Impact of Dexmedetomidine on Hemodynamics, Plasma Catecholamine Levels, and Delirium Incidence Among Intubated Patients in the ICU--A Randomized Controlled Trial.

Objective: To investigate the impact of various sedative medications on hemodynamics and plasma levels of epinephrine (E) and norepinephrine (NE) in mechanically ventilated patients postoperatively in the intensive care unit (ICU). Methods: Ninety-seven patients admitted to the ICU undergoing postoperative mechanical ventilation with tracheal intubation and continuous analgesic sedation following general anesthesia were randomly assigned to either the observation group (dexmedetomidine) (n = 49) or the control group (propofol) (n = 48) in this randomized controlled trial. Upon transfer to the ICU, vital signs (heart rate [HR], respiratory rate [RR], mean arterial pressure [MAP]) were recorded prior to the initiation of the sedation treatment (T0), at one-hour post sedation (T1) and two hours following tracheal extubation (T2), plasma levels of epinephrine (E) and norepinephrine (NE) were measured at these time points. The incidence of delirium was recorded in both groups. Results: MAP between the two groups at both T0 and T1 At T2 plasma NE and HR were found to be lower in the observation group compared to the control group (P < 0.001). Among the patients receiving antihypertensive medication in the ICU, NE levels were significantly lower in the observation group compared to the control group (P = 0.019) Among the patients not receiving antihypertensive medication, both NE (P < 0.001) and MAP (P = 0.001) levels were lower in the observation group compared to the control group. The incidence of delirium in the observation group (dexmedetomidine) was not significantly different from that in the control group (propofol). Conclusion: With dexmedetomidine sedation, blood pressure fluctuated less, plasma catecholamine levels were lower, and sympathetic inhibition was stronger in patients before and after extubation. However, it did not significantly reduce the incidence of postoperative delirium.

Using Machine Learning and Electronic Health Records to Identify Neuropsychiatric Risk Scores for Delirium in ICU and General Hospital Settings.

Objective: Delirium is a common and acute neuropsychiatric syndrome that requires timely intervention to prevent its associated morbidity and mortality. Yet, its diagnosis and symptoms are often overlooked due to its variable clinical presentation and fluctuating nature. Thus, in this study, we address the barriers to delirium diagnosis by utilizing a machine learning-based predictive algorithm for incident delirium that relies on archived electronic health records (EHRs) data. Methods: We used the Medical Information Mart for Intensive Care (MIMIC) database to create a detailed dataset for identifying delirium in intensive care unit (ICU) patients. Our approach involved training machine learning models on this dataset to pinpoint critical clinical features for delirium detection. These features were then refined and applied to non-ICU patients using EHRs from the American University of Beirut Medical Center (AUBMC). Results: Our study assessed machine learning models like Extreme Gradient Boosting (XGBoost), Categorical Boosting (CatBoost), Classification and Regression Trees (CART), Random Forest (RF), Neural Oblivious Decision Ensembles (NODE), and Logistic Regression (LR), highlighting superior delirium detection in diverse clinical settings. The CatBoost model excelled in ICU environments with an F1 Score of 89.2%, while XGBoost performed best in general hospital settings with a 75.4% F1 Score. Interpretations using Tabular Local Interpretable Model-agnostic Explanations (LIME) revealed critical indicators such as prothrombin time and hematocrit levels, enhancing model transparency and clinical applicability. These clinical insights help differentiate the delirium predictors between ICU patients, who are often sensitive to various factors. Conclusion: The proposed predictive algorithm improves delirium detection rates and streamlines efficiency in hospital electronic systems, thereby enabling prompt interventions to prevent delirium progression and associated complications. The clinical indicators for delirium that we identified in general hospital settings and ICU can greatly help healthcare professionals identify potential causes of delirium and reduce misdiagnosis.

Impact of dexmedetomidine-assisted anesthesia in elderly patients undergoing radical resection of colon cancer.

