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Our study aims to test the hypothesis that intraoperative methylene blue reduces the incidence of postoperative delirium (POD) following major abdominal surgery, and to evaluate the inflammatory biomarkers as potential mediators. A randomized, single blind clinical trial. University cancer center. Three hundred and fourteen patients scheduled for pancreatic surgery. Patients were randomly assigned to methylene blue group, who receiving intravenous infusion of 2 mg kg-1 methylene blue within 60 min immediately after anesthetic induction, followed by infusion of 1 mg kg-1 methylene blue within 30 min before the end of surgery, or control group, who receiving equal volume saline. The primary outcome was POD incidence. The secondary outcomes included plasma interleukin 6 (IL-6) and interleukin 8 (IL-8) concentrations before and after surgery, gene expressions in human brain microvascular endothelial cells (hCMEC/d3) and peripheral blood mononuclear cells (PBMCs) adhesion to hCMEC/d3. Perioperative adverse events were also documented. A total of 55 patients (17.5%) experienced POD, with a lower POD incidence in the methylene blue group than in the control group (11.5% vs. 23.6%, p = 0.005). The adverse events in the two groups were comparable. And postoperative plasma IL-6 but not IL-8 concentration was lower in the methylene blue group. Furthermore, endothelial TNF-α, MCP-1 and VCAM1 expressions were lower when treated with serum from the methylene blue group, and the number of PBMCs adhesion to hCMEC/d3 cells was also less in the methylene blue group. Intraoperative methylene blue use effectively and safely reduced the POD incidence in patients undergoing pancreatic surgery, which may be associated with decrease in systemic inflammation and immunovascular interactions. •Intraoperative methylene blue use effectively and safely reduced the POD incidence in patients undergoing pancreatic surgery.•Compared with control group, systemic IL-6 concentration in the methylene blue group was lower at postoperative first day.•Compared with normal saline, methylene blue significantly mitigated immunovascular interactions in vitro experiments.

There were few clinical data dosing and timing regimen for preventing postoperative delirium. The present study aimed to investigate the effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery. A total of 354 patients >65 years of age undergoing laparoscopic major non-cardiac surgery under general anesthesia received a dexmedetomidine 1 μg/kg bolus followed by 0.2–0.7 μg/kg/h infusion from induction of anesthesia to the end of surgery [group D1]); a dexmedetomidine (1 μg/kg bolus [group D2]); or saline (group S) 15 min before the end of surgery. The incidence and duration of delirium for 5 days after surgery and the cytokine (tumor necrosis factor-alpha TNFα, interleukin [IL]-1 β, IL-2, IL-6, IL-8, and IL-10) and cortisol levels were measured 1 h and 24 h after surgery. Group D1 reduced incidence and duration of delirium and group D2 decreased its duration in patients with delirium compared to group S. IL-6 levels were significantly lower at 1 h and 24 h after surgery in group D1 than in group S, and lower at 24 h after surgery than in group D2. IL-6 levels in group D2 were significantly lower only at 1 h after surgery than in group S. However, IL-6 levels in delirious patients in group D2 were significantly lower at 1 h and 24 h after surgery than those in group S. Cortisol levels 1 h after surgery were significantly lower in groups D1 and D2 than in group S. The dose and timing of dexmedetomidine appeared to be important in preventing delirium. The reduced incidence and duration of delirium by dexmedetomidine was associated with reduced levels of IL-6 24 h after surgery. •Perioperative long duration of dexmedetomidine reduces the incidence and severity of postoperative delirium.•Dexmedetomidines also reduced the inflammatory cytokines such as IL-6.•IL-6 at 24 h after surgery may be an important factor in predicting postoperative delirium.

