Incidence of Adverse Events Using Flumazenil in Patients With Iatrogenic Benzodiazepine Delirium: A Retrospective Study.

BACKGROUND: Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures. STUDY QUESTION: What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium? STUDY DESIGN: This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated. MEASURES AND OUTCOMES: The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status. RESULTS: A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77). CONCLUSIONS: Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.

From Traditional Typing to Intelligent Insights: A Narrative Review of Directions Toward Targeted Therapies in Delirium.

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested.

Capturing the ghost in the machine: a process for development and validation of measures of phenomenal consciousness in delirium.

BACKGROUND: Delirium has conventionally been considered a disorder of consciousness. Alertness and arousal are used as surrogates in clinical practice but are insufficient for the purposes of a more dimensional assessment of consciousness. We present a process of development and validation of candidate measures of phenomenal consciousness that could be applied to the diagnosis of delirium. METHODS: First, a narrative review of available instruments in the fields of phenomenal consciousness, including prereflective consciousness, the phenomenal-sensed experience and reflective thought, was undertaken. Eligibility of tools in the context of applicability to delirium was based upon objectivity in test interpretation and the requirement for tester administration. Second, where there was a gap in suitable cognitive tools, new items were derived using the silent generation technique. A process of face and construct validity using a diverse panel of experts was performed, and readability was evaluated. RESULTS: 814 articles were screened from the literature review. Fourteen candidate tools were reported from the three domains of phenomenal consciousness. One of these met the eligibility criteria for a delirium assessment. Fifty-seven new tests of phenomenal consciousness were identified. After a process of item reduction, a total of 26 individual tests were identified. After content validity, 22 of the 26 items were retained. The scale average content validity index was 0.89. The agreement between raters was between 80% and 97%. 100% of responses for face validity were rated as positive. Flesch Reading Ease Score was 91.6 (very easy to read). CONCLUSIONS: Candidate measures of phenomenal consciousness are described, and early validity studies are promising.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Association of Hyperoxia During Cardiopulmonary Bypass and Postoperative Delirium in the Pediatric Cardiac ICU.

OBJECTIVE: ICU delirium commonly complicates critical illness associated with factors such as cardiopulmonary bypass (CPB) time and the requirement of mechanical ventilation (MV). Recent reports associate hyperoxia with poorer outcomes in critically ill children. This study sought to determine whether hyperoxia on CPB in pediatric patients was associated with a higher prevalence of postoperative delirium. DESIGN: Secondary analysis of data obtained from a prospective cohort study. SETTING: Twenty-two-bed pediatric cardiac ICU in a tertiary children's hospital. PATIENTS: All patients (18 yr old or older) admitted post-CPB, with documented delirium assessment scores using the Preschool/Pediatric Confusion Assessment Method for the ICU and who were enrolled in the Precision Medicine in Pediatric Cardiology Cohort from February 2021 to November 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 148 patients, who underwent cardiac surgery, 35 had delirium within the first 72 hours (24%). There was no association between hyperoxia on CPB and postoperative delirium for all definitions of hyperoxia, including hyperoxic area under the curve above 5 predetermined Pao2 levels: 150 mm Hg (odds ratio [95% CI]: 1.176 [0.605-2.286], p = 0.633); 175 mm Hg (OR 1.177 [95% CI, 0.668-2.075], p = 0.572); 200 mm Hg (OR 1.235 [95% CI, 0.752-2.026], p = 0.405); 250 mm Hg (OR 1.204 [95% CI, 0.859-1.688], p = 0.281), 300 mm Hg (OR 1.178 [95% CI, 0.918-1.511], p = 0.199). In an additional exploratory analysis, comparing patients with delirium within 72 hours versus those without, only the z score for weight differed (mean [sd]: 0.09 [1.41] vs. -0.48 [1.82], p < 0.05). When comparing patients who developed delirium at any point during their ICU stay (n = 45, 30%), MV days, severity of illness (Pediatric Index of Mortality 3 Score) score, CPB time, and z score for weight were associated with delirium (p < 0.05). CONCLUSIONS: Postoperative delirium (72 hr from CPB) occurred in 24% of pediatric patients. Hyperoxia, defined in multiple ways, was not associated with delirium. On exploratory analysis, nutritional status (z score for weight) may be a significant factor in delirium risk. Further delineation of risk factors for postoperative delirium versus ICU delirium warrants additional study.

A prospective multi-center study quantifying visual inattention in delirium using generative models of the visual processing stream.