BACKGROUND: Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy. However, due to the physiological characteristics of elderly patients, the safety of perioperative anesthesia needs special attention. As an α2-adrenergic receptor agonist, dexmedetomidine (Dex) has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure, inhibitory effect on inflammation, and sedative and analgesic effects. Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer. AIM: To investigate the anesthetic effects of Dex during radical surgery for colon cancer under general anesthesia in elderly patients. METHODS: A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital, Qingdao, China were recruited and divided into two groups: A and B. In group A, Dex was administered 30 min before surgery, while group B received an equivalent amount of normal saline. The hemodynamic changes, pulmonary compliance, airway pressure, inflammatory factors, confusion assessment method scores, Ramsay Sedation-Agitation Scale scores, and cellular immune function indicators were compared between the two groups. RESULTS: Group A showed less intraoperative hemodynamic fluctuations, better pulmonary compliance, and lower airway resistance compared with group B. Twelve hours after the surgery, the serum levels of TLR-2, TLR-4, IL-6, and TNF-α in group A were significantly lower than those of group B (P < 0.05). After extubation, the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients, indicating a higher level of sedation. The incidence of delirium was significantly lower in group A than in group B (P < 0.05). CONCLUSION: The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.

You are safe here: A flyer with re-orientating messages for families of patients with delirium in the intensive care unit.

Patients in delirium require trustful communication and re-orientation. We developed a flyer with positive, re-orientating suggestions for families of delirious patients in intensive care units. Suggestions include creating a safe environment, interpreting unusual behaviours positively and fostering mental resilience. Additionally, families are encouraged to prioritize their own well-being, recognizing their crucial role in supporting their loved ones. This flyer offers practical strategies across four key areas: ensuring security and orientation, reframing noises and body experiences, managing agitation and reshaping perceptions. By equipping families with knowledge and tools, this resource aims to promote understanding, resilience and strength to humanize delirium care.

The hot spots and global trends of prevention and treatment in postoperative delirium (POD) from 2004 to 2023: A bibliometric analysis.

Background: Postoperative delirium (POD) is an acute postoperative syndrome of the central nervous system that seriously affects the prognosis of patients. Many vital advances have been made in the study of the management of POD. We conducted a bibliometric analysis of research on the prevention and treatment of POD over the past 20 years to consolidate current research focal points and emerging trends in this domain. Methods: We searched the Web of Science Core Collection database for literature published between 2004 and 2023. VOSviewer, CiteSpace, Microsoft Excel, Scimago Graphica, and the R tool "bibliometrix" were used to analyze and visualize annual publications, countries, organizations, journals, authors, keywords, and references. Results: A total of 1848 eligible publications were identified, with a general uptrend observed in both annual publications and citations. The USA was the most profitable country, ranking first in total publications. The most active institution was Harvard Medical School. Inouye, Sharon K was the most prolific scholar due to her numerous publications and citations. According to the co-occurrence network, the strongest citation bursts and co-cited references analysis fresh hot topics included "dexmedetomidine," "neuroinflammation," "haloperidol prophylaxis," and "guideline." Conclusions: Research on prevention and treatment of POD is gaining significant momentum worldwide. Current hot spots include early perioperative prevention strategies and integrated multi-method treatments. Effective drugs for it is one of the directions in the future. The management of pediatric patients with POD has caused concern in recent years. This bibliometric analysis is poised to guide future research trajectories in this field.

Nutritional Status and Inflammation as Mediators of Physical Performance and Delirium in Elderly Community-Acquired Pneumonia Patients: A Retrospective Cohort Study.