Objective Cerebral hypoxia and hypoperfusion are key pathophysiological contributors to postoperative delirium (POD). This study evaluated the impact of 40% versus 100% inspired oxygen (FiO₂) on POD incidence, neuroinflammation, and clinical outcomes in elderly patients undergoing major abdominal surgery. Methods In this trial, 160 elderly patients scheduled for major abdominal surgery under general anesthesia from 2022 to September 2023 were randomly assigned to receive 40% FiO₂ ( n  = 80) or 100% FiO₂ ( n  = 80). The primary outcome was POD incidence within 3 postoperative days. Secondary outcomes included perioperative oxygenation parameters, plasma neuroinflammatory markers, pulmonary infections, pain scores, and hospitalization duration. Blood samples were collected preoperatively and postoperatively for biomarker analysis. Results Among 154 analyzed patients, POD incidence was 5.2% (8/154), with no significant difference between 40% FiO₂ (6.4%, 5/78) and 100% FiO₂ (3.9%, 3/76) groups ( P  = 0.72). The 40% FiO₂ group exhibited lower saturation of pulse oxygen, regional cerebral oxygen saturation, and arterial partial pressure of oxygen from 1 h post-anesthesia (T2) to anesthesia end (T5) ( P  < 0.05). No intergroup differences in interleukin-6, tumor necrosis factor alpha, neuron-specific enolase, or neurofilament light chain levels were observed postoperatively ( P  > 0.05). FiO₂ levels did not influence pulmonary infection rates, postoperative VAS scores, or hospital stay ( P  > 0.05). Conclusions While 100% FiO₂ enhances cerebral oxygenation, it does not reduce POD incidence or neuroinflammatory markers compared to 40% FiO₂. High-concentration oxygen did not increase pulmonary complications but offered no clinical benefits in this cohort. Intraoperative FiO₂ should be titrated based on individualized patient needs.

IntroductionPostoperative delirium (POD) is a common and serious postoperative complication, with an incidence of approximately 30% among older adults undergoing gastrointestinal surgery. Serotonin has been implicated in a variety of neuropsychiatric disorders. Gastrointestinal surgery has been shown to increase serotonin synthesis and release from enterochromaffin cells; however, the causal relationship between serotonin and POD remains unclear. This study aims to investigate the causal relationship between peripheral serotonin levels and POD in older adults undergoing gastrointestinal surgery.Methods and analysisThis single-centre prospective cohort study will enrol 314 patients aged ≥60 years who are undergoing elective gastrointestinal surgery at the Affiliated Hospital of Qingdao University between December 2025 and December 2026. Peripheral serotonin levels will be measured prior to anaesthesia induction and prior to discharge from the post-anaesthesia care unit. The primary outcome will be the incidence of POD within 3 days. Secondary outcomes will include emergence agitation, number of POD episodes, POD onset time and duration, POD severity and subtype, pain scores, quality of recovery, gastrointestinal function and postoperative complications. A predefined directed acyclic graph will be used to guide covariate adjustment. Statistical analyses will include multivariate logistic regression, linear trend analysis, restricted cubic spline modelling, subgroup analyses, sensitivity analyses and Bayesian mediation analysis. Delirium assessors will undergo standardised training conducted by psychiatrists to ensure diagnostic reliability.Ethics and disseminationThe study protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No. QYFYEC2025-199) and was registered with the Chinese Clinical Trial Registry (Registration ChiCTR2500112152). Written informed consent will be obtained from all participants prior to enrolment. Data will be anonymised, securely stored on encrypted servers for a minimum of 10 years, and shared only with approval from the ethics committee. Results will be disseminated through publication in peer-reviewed journals and presentation at scientific conferences.Trial registration numberChiCTR2500112152.

ObjectiveThis study aims to investigate the role of fast-track surgery in preventing the development of postoperative delirium and other complications in elderly patients with colorectal carcinoma.MethodsA total of 240 elderly patients with colorectal carcinoma (aged ≥70 years) undergoing open colorectal surgery was randomly assigned into two groups, in which the patients were managed perioperatively either with traditional or fast-track approaches. The length of hospital stay (LOS) and time to pass flatus were compared. The incidence of postoperative delirium and other complications were evaluated. Serum interleukin-6 (IL-6) levels were determined before and after surgery.ResultsThe LOS was significantly shorter in the fast-track surgery (FTS) group than that in the traditional group. The recovery of bowel movement (as indicated by the time to pass flatus) was faster in the FTS group. The postoperative complications including pulmonary infection, urinary infection and heart failure were significantly less frequent in the FTS group. Notably, the incidence of postoperative delirium was significantly lower in patients with the fast track therapy (4/117, 3.4 %) than with the traditional therapy (15/116, 12.9 %; p = 0.008). The serum IL-6 levels on postoperative days 1, 2, and 3 in patients with the fast-track therapy were significantly lower than those with the traditional therapy (p < 0.001).ConclusionsCompared to traditional perioperative management, fast-track surgery decreases the LOS, facilitates the recovery of bowel movement, and reduces occurrence of postoperative delirium and other complications in elderly patients with colorectal carcinoma. The lower incidence of delirium is at least partly attributable to the reduced systemic inflammatory response mediated by IL-6.