The visual attentional deficits in delirium are poorly characterized. Studies have highlighted neuro-anatomical abnormalities in the visual processing stream but fail at quantifying these abnormalities at a functional level. To identify these deficits, we undertook a multi-center eye-tracking study where we recorded 210 sessions from 42 patients using a novel eye-tracking system that was made specifically for free-viewing in the (ICU); each session lasted 10 min and was labeled with the delirium status of the patient using the Confusion Assessment Method in ICU (CAM-ICU). To analyze this data, we formulate the task of visual attention as a hierarchical generative process that yields a probabilistic distribution of the location of the next fixation. This distribution can then be compared to the measured patient fixation producing a correctness score which is tallied compared across delirium status. This analysis demonstrated that the visual processing system of patients suffering from delirium is functionally restricted to a statistically significant degree. This is the first study to explore the potential mechanisms underpinning visual inattention in delirium and suggests a new target of future research into a disease process that affects one in four hospitalized patients with severe short and long-term consequences.

Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial.

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Short-term inhalation of xenon during anesthesia for prevention of postoperative delirium in elderly patients undergoing laparoscopic radical colectomy: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. METHODS/DESIGN: This is a prospective, randomized, controlled trial and 132 patients aged 65-80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. DISCUSSION: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Differences of anticholinergic drug burden between older hospitalized patients with and without delirium: a systematic review and meta-analysis based on prospective cohort studies.

OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].

Trace of delirium after robotic lower abdominal tumor resection at different end-tidal carbon dioxide: a RCT trial.

BACKGROUND: Postoperative delirium (POD) often occurs in oncology patients, further increasing the medical and financial burden. Robotic technology in lower abdominal tumors resection reduces surgical trauma but increases risks such as carbon dioxide (CO2) absorption. This study aimed to investigate the differences in their occurrence of POD at different end-tidal CO2 levels. METHOD: This study was approved by the Ethics Committee of Affiliated Hospital of He Bei University (HDFY-LL-2022-169). The study was registered with the Chinese Clinical Trials Registry on URL: http://www.chictr.org.cn , Registry Number: ChiCTR2200056019 (Registry Date: 27/08/2022). In patients scheduled robotic lower abdominal tumor resection from September 1, 2022 to December 31, 2022, a comprehensive delirium assessment was performed three days postoperatively using the CAM scale with clinical review records. Intraoperative administration of different etCO2 was performed depending on the randomized grouping after intubation. Group L received lower level etCO2 management (31-40mmHg), and Group H maintained the higher level(41-50mmHg) during pneumoperitoneum. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regression. Preoperative mental status score, alcohol impairment score, nicotine dependence score, history of hypertension and diabetes, duration of surgery and worst pain score were included in the regression model along with basic patient information for covariate correction analysis. RESULTS: Among the 103 enrolled patients, 19 (18.4%) developed postoperative delirium. The incidence of delirium in different etCO2 groups was 21.6% in Group L and 15.4% in Group H, respectively, with no statistical differences. In adjusted multivariate analysis, age and during of surgery were statistically significant predictors of postoperative delirium. The breath-hold test was significantly lower postoperatively, but no statistical differences were found between two groups. CONCLUSION: With robotic assistant, the incidence of postoperative delirium in patients undergoing lower abdominal tumor resection was not modified by different end-tidal carbon dioxide management, however, age and duration of surgery were positively associated risk factors.

Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization's global pharmacovigilance database.

BACKGROUND: Psychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults. METHODS: Using the World Health Organization's VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65-74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia. RESULTS: Our main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01-4.96]), SNRIs (1.25 [1.07-1.46]), MAOIs (1.72 [1.41-2.09]), and the "other antidepressants" class (1.47 [1.30-1.65]). CONCLUSIONS: There was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.

Digital education about delirium for health care professional students: a mixed methods systematic review.