Purpose: This study proposes a multiple mediation model to evaluate the association among diminished physical performance, malnutrition, inflammation, and delirium in seniors with community-acquired pneumonia. Patients and Methods: This retrospective cohort study included elderly patients hospitalized for community-acquired pneumonia at the Geriatrics Department of the Second People's Hospital of Lianyungang from January 1, 2020, to January 1, 2024. Logistic regression analysis was conducted to examine the associations among physical performance, nutritional status, C-reactive protein (CRP) levels, and delirium. Mediation models assessed the effects of nutritional status and CRP on the relationship between physical performance and delirium, with subgroup analyses based on diabetes status. Results: A total of 379 patients were included, with a mean age of 80.0±7.4 years, and 51.7% were male. The incidence of delirium during hospitalization was 28.5% (n=108). Subgroup analyses revealed significant correlations between physical performance, nutritional status, and CRP (P<0.001), regardless of diabetes status. After adjusting for confounding variables, CRP was positively associated with delirium, while MNA-SF and SPPB scores showed negative correlations with delirium risk (OR=0.852, 95% CI: 0.730-0.995; OR=0.580, 95% CI: 0.464-0.727, P<0.05). Mediation analyses indicated that MNA-SF scores and CRP significantly mediated the association between SPPB and delirium. Specifically, pathways "SPPB→ MNA-SF→ delirium", "SPPB→ CRP→ delirium", and "SPPB→ MNA-SF→ CRP→ delirium" demonstrated significant mediating effects in patients without diabetes, while only the pathway "SPPB→ MNA-SF→ CRP→ delirium" was significant in those with diabetes. Conclusion: Older patients with community-acquired pneumonia and poor physical performance are more susceptible to delirium, with nutritional status and inflammation as key mediators.

Perioperative Risk Factors for Postoperative Delirium in Non-Dementia Older Patients after Non-Cardiac Surgery and Anesthesia: A Prospective Study.

Background: To investigate the incidence and perioperative risk factors for postoperative delirium (POD) in non-dementia older patients who underwent anesthesia for non-cardiac surgery. Methods: This prospective cohort study was conducted on 195 non-dementia older patients, aged 60 years or older, who were hospitalized after non-cardiac surgery and anesthesia. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was used to evaluate the occurrence of POD. Incidence of POD was reported. We conducted univariate and multivariate logistic regression to identify the risk factors associated with POD. Results: 195 patients were enrolled; 172 completed the study. POD occurred in seven patients within three days after anesthesia, which is a 4.1% incidence of POD. Multivariate logistic analysis showed arrhythmia, coagulopathy, urinary comorbidity, minimum intraoperative heart rate, and minimum post-anesthesia care unit (PACU) pain score as independent risk factors for POD. A minimum PACU pain score > 1 is the optimum cutoff pain score for developing POD, with a sensitivity of 85.7% and a specificity of 69.1%. The postoperative complication rate and in-hospital mortality were significantly higher for patients with POD compared to those without POD. Conclusion: The incidence of POD in the study population is 4.1%. Arrhythmia, coagulopathy, urinary comorbidity, minimum intraoperative heart rate, and minimum PACU pain score were independent risk factors for POD. The minimum PACU pain score is the strongest independent risk factor of POD. POD is associated with increased postoperative complications and in-hospital mortality rates in non-dementia older patients.

Gut Microbiota and Probiotics in Perioperative Management: A Narrative Review.

The human gut is the abode of several complex and diverse microbes. It is a fact that the human brain is interconnected with the spinal cord and sense organs; however, there is also a possibility of a connection between the brain and the gut microbiome. The human gut can be altered in various ways, the principal method being the intake of prebiotics, probiotics and synbiotics. Can this alteration in the gut microbiome be clinically utilised in the perioperative period? We conducted a literature search related to this topic using databases and search engines (Medical Literature Analysis and Retrieval System Online {MEDLINE}, Embase, Scopus, PubMed and Google Scholar). The search revealed some preclinical and clinical studies in animals and humans that demonstrate the alteration of the gut microbiome with the use of anxiolysis, probiotics/prebiotics and other perioperative factors including opioids, anaesthetics and perioperative stress. The significant effects of this alteration have been seen on preoperative anxiety and postoperative delirium/cognitive dysfunction/pain. These effects are described in this narrative review, which opens up newer vistas for high-quality research related to the gut microbiome, gut-brain axis, the related signaling pathways and their clinical application in the perioperative period.