Postoperative delirium (POD) is common in elderly patients undergoing laparoscopic surgery for gastric and colorectal malignancies. POD may be affected by different fraction of inspired oxygen (FiO ). The purpose of this study was to compare the effects of different FiO on POD. A randomized, double-blind controlled trial was performed in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 662 patients aged 65 to 85 years old underwent isolated laparoscopic radical gastrectomy, radical resection of colon cancer, or radical resection of rectal cancer only. A random number table method was used to divide the patients into two groups: 40% FiO (group A) and 80% FiO (group B). The primary endpoint was the incidence of POD, which was assessed by the Confusion Assessment Method (CAM) twice daily during the first 7 postoperative days, and POD severity was measured by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the intraoperative regional cerebral oxygen saturation (rSO ), Bispectral (BIS) index, invasive arterial blood pressure (IABP), oxygen saturation (SpO ), end-tidal carbon dioxide partial pressure (P CO ), the number of atelectasis cases and visual analogue scale (VAS) scores on days 1-7 after surgery. The incidence of POD was 19.37% (122/630), including 20.38% (64/314) in group A and 18.35% (58/316) in group B. No statistical significance was found in the incidence of POD between the two groups ( > 0.05); compared with group B, SpO , rSO and PaO decreased at T to T time point ( < 0.01), and the incidence of postoperative atelectasis decreased ( < 0.05) in group A. The incidence of POD was not significantly affected by different FiO and the incidence of postoperative atelectasis was decreased at low FiO .

Objective Postoperative delirium, a common neurocognitive complication after surgery and anesthesia, requires early detection for potential intervention. Herein, we constructed a multidimensional postoperative delirium risk‐prediction model incorporating multiple demographic parameters and blood biomarkers to enhance prediction accuracy. Methods We included 555 patients undergoing radical surgery for colorectal cancer. Demographic characteristics and lipid profiles were collected preoperatively, and perioperative anesthesia and surgical conditions were recorded; blood biomarkers were measured before and after surgery. The 3D‐CAM scale was used to assess postoperative delirium occurrence within 3 days after surgery. Patients were divided into the postoperative delirium (N = 100) and non‐postoperative delirium (N = 455) groups. Based on machine learning, linear and nine non‐linear models were developed and compared to select the optimal model. Shapley value‐interpretation methods and mediation analysis were used to assess feature importance and interaction. Results The median age of the participants was 65 years (interquartile range: 56–71 years; 57.8% male). Among the 10 machine‐learning models, the random forest model performed the best (validation cohort, area under the receiver operating characteristic curve of 0.795 [0.704–0.885]). Lipid profile (total cholesterol, triglycerides, and trimethylamine‐N‐oxide) levels were identified as key postoperative delirium predictors. Mediation analysis further confirmed mediating effects among total cholesterol, trimethylamine‐N‐oxide, and postoperative delirium; a nomogram model was developed as a web‐based tool for external validation and use by other clinicians. Interpretation Blood biomarkers are crucial in predicting postoperative delirium and aid anesthesiologists in identifying its risks in a timely manner. This model facilitates personalized perioperative management and reduces the occurrence of postoperative delirium. Trial Registration ChiCTR2300075723