BACKGROUND: Competence in delirium care begins with pre-registration education for health care professionals. Although a common complication for hospitalised patients, delirium is avoidable and reversible. Delirium requires early recognition in person-centred care. Students need to learn how to identify and effectively care for 'at risk' patients. AIM: To identify and examine literature on how pre-registration health care professional students are prepared to recognise, assess, and deliver interventions to prevent delirium in practice, using digital/web based educational interventions. METHOD: Mixed methods systematic review with narrative synthesis. A protocol was registered with PROSPERO. The review questions and search strategy were guided by the Population, Phenomena of Interest, Context (PICo) framework. The PRISMA framework guided the screening, data extraction and analysis. Database searches (MEDLINE, Web of Science, Embase, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO & Scopus) were undertaken in April 2023 for publications from 2012 to 2023. Covidence software [30] was used to extract and manage the data. Quality appraisal was guided by the Crowe Critical Appraisal Tool (CCAT) [31]. FINDINGS: Ten papers were included: mixed methods (2), qualitative (1) and quantitative (7). Medical students were the most studied group (n = 5), followed by student nurses (n = 4) and mixed nursing and medical students (n = 1). Length of learning experience varied from 12 min virtual reality (VR) to a two-week 'geriatrics' elective. Learning was enhanced by player autonomy, engagement, safety, applicability, choices, multiple perspectives and moral reasoning opportunities. DISCUSSION: Digital programmes should be visually appealing, interactive with opportunities for practice and timely appropriate feedback.

Association of blood glucose change with postoperative delirium after coronary artery bypass grafting in patients with diabetes mellitus: a study of the MIMIC-IV database.

Aim: Study results on blood glucose and the risk of delirium in patients receiving cardiac surgery are inconsistent, and there is also a gap in how to manage blood glucose after coronary artery bypass grafting (CABG). This study focused on patients with diabetes mellitus (DM) undergoing CABG and explored the associations of different blood glucose-related indexes and blood glucose change trajectory with postoperative delirium (POD), with the aim of providing some information for the management of blood glucose in this population. Methods: Data of patients with DM undergoing CABG were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database in this retrospective cohort study. The blood glucose-related indexes included baseline blood glucose, mean blood glucose (MBG), mean absolute glucose (MAG), mean amplitude of glycemic excursions (MAGE), glycemic lability index (GLI), and largest amplitude of glycemic excursions (LAGE). The MBG trajectory was classified using the latent growth mixture modeling (LGMM) method. Univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the associations of blood glucose-related indexes and MBG trajectory with POD. These relationships were also assessed in subgroups of age, gender, race, estimated glomerular filtration rate (eGFR), international normalized ratio (INR), sepsis, mechanical ventilation use, and vasopressor use. In addition, the potential interaction effect between blood glucose and hepatorenal function on POD was investigated. The evaluation indexes were odds ratios (ORs), relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and 95% confidence intervals (CIs). Results: Among the eligible 1,951 patients, 180 had POD. After adjusting for covariates, higher levels of MBG (OR = 3.703, 95% CI: 1.743-7.870), MAG >0.77 mmol/L/h (OR = 1.754, 95% CI: 1.235-2.490), and GLI >2.6 (mmol/L)2/h/per se (OR = 1.458, 95% CI: 1.033-2.058) were associated with higher odds of POD. The positive associations of MBG, MAG, and GLI with POD were observed in patients aged <65 years old, male patients, White patients, those with eGFR <60 and INR <1.5, patients with sepsis, and those who received mechanical ventilation and vasopressors (all p < 0.05). Patients with class 3 (OR = 3.465, 95% CI: 1.122-10.696) and class 4 (OR = 3.864, 95% CI: 2.083-7.170) MBG trajectory seemed to have higher odds of POD, compared to those with a class 1 MBG trajectory. Moreover, MAG (RERI = 0.71, 95% CI: 0.14-1.27, AP = 0.71, 95% CI: 0.12-1.19) and GLI (RERI = 0.78, 95% CI: 0.19-1.39, AP = 0.69, 95% CI: 0.16-1.12) both had a potential synergistic effect with INR on POD. Conclusion: Focusing on levels of MBG, MAG, GLI, and MBG trajectory may be more beneficial to assess the potential risk of POD than the blood glucose level upon ICU admission in patients with DM undergoing CABG.

The interrelationship between multiple long-term conditions (MLTC) and delirium: a scoping review.

