAIDs, and PCIA (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003eCharacteristics of the primary cohort before and after matching\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM (n\u0026thinsp;=\u0026thinsp;2674)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e\u003cp\u003eAfter PSM (n\u0026thinsp;=\u0026thinsp;2144)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMild pain(n\u0026thinsp;=\u0026thinsp;1210)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eModerate-severe pain (n\u0026thinsp;=\u0026thinsp;1464)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMild pain(n\u0026thinsp;=\u0026thinsp;1072)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eModerate-severe pain (n\u0026thinsp;=\u0026thinsp;1072)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative variables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (median [interquartile range]), yr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70.00 [67.00 to 74.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71.00 [67.00 to 74.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.00 [67.00 to 74.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.486\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e71.00 [68.00 to 74.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e70.00 [67.00 to 74.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1779 (66.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e808 (66.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e971 (66.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.805\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e696 (64.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e724 (67.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.201\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (median [interquartile range]), kg/m\u0026sup2;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.10 [22.08 to 25.68]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.10 [22.25 to 25.67]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.03 [21.97 to 25.68]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.060\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24.10 [22.29 to 25.77]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e24.10 [22.04 to 25.61]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.048\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA*, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.225\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅠ/Ⅱ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1899 (71.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e795 (65.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1104 (75.4)\u003c/p\u003e\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\u003cp\u003e768 (71.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e768 (71.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢ/Ⅴ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e775 (29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e415 (34.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e360 (24.6)\u003c/p\u003e\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\u003cp\u003e304 (28.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e304 (28.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidity, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.560\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.023\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.960\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2034 (76.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e914 (75.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1120 (76.5)\u003c/p\u003e\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\u003cp\u003e816 (76.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e817 (76.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e640 (23.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e296 (24.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e344 (23.5)\u003c/p\u003e\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\u003cp\u003e256 (23.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e255 (23.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoke, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e745 (27.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e306 (25.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e439 (29.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e274 (25.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e332 (31.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.117\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e710 (26.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e297 (24.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e413 (28.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e271 (25.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e309 (28.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative chronic pain, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e88 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40 (2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e44 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22 (2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.145\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative evaluation with scales\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative anxiety, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1025 (38.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e452 (37.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e573 (39.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e392 (36.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e427 (39.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative depression, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e775 (29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e330 (27.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e445 (30.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e289 (27.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e330 (30.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative laboratory examinations\u003c/b\u003e\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHaemoglobin, g dl-1, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.092\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.043\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;13.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1470 (55.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e635 (52.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e835 (57.0)\u003c/p\u003e\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\u003cp\u003e575 (53.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e598 (55.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;13.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1204 (45.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e575 (47.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e629 (43.0)\u003c/p\u003e\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\u003cp\u003e497 (46.