Author Response: Nocturnal Infusion of Low-dose Dexmedetomidine and Propofol for Delirium Prevention.

How to cite this article: Ekkapat G, Chokengarmwong N. Author Response: Nocturnal Infusion of Low-dose Dexmedetomidine and Propofol for Delirium Prevention. Indian J Crit Care Med 2024;28(9):896.

Nocturnal Infusion of Low-dose Dexmedetomidine and Propofol for Prevention of Delirium Occurring in the ICU after Hip Fracture Surgery in Elderly Patients.

How to cite this article: Cong N, Wang D, Xue F. Nocturnal Infusion of Low-dose Dexmedetomidine and Propofol for Prevention of Delirium Occurring in the ICU after Hip Fracture Surgery in Elderly Patients. Indian J Crit Care Med 2024;28(9):894-895.

Dexmedetomidine for Postoperative Delirium Prevention in the Older Adult: An Integrative Review.

The brain and cognition are particularly vulnerable to anesthetic and surgical insults, with postoperative delirium being the most common postoperative complication in patients aged ≥ 65 years. The body releases psychoactive proinflammatory cytokines in response to surgical trauma, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α. This promotes a porous blood-brain barrier, promoting postoperative cognitive dysfunction. Aging adults lose brain volume, cerebrospinal fluid, and dendritic synapses, thereby increasing neurologic stress and vulnerability to these surgical changes. Anesthetic technique influences the process, necessitating the importance of educated certified registered nurse anesthetists. Dexmedetomidine, a nonspecific α2-adrenergic receptor agonist, exhibits anti-inflammatory properties that counteract the proinflammatory mechanisms initiated by surgical insult. Additionally, dexmedetomidine mimics natural sleep pathways and reduces opioid dosing requirements, promoting cognitive preservation. While further research is required to establish an association with long-term effects, current literature indicates that dexmedetomidine may reduce postoperative delirium and cognitive dysfunction in older adults through various dosing regimens. This journal course reviews the pathophysiology of postoperative neurocognitive dysfunction and delirium, dexmedetomidine as an adjunct to mitigate these pathologic changes, and the current literature on dexmedetomidine's impact on postoperative delirium in older adults.

Postoperative Delirium and Neurocognitive Disorders: A Comprehensive Review of Pathophysiology, Risk Factors, and Management Strategies.

Postoperative delirium (POD) and neurocognitive disorders (NCDs) are common and serious complications that can occur after surgery, particularly in older adults and those with preexisting cognitive impairments. These conditions are associated with significant morbidity, increased healthcare costs, and reduced quality of life. Understanding the underlying mechanisms, risk factors, and effective management strategies for POD and NCDs is critical for improving patient outcomes and reducing the burden on healthcare systems. This comprehensive review aims to synthesize current knowledge on the pathophysiology, risk factors, and management strategies for POD and NCDs. It explores the neurobiological and molecular mechanisms contributing to these conditions, identifies the patient-related, surgical, and environmental factors that increase risk, and evaluates pharmacological and non-pharmacological approaches to prevention and treatment. A thorough literature review was conducted using recent studies, clinical guidelines, and expert consensus to provide a detailed overview of the pathophysiology, risk factors, clinical presentation, prevention, and management of POD and NCDs. The pathophysiology of POD and NCDs involves complex interactions between neuroinflammatory processes, neurotransmitter imbalances, and brain network disruptions. Risk factors include advanced age, preexisting cognitive impairment, type and duration of surgery, and perioperative complications. Management strategies emphasize a multidisciplinary approach, incorporating preoperative optimization, careful intraoperative management, and postoperative interventions. Pharmacological treatments, such as antipsychotics, and non-pharmacological approaches, including environmental modifications and cognitive rehabilitation, play crucial roles in management. Postoperative delirium and NCDs are multifactorial conditions with significant impacts on surgical outcomes. Effective management requires a comprehensive understanding of their pathophysiology and risk factors and the implementation of targeted prevention and treatment strategies. Future research should focus on personalized approaches to prevention and treatment, further elucidation of mechanisms, and developing predictive models to enhance care for patients at risk of these neurocognitive complications.