Introduction Cerebrospinal fluid Aβ42 has been proposed as a potential indicator for cerebral β‐amyloidosis and may be involved in the pathophysiology of delirium. Whether perioperative plasma Aβ42 alternation is associated with postoperative delirium risk among elderly patients remains unknown. Methods This was a secondary analysis of a randomized controlled trial evaluating the effects of acupuncture (intervention) compared to standard care (control) on the incidence of delirium in patients undergoing major abdominal surgery. Participants with blood samples collected were included in this cohort study. The exposure variable was the Aβ42 ratio, calculated with the plasma Aβ42 level immediately after surgery divided by the preoperative plasma Aβ42 level. The primary endpoint was the occurrence of delirium within the first 7 days following surgery or until hospital discharge, whichever happened first, evaluated using either the Confusion Assessment Method or the Confusion Assessment Method‐intensive care unit for intubated patients. Delirium severity was a secondary outcome assessed by the Memorial Delirium Assessment Scale. The logistic regression models and a restricted cubic spline were performed to examine the association between the Aβ42 ratio and delirium incidence, with receiver operating characteristic curve (ROC) analysis for diagnostic power. The mediation effects of the matrix metalloproteinase‐9 ratio were further explored by causal mediation analysis. The linear regression and generalized linear mixed models assessed the association between the Aβ42 ratio and delirium severity. Results A total of 195 patients with blood samples collected were included in the final analysis. Among them, the mean age was 70.2 ± 4.2 years; 134 were female (68.7%), and 26 (13.3%) patients experienced postoperative delirium. The plasma Aβ42 ratio was positively correlated with an increased delirium risk (adjusted odds ratio 3.21, 95% confidence interval 1.71–6.05, p < 0.001) and delirium severity, as measured by the highest postoperative Memorial Delirium Assessment Scale score (adjusted β coefficient 3.04, 95% confidence interval 0.9–5.18, p = 0.006) in the fully adjusted multivariable analysis models. The restricted cubic spline indicated a linear relationship between the plasma Aβ42 ratio and delirium incidence (p = 0.202). The ROC showed that the area under the curve for the Aβ42 ratio to predict delirium risk was 0.698 (95% CI, 0.582–0.814), with the optimal cut‐off point of 0.137. Mediation analyses showed that the Aβ42 ratio does not mediate postoperative delirium through the matrix metalloproteinase‐9 ratio (proportion: 1.3%). Conclusions This cohort study showed that a higher Aβ42 ratio was associated with an increased delirium risk and severity, and the association was linear. The plasma Aβ42 ratio might be a mini‐invasive biomarker to identify postoperative delirium. In a secondary analysis of a randomized controlled trial, we investigated the plasma Aβ42 ratio's association with delirium risk and severity in elderly patients undergoing abdominal surgery. The results showed that a higher Aβ42 ratio was associated with an increased delirium risk and severity, and the association was linear.

Background The inflammatory cell product neopterin is elevated in serum before and during delirium. This suggests a role for disordered cell-mediated immunity or oxidative stress. Cerebrospinal fluid (CSF) neopterin levels reflect brain neopterin levels more closely than serum levels. Here we hypothesized that CSF neopterin levels would be higher in delirium. Methods In this prospective cohort study, 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh. Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively. Paired CSF and blood samples were collected at the onset of spinal anaesthesia. Neopterin levels were measured using high-performance liquid chromatography. Results Sixty-four (46 %) of 139 hip fracture patients developed delirium perioperatively. CSF neopterin levels were higher in delirium compared to controls (median 29.6 vs 24.7 nmol/mL, p  = 0.003), with highest levels in patients who developed delirium post-operatively. Serum neopterin levels were also higher in delirium (median 37.0 vs 27.1 nmol/mL, p  = 0.003). CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors. Higher neopterin levels were associated with poorer outcomes (death or new institutionalization) 1 year after surgery ( p  = 0.02 for CSF and p  = 0.03 for serum). Conclusions This study is the first to examine neopterin in CSF from patients with delirium. Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process. High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes.

Aim The pathophysiology of delirium remains elusive though neurotransmitters and their precursor large neutral amino acids (LNAAs) may play a role. This pilot study investigated whether alterations of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) plasma levels were associated with a higher risk of transitioning to delirium in critically ill patients. Methods Plasma LNAA concentrations were determined on days 1 and 3 in mechanically ventilated (MV) patients from the MENDS randomized controlled trial (dexmedetomidine vs. lorazepam sedation). Three independent variables were calculated by dividing plasma concentrations of Trp, Phe, and Tyr by the sum of all other LNAA concentrations. Delirium was assessed daily using the confusion assessment method for the intensive care unit (CAM-ICU). Markov regression models were used to analyze independent associations between plasma LNAA ratios and transition to delirium after adjusting for covariates. Results The 97 patients included in the analysis had a high severity of illness (median APACHE II, 28; IQR, 24–32). After adjusting for confounders, only high or very low tryptophan/LNAA ratios ( p  = 0.0003), and tyrosine/LNAA ratios ( p  = 0.02) were associated with increased risk of transitioning to delirium, while phenylalanine levels were not ( p  = 0.27). Older age, higher APACHE II scores and increasing fentanyl exposure were also associated with higher probabilities of transitioning to delirium. Conclusions In this pilot study, plasma tryptophan/LNAA and tyrosine/LNAA ratios were associated with transition to delirium in MV patients, suggesting that alterations of amino acids may be important in the pathogenesis of ICU delirium. Future studies evaluating the role of amino acid precursors of neurotransmitters are warranted in critically ill patients.