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e474 (44.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (median [interquartile range]), g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.70 [37.10 to 41.90]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.70 [37.20 to 41.80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39.70 [37.00 to 42.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.960\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e39.90 [37.30 to 41.92]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e40.00 [37.20 to 42.10]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.517\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC count(median [interquartile range]), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.73 [4.68 to 6.79]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.73 [4.64 to 6.80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.74 [4.71 to 6.77]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.778\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.70 [4.61 to 6.72]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.78 [4.69 to 6.80]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.354\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical/Anesthetic parameters\u003c/b\u003e\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade of operation, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.027\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.965\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1020 (38.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e453 (37.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e567 (38.7)\u003c/p\u003e\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\u003cp\u003e429 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e428 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1654 (61.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e757 (62.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e897 (61.3)\u003c/p\u003e\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\u003cp\u003e643 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e644 (60.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of surgical*, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.221\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.043\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMinimally invasive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2210 (82.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1060 (87.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1150 (78.6)\u003c/p\u003e\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\u003cp\u003e922 (86.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e953 (89.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOpen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e464 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e314 (21.4)\u003c/p\u003e\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\u003cp\u003e150 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e119 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of surgery,min, \u003cem\u003en\u003c/em\u003e (%)\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=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.114\u003c/p\u003e\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=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1439 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e689 (57.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e750 (51.2)\u003c/p\u003e\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\u003cp\u003e618 (57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e575 (53.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1235 (46.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e521 (43.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e714 (48.8)\u003c/p\u003e\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\u003cp\u003e454 (42.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e497 (46.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood loss (median [interquartile range]), ml\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100.00 [50.00 to 116.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.00 [50.00 to 116.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100.00 [50.00 to 116.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.555\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e100.00 [30.00 to 116.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e100.00 [50.00 to 116.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.387\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood transfusion, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e240 (8.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e117 (9.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e123 (8.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.256\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e103 (9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e103 (9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntraoperative medication\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDexmedetomidine*, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e659 (24.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e355 (29.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e304 (20.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e244 (22.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e225 (21.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.321\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNSAIDs, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1420 (53.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e609 (50.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e811 (55.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e567 (52.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e581 (54.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.544\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.026\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCIA*, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1326 (49.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e498 (41.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e828 (56.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.311\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e498 (46.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e533 (49.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrain, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2292 (85.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1011 (83.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1281 (87.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e887 (82.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e918 (85.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eThe data are shown as the median [interquartile range], \u003cem\u003en\u003c/em\u003e (%).