Utilization of NIRS Monitor to Compare the Regional Cerebral Oxygen Saturation Between Dexmedetomidine and Propofol Sedation in Mechanically Ventilated Critically ill Patients with Sepsis- A Prospective Randomized Control Trial.

AIM & BACKGROUND: Delirium frequently occurs in the acute phase of sepsis and is associated with increased ICU and hospital length of stay, duration of mechanical ventilation, and higher mortality rates. We utilized the Near-Infrared Spectroscopy monitor to measure and compare the regional cerebral oxygen saturation in mechanically ventilated patients of sepsis receiving either dexmedetomidine or propofol sedation and assessed the association between delirium and regional cerebral oxygen saturation. METHODS: A single center prospective randomized control trial conducted over a period of two years, 54 patients were included, equally divided between propofol and dexmedetomidine groups. Patients received a blinded study drug, propofol (10 mg/mL) or dexmedetomidine (5 mcg/mL) via infusion pump according to randomization. Infusion rates were adjusted every 10 min based on weight-based titration tables, aiming for target sedation (RASS -2 to 0). Management components included pain monitoring using the CPOT score and delirium assessment using CAM-ICU score. RESULTS: Dexmedetomidine group showed higher mean regional cerebral oxygen saturation as compared to propofol group (P = .036). No significant differences were found in mechanical ventilation or ICU stay durations, delirium-free days, or sedation cessation reasons. Delirium occurred in 36 patients, with lower mean regional cerebral oxygen saturation as compared to non-delirious patients. CONCLUSION: The dexmedetomidine group had higher regional cerebral oxygen saturation compared to the propofol group. Delirious patients showed lower cerebral oxygen saturation than non-delirious patients, suggesting a link between sedation type, cerebral oxygenation, and delirium.CTRI registration: REF/2021/11/048655 N.

Corrigendum: Frailty index and risk of delirium in hospitalized patients: a two-sample Mendelian randomization study.

[This corrects the article DOI: 10.3389/fmed.2024.1361437.].

No substantial neurocognitive impact of COVID-19 across ages and disease severity: a multicenter biomarker study of SARS-CoV-2 positive and negative adult and pediatric patients with acute respiratory tract infections.

BACKGROUND: Compared to intensive care unit patients with SARS-CoV-2 negative acute respiratory tract infections, patients with SARS-CoV-2 are supposed to develop more frequently and more severely neurologic sequelae. Delirium and subsequent neurocognitive deficits (NCD) have implications for patients' morbidity and mortality. However, the extent of brain injury during acute COVID-19 and subsequent NCD still remain largely unexplored. Body-fluid biomarkers may offer valuable insights into the quantification of acute delirium, brain injury and may help to predict subsequent NCD following COVID-19. METHODS: In a multicenter, observational case-control study, conducted across four German University Hospitals, hospitalized adult and pediatric patients with an acute COVID-19 and SARS-CoV-2 negative controls presenting with acute respiratory tract infections were included. Study procedures comprised the assessment of pre-existing neurocognitive function, daily screening for delirium, neurological examination and blood sampling. Fourteen biomarkers indicative of neuroaxonal, glial, neurovascular injury and inflammation were analyzed. Neurocognitive functions were re-evaluated after three months. RESULTS: We enrolled 118 participants (90 adults, 28 children). The incidence of delirium [85 out of 90 patients (94.4%) were assessable for delirium) was comparable between patients with COVID-19 [16 out of 61 patients (26.2%)] and SARS-CoV-2 negative controls [8 out of 24 patients (33.3%); p > 0.05] across adults and children. No differences in outcomes as measured by the modified Rankin Scale, the Short-Blessed Test, the Informant Questionnaire on Cognitive Decline in the Elderly, and the pediatrics cerebral performance category scale were observed after three months. Levels of body-fluid biomarkers were generally elevated in both adult and pediatric cohorts, without significant differences between SARS-CoV-2 negative controls and COVID-19. In COVID-19 patients experiencing delirium, levels of GFAP and MMP-9 were significantly higher compared to those without delirium. CONCLUSIONS: Delirium and subsequent NCD are not more frequent in COVID-19 as compared to SARS-CoV-2 negative patients with acute respiratory tract infections. Consistently, biomarker levels of brain injury indicated no differences between COVID-19 cases and SARS-CoV-2 negative controls. Our data suggest that delirium in COVID-19 does not distinctly trigger substantial and persistent subsequent NCD compared to patients with other acute respiratory tract infections. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359914; date of registration 24-APR 2020.