INTRODUCTION: Delirium and multiple long-term conditions (MLTC) share numerous risk factors and have been shown individually to be associated with adverse outcomes following hospitalisation. However, the extent to which these common ageing syndromes have been studied together is unknown. This scoping review aims to summarise our knowledge to date on the interrelationship between MLTC and delirium. METHODS: Searches including terms for delirium and MLTC in adult human participants were performed in PubMed, EMBASE, Medline, Psycinfo and CINAHL. Descriptive analysis was used to summarise findings, structured according to Synthesis Without Meta-analysis reporting guidelines. RESULTS: After removing duplicates, 5256 abstracts were screened for eligibility, with 313 full-texts sought along with 17 additional full-texts from references in review articles. In total, 140 met inclusion criteria and were included in the final review. Much of the literature explored MLTC as a risk factor for delirium (n = 125). Fewer studies explored the impact of MLTC on delirium presentation (n = 5), duration (n = 3) or outcomes (n = 6) and no studies explored how MLTC impacts the treatment of delirium or whether having delirium increases risk of developing MLTC. The most frequently used measures of MLTC and delirium were the Charlson Comorbidity Index (n = 98/140) and Confusion Assessment Method (n = 81/140), respectively. CONCLUSION: Existing literature largely evaluates MLTC as a risk factor for delirium. Major knowledge gaps identified include the impact of MLTC on delirium treatment and the effect of delirium on MLTC trajectories. Current research in this field is limited by significant heterogeneity in defining both MLTC and delirium.

Epigenetic signals associated with delirium replicated across four independent cohorts.

Delirium is risky and indicates poor outcomes for patients. Therefore, it is crucial to create an effective delirium detection method. However, the epigenetic pathophysiology of delirium remains largely unknown. We aimed to discover reliable and replicable epigenetic (DNA methylation: DNAm) markers that are associated with delirium including post-operative delirium (POD) in blood obtained from patients among four independent cohorts. Blood DNA from four independent cohorts (two inpatient cohorts and two surgery cohorts; 16 to 88 patients each) were analyzed using the Illumina EPIC array platform for genome-wide DNAm analysis. We examined DNAm differences in blood between patients with and without delirium including POD. When we compared top CpG sites previously identified from the initial inpatient cohort with three additional cohorts (one inpatient and two surgery cohorts), 11 of the top 13 CpG sites showed statistically significant differences in DNAm values between the delirium group and non-delirium group in the same directions as found in the initial cohort. This study demonstrated the potential value of epigenetic biomarkers as future diagnostic tools. Furthermore, our findings provide additional evidence of the potential role of epigenetics in the pathophysiology of delirium including POD.

In-Hospital Delirium and Disability and Cognitive Impairment After COVID-19 Hospitalization.

Importance: Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization. Objective: To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19. Design, Setting, and Participants: This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024. Exposure: Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU. Main Outcomes and Measures: Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score <22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome. Results: The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization. Conclusions and Relevance: In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.

Hospital-associated complications in frail older adults.

As the Japanese population continues to age steadily, the number of older adults requiring healthcare has increased. Evidence demonstrates that hospitalization for acute care has a negative impact on the health outcomes of older adults. Frail older adults tend to have multifactorial conditions collectively known as "geriatric syndromes." When those with these premorbid conditions are hospitalized for acute care, they tend to develop new problems such as delirium and new functional impairments. Adverse consequences of hospitalization include the risk of loss of functional independence and chronic disability. In 2019, the new concept of "hospital-associated complications" (HACs) was proposed to describe these new problems. HACs comprise five conditions: hospital-associated falls, delirium, functional decline, incontinence, and pressure injuries. This review discusses the important issues of HACs in relation to their classification, prevalence, risk factors, prevention, and management in older adults hospitalized for acute care. Robust prevention and management are imperative to address the serious consequences and escalating medical costs associated with HACs, and a multidimensional and multidisciplinary approach is key to achieving this goal. Comprehensive geriatric assessment (CGA) is the cornerstone of geriatric medicine and offers a holistic approach involving multidisciplinary and multidimensional assessments. Considerable evidence is accumulating regarding how CGA and coordinated care can improve the prognosis of hospitalized older adults. Further research is needed to understand the occurrence of HACs in this population and to develop effective preventive measures.

Association between preoperative persistent hyperglycemia and postoperative delirium in geriatric hip fracture patients.

BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.

Challenges in Assessment and Management of Postoperative Agitation and Delirium in a Stroke Patient with Limited English Proficiency: Case Report.

While Title VI of the Civil Rights Act of 1964 mandates use of interpreters for patients with limited English proficiency, significant disparities persist in intensive postsurgical care. We present the case of a 60-year-old Vietnamese-speaking man with a Type A aortic dissection requiring postoperative mechanical ventilation and stroke care. Despite use of a remote video interpreter, our language-discordant nursing and physician providers faced challenges in managing agitation and delirium and assessing neurological function. This case highlights the need for adequate interpretation equipment, linguistic diversity among providers, and interventions to promote and enable consistent certified and professional medical interpreter use.