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eAbbreviations: SMD, standardized mean difference; PSM, propensity score matching; BMI, body mass index; ASA, American Society of Anesthesiologists Physical status classification system; WBC, white blood cell; NSAIDs, non-steroidal anti-inflammatory drugs; PCIA, patient - controlled intravenous analgesia.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003e*Variables included in the Propensity score.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWe used four logistic regression models to analyze the association between moderate-to-severe acute postoperative pain and delirium on POD 1 in elderly patients. In the univariate analysis, moderate-to-severe acute pain was significantly associated with an increased risk of delirium (OR\u0026thinsp;=\u0026thinsp;1.831, 95% CI: 1.445 to 2.319, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The univariate logistic regression results are presented in Supplementary Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003eIn all multivariable regression models, moderate-to-severe acute pain remained an independent risk factor for delirium: Model Ⅱ OR\u0026thinsp;=\u0026thinsp;1.823 (95% CI: 1.434 to 2.317, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); Model Ⅲ OR\u0026thinsp;=\u0026thinsp;1.613 (95% CI: 1.266 to 2.055, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); Model Ⅳ OR\u0026thinsp;=\u0026thinsp;1.629 (95% CI: 1.274 to 2.084, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); Model PSM OR\u0026thinsp;=\u0026thinsp;1.443 (95% CI: 1.108 to 1.879, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The detailed specifications of each model are provided in Supplementary Table\u0026nbsp;2.\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\u003eAssociation between postoperative day 1: moderate-severe acute pain and delirium with logistic regression models and propensity score matching ( PSM ) analysis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel 1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.831\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.445\u0026ndash;2.319\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.823\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.434\u0026ndash;2.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.613\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.266\u0026ndash;2.055\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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 4\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.629\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.274\u0026ndash;2.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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 PSM (n\u0026thinsp;=\u0026thinsp;2144)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.108\u0026ndash;1.879\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\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=\"4\"\u003ea Model 1 a univariate logistic regression analysis.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eb Model 2 adjusted for age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status score, smoking, alcohol consumption, preoperative history of chronic pain, and comorbidity, hemoglobin (Hb), white blood cell count, serum albumin,preoperative psychological assessments: anxiety and depression state evaluations.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003ec Model 3 adjusted for grade of operation, type of surgery, duration of surgery, transfusion, blood loss, intraoperative dexmedetomidine, nonsteroidal anti-inflammatory drugs (NSAIDs), drain, patient-controlled intravenous analgesia (PCIA).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003ed Model 4 adjusted for model 2 plus model 3.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003ee Model PSM a multivariable logistic regression.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePSM was performed at a 1:1 ratio to balance the baseline covariates. Variables with an SMD\u0026thinsp;\u0026gt;\u0026thinsp;0.2 (ASA classification, surgical type, intra-operative dexmedetomidine, PCIA) were matched between the mild and moderate-to-severe pain groups. Kernel density plots illustrated the propensity score (PS) distributions before and after matching (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Post-matching, each group comprised 1,072 patients, with all baseline characteristics balanced (SMD\u0026thinsp;\u0026lt;\u0026thinsp;0.2; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWithin the first 7 postoperative days, the incidence of delirium was significantly higher in the moderate-to-severe pain group compared to the mild pain group (16.3 vs. 9.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Among delirium subtypes, significant differences were observed in hypoactive delirium (13.6 vs. 8.5%) and mixed-type delirium (4.5 vs. 1.7%). After 1:1 PSM (n\u0026thinsp;=\u0026thinsp;2,144), the association between moderate-to-severe pain and delirium remained significant (15.0 vs. 10.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), with persistent significant differences in both hypoactive and mixed-type delirium between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 in all cases) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003ePrimary and secondary outcomes before and after propensity score matching ( PSM )\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eBefore PSM ( n\u0026thinsp;=\u0026thinsp;2674 )\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eAfter PSM ( n\u0026thinsp;=\u0026thinsp;2144 )\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMild pain (n\u0026thinsp;=\u0026thinsp;1210)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModerate-severe pain (n\u0026thinsp;=\u0026thinsp;1464)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMild pain (n\u0026thinsp;=\u0026thinsp;1072)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eModerate-severe pain (n\u0026thinsp;=\u0026thinsp;1072)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary outcomes, (\u003cem\u003en\u003c/em\u003e%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative delirium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e116(9.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e238(16.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e112(10.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e161(15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypoactive delirium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e103(8.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e165(13.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e103(8.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e164(13.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\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\u003eHyperactive delirium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3(0.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8(0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.364\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3(0.