Delirium and frailty in older adults: Clinical overlap and biological underpinnings.

Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, and negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms and implement initiatives to reduce the associated burden. This literature review summarizes scientific evidence on the complex interplay between frailty and delirium; clinical, epidemiological, and pathophysiological commonalities; and current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis of the results-carried out by content experts-highlights overlapping risk factors, clinical phenotypes, and outcomes and explores the influence of one syndrome on the onset of the other. Common pathophysiological mechanisms identified include inflammation, neurodegeneration, metabolic insufficiency, and vascular burden. The review suggests that frailty is a risk factor for delirium, with some support for delirium associated with accelerated frailty. The proposed unifying framework supports the integration and measurement of both constructs in research and clinical practice, identifying the geroscience approach as a potential avenue to develop strategies for both conditions. In conclusion, we suggest that frailty and delirium might be alternative-sometimes coexisting-manifestations of accelerated biological aging. Clinically, the concepts addressed in this review can help approach older adults with either frailty or delirium from a different perspective. From a research standpoint, longitudinal studies are needed to explore the hypothesis that specific pathways within the biology of aging may underlie the clinical manifestations of frailty and delirium. Such research will pave the way for future understanding of other geriatric syndromes as well.

Optimizing ChatGPT's Interpretation and Reporting of Delirium Assessment Outcomes: Exploratory Study.

BACKGROUND: Generative artificial intelligence (AI) and large language models, such as OpenAI's ChatGPT, have shown promising potential in supporting medical education and clinical decision-making, given their vast knowledge base and natural language processing capabilities. As a general purpose AI system, ChatGPT can complete a wide range of tasks, including differential diagnosis without additional training. However, the specific application of ChatGPT in learning and applying a series of specialized, context-specific tasks mimicking the workflow of a human assessor, such as administering a standardized assessment questionnaire, followed by inputting assessment results in a standardized form, and interpretating assessment results strictly following credible, published scoring criteria, have not been thoroughly studied. OBJECTIVE: This exploratory study aims to evaluate and optimize ChatGPT's capabilities in administering and interpreting the Sour Seven Questionnaire, an informant-based delirium assessment tool. Specifically, the objectives were to train ChatGPT-3.5 and ChatGPT-4 to understand and correctly apply the Sour Seven Questionnaire to clinical vignettes using prompt engineering, assess the performance of these AI models in identifying and scoring delirium symptoms against scores from human experts, and refine and enhance the models' interpretation and reporting accuracy through iterative prompt optimization. METHODS: We used prompt engineering to train ChatGPT-3.5 and ChatGPT-4 models on the Sour Seven Questionnaire, a tool for assessing delirium through caregiver input. Prompt engineering is a methodology used to enhance the AI's processing of inputs by meticulously structuring the prompts to improve accuracy and consistency in outputs. In this study, prompt engineering involved creating specific, structured commands that guided the AI models in understanding and applying the assessment tool's criteria accurately to clinical vignettes. This approach also included designing prompts to explicitly instruct the AI on how to format its responses, ensuring they were consistent with clinical documentation standards. RESULTS: Both ChatGPT models demonstrated promising proficiency in applying the Sour Seven Questionnaire to the vignettes, despite initial inconsistencies and errors. Performance notably improved through iterative prompt engineering, enhancing the models' capacity to detect delirium symptoms and assign scores. Prompt optimizations included adjusting the scoring methodology to accept only definitive "Yes" or "No" responses, revising the evaluation prompt to mandate responses in a tabular format, and guiding the models to adhere to the 2 recommended actions specified in the Sour Seven Questionnaire. CONCLUSIONS: Our findings provide preliminary evidence supporting the potential utility of AI models such as ChatGPT in administering standardized clinical assessment tools. The results highlight the significance of context-specific training and prompt engineering in harnessing the full potential of these AI models for health care applications. Despite the encouraging results, broader generalizability and further validation in real-world settings warrant additional research.

Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury.

Delirium is associated with the risk of future long-term cognitive impairment, but the degree to which markers of neuronal injury may be distinct or shared with dementia has yet to be comprehensively described. We investigated CSF biomarkers of dementia, astrocytosis and neuronal damage in a clinical cohort with persistent delirium, comparing them with an outpatient memory clinic sample. Our aim was to determine if different patterns of biomarker changes could implicate specific mechanisms for delirium-related neuronal injury over and above that attributable to comorbid dementia. We recruited 35 participants from the Prince of Wales Hospital, Sydney, Australia. We included inpatients with delirium persisting for at least 5 days (n = 15, 10 with underlying dementia) and participants from outpatient memory clinics (n = 20, 17 with dementia). CSF assays were as follows: amyloid-ß42, amyloid-ß40, phosphorylated tau181, neurofilament light chain and glial fibrillary acidic protein. We used propensity score matching to estimate effect sizes for each standardized CSF biomarker separately for persistent delirium (irrespective of underlying dementia) and dementia (irrespective of superimposed delirium). Compared with individuals without delirium, persistent delirium was associated with elevated glial fibrillary acidic protein (normalized coefficient per transformed standard deviation, ß = 0.85; 95% confidence interval: 0.03-1.68) and neurofilament light chain (ß = 1.1; 95% confidence interval: 0.5-1.6), but not phosphorylated tau181. Compared with individuals without dementia, glial fibrillary acidic protein, neurofilament light chain and phosphorylated tau181 were all increased to expected levels in dementia cases, with the former two biomarkers at levels comparable to those seen in persistent delirium [glial fibrillary acidic protein (ß = 1.54; 95% confidence interval: 1.05-2.0) and neurofilament light chain (ß = 0.65; 95% confidence interval: 0.24-1.1)]. Persistent delirium was linked with changes in CSF biomarkers not necessarily attributable to dementia. These findings support the potential that delirium is associated with direct neuronal injury independent of dementia pathophysiology. Whether this neuronal injury involves astrocyte dysfunction or direct axonal damage are both possibilities. Future work examining acute brain injury in delirium is needed.

Postoperative Altered Mental Status: A Case Report and Diagnostic Dilemma.

Postoperative altered mental status (AMS) is a prevalent and complex issue that poses a significant diagnostic challenge in the clinical setting. Clinical presentation consists of cognitive disturbances that can range from mild confusion to coma. Given the complexity and variability of AMS, each patient requires a careful and thorough evaluation to identify the underlying cause. Thus, we present a case of a 57-year-old male with confirmed left knee septic arthritis, whose admission was complicated by AMS following several incision and drainage procedures. We highlight the importance of considering a broad differential diagnosis when evaluating postoperative AMS, including electrolyte disturbances and systemic conditions. The case also discusses the importance of early recognition, interdisciplinary collaboration, and a comprehensive diagnostic strategy. By adopting a comprehensive and collaborative approach, healthcare providers can optimize patient outcomes and minimize complications in postoperative AMS cases. The patient's AMS was ultimately attributed to a combination of metabolic disturbances, drug-related factors, and systemic conditions. His severe psychiatric symptoms were successfully managed with targeted pharmacologic interventions.