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8(0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMixed delirium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21(1.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21(1.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e54(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\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\u003e\u003cb\u003eSecondary outcomes, (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u003cb\u003e%)\u003c/b\u003e\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative anxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e336(27.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e410(28.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.892\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e295(27.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e290(27.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.808\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMild anxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e205(16.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e267(18.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.366\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e182(17.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e183(17.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.954\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate anxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e96(7.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e110(7.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.685\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e78(7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e86(8.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.516\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere anxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35(2.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33(2.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e35(3.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e21(2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.058\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e247(20.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e389(26.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e224(20.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e290(27.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMild depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e138(11.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e200(13.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e127(11.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e139(13.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.432\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e78(6.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e132(9.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e67(6.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e109(10.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate-severe depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e31(2.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57(3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.055\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e30(2.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e42(3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.150\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eSTROBE Statement\u0026mdash;Checklist of items that should be included in reports of \u003cb\u003ecohort studies\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRegarding secondary outcomes, before matching, the moderate-to-severe pain group showed a higher incidence of depressive symptoms (26.6 vs. 20.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with the most pronounced difference in moderate depressive symptoms (9.0 vs. 6.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014). After matching, significant differences persisted in overall depressive symptoms (27.0 vs. 20.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and moderate depressive symptoms (10.2 vs. 6.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). However, no significant association was found between early postoperative acute pain and the incidence of overall postoperative anxiety symptoms or different anxiety levels, either before or after matching (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Results of the multivariate logistic regression for secondary outcomes are presented in Supplementary Table\u0026nbsp;3.\u003c/p\u003e\u003cp\u003eWe performed subgroup analyses in 2,674 elderly patients undergoing abdominal surgery, stratified by age, ASA classification, comorbidities, intra-operative dexmedetomidine, preoperative albumin levels, and operative duration. Significant associations between moderate-to-severe acute postoperative pain and delirium were observed in the following subgroups: ASA classification, comorbidity, intra-operative dexmedetomidine use, age\u0026thinsp;\u0026lt;\u0026thinsp;75 years, albumin\u0026thinsp;\u0026ge;\u0026thinsp;35 g/L, and operative duration\u0026thinsp;\u0026lt;\u0026thinsp;180 minutes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis secondary analysis of multicenter prospective data included 2,674 elderly patients undergoing elective abdominal surgery. Key findings include that the incidence of moderate-to-severe pain during POD 7 was 54.7%, with this group demonstrating a significantly higher incidence of delirium than the mild pain group. Univariate analysis, multifactorial logistic regression, and PSM analyses consistently demonstrated a significant association between moderate-to-severe acute postoperative pain and the development of delirium as well as postoperative depressive states, but no significant link with postoperative anxiety states. Both before and after PSM, moderate-to-severe acute postoperative pain showed significant associations with hypoactive delirium, mixed-type delirium, and moderate postoperative depression.\u003c/p\u003e\u003cp\u003eThe incidence of delirium varied significantly among elderly patients, which may be attributed to the surgical type. Available research data indicate substantial heterogeneity of delirium risk across different surgical procedures. Delirium incidence was highest in cardiac surgery patients (26%)\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, followed by vascular surgery (19.1%)\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, arthroplasty (16.5%)\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, and lowest in non-cardiac surgical patients (11.6%)\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.Regarding specifically abdominal surgery, a prospective observational study of 184 thoracic and abdominal surgery cases reported a delirium incidence of 14.6%\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. This finding aligns closely with the overall delirium incidence observed in this study (13.2%) among elderly patients undergoing abdominal surgery.\u003c/p\u003e\u003cp\u003eThe occurrence of delirium is influenced by multiple factors, with the risk significantly associated with patient-specific characteristics. A meta-analysis encompassing 21 studies found that age, BMI, ASA classification, comorbidities, and preoperative C-reactive protein levels were strongly correlated with delirium risk\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. In addition to patient-related factors, intra-operative variables also contribute to delirium development. In a prospective cohort of geriatric patients undergoing major abdominal procedures, open laparotomy, intra-operative transfusion, and a diagnosis of colorectal cancer were independently associated with an increased incidence of postoperative delirium\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eClinical studies have further supported a link between postoperative pain and delirium. Prospective cohort data revealed that postoperative pain occurrence and intensity were independent predictors of delirium following major non-cardiac procedures in patients aged\u0026thinsp;\u0026gt;\u0026thinsp;50 years\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Similarly, studies have demonstrated that postoperative pain increases the risk of delirium in geriatric patients following hip fracture or arthroplasty\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. At the basic research level, animal experiments revealed that persistent acute pain after abdominal surgery exhibited a dose-dependent relationship with neurobehavioral changes associated with delirium\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. The present study aligns with these findings, confirming a significant correlation between moderate-to-severe acute postoperative pain and delirium development in elderly patients undergoing elective abdominal surgery.\u003c/p\u003e\u003cp\u003eIn spite of these known risk associations, the incidence of acute postoperative pain remains high. Available data show that even in less invasive ambulatory surgeries, the incidence of moderate-to-severe pain within 24 hours post-surgery remains as high as 30%\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. By contrast, the incidence of acute postoperative pain in comprehensive surgery was 48%\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e,while for patients undergoing abdominal surgery, it reached 45.6%\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.A 2016 cross-sectional observational study by British scholars, involving over 15,000 surgical patients, revealed that the prevalence of moderate postoperative pain in non-obstetric surgeries was 37.2%, with severe pain occurring in 11.0% of cases\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. In the Chinese population, the prevalence of moderate-to-severe postoperative pain was 48.7%, with the incidence of acute postoperative pain following abdominal surgery exceeding 50%\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Notably, inadequate analgesic measures not only directly impede patient recovery but may also be a significant predisposing factor for delirium.\u003c/p\u003e\u003cp\u003eThe mechanism by which postoperative pain contributes to delirium involves a complex pathophysiological process with multiple interacting factors and pathways. Surgical trauma-induced tissue damage activates the innate immune system, triggering the release of pro-inflammatory cytokines (e.g., IL-1β, IL-6, ahd TNF-α). These inflammatory mediators not only enhance peripheral and central sensitization, leading to nociceptive hypersensitivity, but also impair cognitive function by disrupting the blood-brain barrier and altering neurotransmitter homeostasis. Additionally, pain may activate the hypothalamic-pituitary-adrenal (HPA) axis, stimulating increased glucocorticoid secretion\u003csup\u003e29\u003c/sup\u003e. Prolonged elevation of cortisol levels can cause hippocampal neuronal damage, negatively affecting memory and cognitive functions. Pain also disrupts neurotransmitter systems, promoting delirium by interfering with the normal metabolism of acetylcholine, dopamine, and serotonin.\u003csup\u003e30\u003c/sup\u003e Furthermore, painful stimuli increase the production of reactive oxygen species (ROS) in the hippocampus, leading to oxidative neuronal damage, which also increases the risk of delirium.\u003csup\u003e31,32\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePeri-operative anxiety and depression are common negative emotional states associated with poor clinical outcomes. Elderly patients frequently experience mood disorders such as anxiety and depression postoperatively. Existing studies demonstrate a bidirectional relationship between negative emotions and acute pain, as depression and anxiety lower pain thresholds and amplify pain perception, while persistent nociceptive stimuli exacerbate mood disorders, creating a vicious cycle.\u003csup\u003e33\u003c/sup\u003eThe multivariate analysis of secondary outcomes in this study revealed a significant association between moderate-to-severe acute postoperative pain and the onset of depressive symptoms. Analysis of Taiwan\u0026rsquo;s National Health Insurance Research Database (N\u0026thinsp;=\u0026thinsp;141,466) identified chronic postsurgical pain as an independent predictor of postoperative depressive symptoms in patients aged\u0026thinsp;\u0026gt;\u0026thinsp;20 years undergoing major surgery.\u003csup\u003e34\u003c/sup\u003e Further supporting this correlation, a multicenter prospective cohort study reported that patients with severe acute postpartum pain faced a threefold higher risk of postnatal depression compared to those with mild pain.\u003csup\u003e35\u003c/sup\u003eOur results corroborate these observations, confirming that moderate-to-severe acute postoperative pain is significantly correlated with subsequent depressive states.\u003c/p\u003e\u003cp\u003eSeveral studies have demonstrated that peri-operative dexmedetomidine significantly reduces the incidence of delirium in elderly patients undergoing noncardiac surgery.\u003csup\u003e36,37\u003c/sup\u003eHowever, our subgroup analysis revealed a significant association between acute postoperative pain and delirium occurrence, regardless of dexmedetomidine use. This suggests that pain may contribute to delirium development through pathways independent of dexmedetomidine\u0026rsquo;s mechanism of action, highlighting the need for a multimodal peri-operative management strategy-incorporating both delirium-preventing medications (e.g., dexmedetomidine) and optimized pain control. Notably, our subgroup analysis indicated that the association between early postoperative moderate-to-severe pain and delirium risk was absent in specific subpopulations, including patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years, those with albumin\u0026thinsp;\u0026lt;\u0026thinsp;35g/L, and those with surgical duration\u0026thinsp;\u0026ge;\u0026thinsp;180 minutes. This observation underscores population heterogeneity in delirium pathogenesis. In patients with severely compromised physiological reserve, the impact of early postoperative pain on delirium may be overshadowed by stronger risk factors. However, this does not imply that pain management should be neglected; rather, comprehensive brain protection strategies should be tailored to the patient\u0026rsquo;s overall condition. Further studies are needed to elucidate the mechanisms underlying these subgroup differences using larger sample sizes or biomarker stratification (e.g., inflammatory factors, EEG). At the same time, patients with greater physiological reserve may experience excessive neural stimulation from uncontrolled pain, suggesting that even patients deemed low-risk who are undergoing minor procedures require individualized analgesic strategies.\u003c/p\u003e\u003cp\u003eIn spite of its valuable findings, our study has several limitations. Firstly, while we employed robust statistical methods including PSM and univariate or multivariate logistic regression to control for confounding factors, potential residual confounders, including unmeasured or unforeseen variables, may affect the pain-delirium association. Secondly, the lack of ward analgesia documentation (including opioid or non-opioid use) constitutes a major limitation, potentially introducing unmeasured confounding. Thirdly, our stringent exclusion criteria (e.g., preexisting psychiatric disorders, cognitive impairment, or postoperative ICU admission) may have excluded high-risk populations, potentially limiting the generalizability of our findings to broader surgical cohorts. These limitations highlight the need for future randomized controlled trials to establish causal relationships, refine pain management protocols, and identify surgery-specific biomarkers to facilitate personalized intervention strategies.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn our cohort of elderly patients undergoing elective abdominal surgery, moderate-to-severe acute pain on POD1 was significantly associated with both the development of delirium and depressive symptom during POD 7. These findings highlight the need to optimize postoperative analgesia to mitigate neuropsychiatric complications in geriatric surgical populations. Future randomized controlled trials should investigate targeted pain management strategies to reduce the incidence of delirium in this vulnerable population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe are grateful to all the anesthesiology staff of the participating hospitals for clinical data collection .\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConceptualization: Li Tong, Yan-hong Liu and Hai-yue Ma; Methodology: Qiang Fu, Xin-yu Hao and Chen Zhang; Formal analysis and investigation: Hai-yue Ma, Xue-cai Lv, Zhuo-ning Zhang; Writing - original draft preparation: Hai-yue Ma, Xue-cai Lv, Chen Zhang; Writing - review and editing: Li Tong and Qiang Fu; Funding acquisition: Wei-dong Mi; Resources: Jiang-bei Cao; Supervision: Li Tong and Qiang Fu. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis work was supported by a grant from the National Key Research and Development Program of China (No.2018YFC2001901)and Beijing Natural Science Foundation (Grant No.7252015).\u003c/p\u003e\n\u003cp\u003eData availability\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompliance with Ethical Standards\u003c/p\u003e\n\u003cp\u003eCompeting Interests\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors have no confict of interest to report, fnancial or otherwise.\u003c/p\u003e\n\u003cp\u003eEthical approval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis secondary analysis of multicenter prospective data involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Clinical Research Ethics Committee of the First Medical Center of the Chinese PLA General Hospital approved this study (No.: S2025-137-02).\u003c/p\u003e\n\u003cp\u003eInformed consen The need for individual informed consent was waived by the IRB due to the retrospective nature of this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSwarbrick CJ, Partridge JSL (2022) Evidence-based strategies to reduce the incidence of postoperative delirium: a narrative review. Anaesthesia 77(Suppl 1):92\u0026ndash;101. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/anae.15607\u003c/span\u003e\u003cspan address=\"10.1111/anae.15607\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen CC, Li HC, Liang JT et al (2017) Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial. JAMA Surg 152:827\u0026ndash;834. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamasurg.2017.1083\u003c/span\u003e\u003cspan address=\"10.1001/jamasurg.2017.1083\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J, Li J, Wang J et al (2023) Associated factors for postoperative delirium following major abdominal surgery: A systematic review and meta-analysis. Int J Geriatr Psychiatry 38:e5942. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/gps.5942\u003c/span\u003e\u003cspan address=\"10.1002/gps.5942\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong YX, Wang Q, Ma YL et al (2024) Preoperative prognostic nutritional index predicts postoperative delirium in aged patients after surgery: A matched cohort study. Gen Hosp Psychiatry 86:58\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.genhospsych.2023.11.013\u003c/span\u003e\u003cspan address=\"10.1016/j.genhospsych.2023.11.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi T, Li J, Yuan L et al (2022) Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial. JAMA 327:50\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jama.2021.22647\u003c/span\u003e\u003cspan address=\"10.1001/jama.2021.22647\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchnabel A, Yahiaoui-Doktor M, Meissner W et al (2020) Predicting poor postoperative acute pain outcome in adults: an international, multicentre database analysis of risk factors in 50,005 patients. Pain Rep 5:e831. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/PR9.0000000000000831\u003c/span\u003e\u003cspan address=\"10.1097/PR9.0000000000000831\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIamaroon A, Wongviriyawong T, Sura-Arunsumrit P et al (2020) Incidence of and risk factors for postoperative delirium in older adult patients undergoing noncardiac surgery: a prospective study. BMC Geriatr 20:40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12877-020-1449-8\u003c/span\u003e\u003cspan address=\"10.1186/s12877-020-1449-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGerbershagen HJ, Rothaug J, Kalkman CJ et al (2011) Determination of moderate-to-severe postoperative pain on the numeric rating scale: a cut-off point analysis applying four different methods. Br J Anaesth 107:619\u0026ndash;626. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/bja/aer195\u003c/span\u003e\u003cspan address=\"10.1093/bja/aer195\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOberhaus J, Wang W, Mickle AM et al (2021) Evaluation of the 3-Minute Diagnostic Confusion Assessment Method for Identification of Postoperative Delirium in Older Patients. JAMA Netw Open 4:e2137267. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamanetworkopen.2021.37267\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2021.37267\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKertz S, Bigda-Peyton J, Bjorgvinsson T (2013) Validity of the Generalized Anxiety Disorder-7 scale in an acute psychiatric sample. Clin Psychol Psychother 20:456\u0026ndash;464. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cpp.1802\u003c/span\u003e\u003cspan address=\"10.1002/cpp.1802\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCostantini L, Pasquarella C, Odone A et al (2020) Screening for depression in primary care with Patient Health Questionnaire-9 (PHQ-9): A systematic review. J Affect Disord 279:473\u0026ndash;483. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2020.09.131\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2020.09.131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin YT, Lan KM, Wang LK et al (2016) Incidence, risk factors, and phenomenological characteristics of postoperative delirium in patients receiving intravenous patient-controlled analgesia: a prospective cohort study. Neuropsychiatr Dis Treat 12:3205\u0026ndash;3212. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/NDT.S119817\u003c/span\u003e\u003cspan address=\"10.2147/NDT.S119817\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDetroyer E, Dobbels F, Verfaillie E et al (2008) Is pre-operative anxiety and depression associated with onset of delirium after cardiac surgery in older patients? A prospective cohort study. J Am Geriatr Soc 56:2278\u0026ndash;2284. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1532-5415.2008.02013.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1532-5415.2008.02013.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGalyfos GC, Geropapas GE, Sianou A et al (2017) Risk factors for postoperative delirium in patients undergoing vascular surgery. J Vasc Surg 66:937\u0026ndash;946. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jvs.2017.03.439\u003c/span\u003e\u003cspan address=\"10.1016/j.jvs.2017.03.439\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen W, Ke X, Wang X et al (2017) Prevalence and risk factors for postoperative delirium in total joint arthroplasty patients: A prospective study. Gen Hosp Psychiatry 46:55\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.genhosppsych.2017.03.008\u003c/span\u003e\u003cspan address=\"10.1016/j.genhosppsych.2017.03.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIamaroon A, Wongviriyawong T, Sura-Arunsumrit P et al (2020) Incidence of and risk factors for postoperative delirium in older adult patients undergoing noncardiac surgery: a prospective study. BMC Geriatr 20:40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12877-020-1449-8\u003c/span\u003e\u003cspan address=\"10.1186/s12877-020-1449-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J, Li J, He J et al (2022) The Age-adjusted Charlson Comorbidity Index predicts post-operative delirium in the elderly following thoracic and abdominal surgery: A prospective observational cohort study. Front Aging Neurosci 14:979119. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fnagi.2022.979119\u003c/span\u003e\u003cspan address=\"10.3389/fnagi.2022.979119\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSadeghirad B, Dodsworth BT, Schmutz Gelsomino N et al (2023) Peri-operative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis. JAMA Netw Open 6:e2337239. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamanetworkopen.2023.37239\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2023.37239\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJanssen TL, Steyerberg EW, Faes MC et al (2019) Risk factors for postoperative delirium after elective major abdominal surgery in elderly patients: A cohort study. Int J Surg 71:29\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijsu.2019.09.011\u003c/span\u003e\u003cspan address=\"10.1016/j.ijsu.2019.09.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER (1998) The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 86(4):781\u0026ndash;785. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/00000539-199804000-00019\u003c/span\u003e\u003cspan address=\"10.1097/00000539-199804000-00019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHao Y, Li W, Zheng M et al (2024) Effects of liposomal bupivacaine in pre-operative fascia iliac block on postoperative pain and delirium in elderly patients undergoing hip fracture surgery: a study protocol for a randomised, parallel controlled prospective clinical study. BMJ Open 14:e079067. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bmjopen-2023-079067\u003c/span\u003e\u003cspan address=\"10.1136/bmjopen-2023-079067\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDenny DL, Lindseth GN (2020) Pain, Opioid Intake, and Delirium Symptoms in Adults Following Joint Replacement Surgery. West J Nurs Res 42:165\u0026ndash;176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/0193945919849096\u003c/span\u003e\u003cspan address=\"10.1177/0193945919849096\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoyama T, Kawano T, Iwata H, Aoyama B, Eguchi S, Nishigaki A, Yamanaka D, Tateiwa H, Shigematsu-Locatelli M, Locatelli FM, Yokoyama M (2019) Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats. J Anesth 33(3):482\u0026ndash;486. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00540-019-02635-3\u003c/span\u003e\u003cspan address=\"10.1007/s00540-019-02635-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcGrath B, Elgendy H, Chung F et al (2004) Thirty percent of patients have moderate to severe pain 24 hr after ambulatory surgery: a survey of 5,703 patients. Can J Anaesth 51:886\u0026ndash;891. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/BF03018885\u003c/span\u003e\u003cspan address=\"10.1007/BF03018885\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHah JM, Cramer E, Hilmoe H et al (2019) Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open2 e190168. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamanetworkopen.2019.0168\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2019.0168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen DX, Zhang YY, Liu J et al (2025) Postoperative acute pain trajectory and chronic postsurgical pain after abdominal surgery: a prospective cohort study and mediation analysis. Int J Surg 111:1968\u0026ndash;1976. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/JS9.0000000000002218\u003c/span\u003e\u003cspan address=\"10.1097/JS9.0000000000002218\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWalker EMK, Bell M, Cook TM et al (2016) Patient reported outcome of adult peri-operative anaesthesia in the United Kingdom: a cross-sectional observational study. Br J Anaesth 117:758\u0026ndash;766. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.lanwpc.2023.100822\u003c/span\u003e\u003cspan address=\"10.1016/j.lanwpc.2023.100822\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Y, Xiao S, Yang H et al (2023) Postoperative pain-related outcomes and peri-operative pain management in China: a population-based study. Lancet Reg Health West Pac 39:100822. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.lanwpc.2023.100822\u003c/span\u003e\u003cspan address=\"10.1016/j.lanwpc.2023.100822\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXie Z, Swain CA, Ward SA et al (2014) Preoperative cerebrospinal fluid β-Amyloid/Tau ratio and postoperative delirium. Ann Clin Transl Neurol 1:319\u0026ndash;328. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/acn3.58\u003c/span\u003e\u003cspan address=\"10.1002/acn3.58\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMa JH, Liu YF, Hong H et al (2023) Effect of acute pain on the association between pre-operative cognitive impairment and postoperative delirium: a secondary analysis of three trials. Br J Anaesth 130:e272\u0026ndash;e280. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bja.2022.06.033\u003c/span\u003e\u003cspan address=\"10.1016/j.bja.2022.06.033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Q, Sun YM, Huang H et al (2021) Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation. J Neuroinflammation 18:41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12974-021-02089-z\u003c/span\u003e\u003cspan address=\"10.1186/s12974-021-02089-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWimmer GE, B\u0026uuml;chel C (2021) Reactivation of Single-Episode Pain Patterns in the Hippocampus and Decision Making. J Neurosci 41:7894\u0026ndash;7908. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1523/JNEUROSCI.1350-20.2021\u003c/span\u003e\u003cspan address=\"10.1523/JNEUROSCI.1350-20.2021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMichaelides A, Zis P (2019) Depression, anxiety and acute pain: links and management challenges. Postgrad Med 131:438\u0026ndash;444. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/00325481.2019.1663705\u003c/span\u003e\u003cspan address=\"10.1080/00325481.2019.1663705\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSun M, Wang X, Lu Z et al (2025) Chronic postsurgical pain increases postoperative depression risk. J Epidemiol Commun Health 79(7):515\u0026ndash;521. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/jech-2024-222761\u003c/span\u003e\u003cspan address=\"10.1136/jech-2024-222761\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEisenach JC, Pan et al (2008) Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain 140:87\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.Pain.2008.07.011\u003c/span\u003e\u003cspan address=\"10.1016/j.Pain.2008.07.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSu X, Meng ZT et al (2016) Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 388:1893\u0026ndash;1902. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(16)30580-3\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(16)30580-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQin C, Jiang Y, Lin C et al (2021) Perioperative dexmedetomidine administration to prevent delirium in adults after non-cardiac surgery: A systematic review and meta-analysis. J Clin Anesth 73:110308. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jclinane.2021.110308\u003c/span\u003e\u003cspan address=\"10.1016/j.jclinane.2021.110308\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"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-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"delirium, elderly patients, postoperative acute pain, abdominal surgery","lastPublishedDoi":"10.21203/rs.3.rs-6987226/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6987226/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e Against the backdrop of global population aging, the number of elderly patients undergoing surgical procedures continues to increase. These patients frequently experience postoperative acute pain and delirium, however, there is little clinical data on their possible interrelationships.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e A secondary analysis of multicenter prospective data, including tertiary hospitals in Five Chinese Regions, from April 2020 to April 2022 .Elderly patients (\u0026ge;\u0026thinsp;65 years) scheduled for elective abdominal surgery under general anesthesia, without auditory, visual, or cognitive impairments, who completed assessments for postoperative delirium, anxiety, and depression.The impact of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery was evaluated using univariate and multivariate logistic regression, propensity score matching, and subgroup analysis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e This study included 2,674 patients. Delirium occurred in 13.2% (n\u0026thinsp;=\u0026thinsp;354) of patients in postoperative 7 days (POD 7), with significantly higher prevalence in the moderate-to-severe pain group (unadjusted: 16.3 vs. 9.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moderate-to-severe pain on POD1 showed a significant association with delirium occurrence in POD 7 according to univariate logistic regression (OR 1.831, 95% CI 1.445 to 2.319, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), multivariable logistic regression (OR 1.629, 95% CI 1.274 to 2.084, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and propensity score matching (PSM) model (OR 1.443, 95% CI 1.108 to 1.879, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e In elderly patients undergoing elective abdominal surgery, moderate-to-severe pain on POD 1 was significantly associated with both delirium and depressive symptoms within 7 days of surgery. Improved early postoperative analgesic strategies may aid in preventing delirium.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTRIAL REGISTRATION\u003c/b\u003e ClinicalTrials.gov identifier: NCT06964893 (2025-05-07 )\u003c/p\u003e","manuscriptTitle":"The effect of early postoperative acute pain on postoperative delirium in elderly patients undergoing abdominal surgery:a secondary analysis of multicenter prospective data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 11:24:03","doi":"10.21203/rs.3.rs-6987226/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revisions","date":"2025-10-19T05:40:55+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-07-15T04:45:07+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-09T08:04:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-01T14:00:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Geriatric Medicine","date":"2025-06-26T22:36:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a970b9b9-c643-414b-9f71-596dff7f7730","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-22T10:20:00+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 11:24:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6987226","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6987226","identity":"rs-6987226","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}