Risultati per: Il delirium

Introduction
Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anaesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in patients with depression. However, the role of S-ketamine in preventing POD remains unknown. Therefore, this study aims to evaluate the effect of intraoperative prophylactic S-ketamine compared with that of dexmedetomidine on the incidence of POD in elderly patients undergoing non-cardiac thoracic surgery.

Methods and analysis
This will be a randomised, double-blinded, placebo-controlled, positive-controlled, non-inferiority trial that enrolled patients aged 60–90 years undergoing thoracic surgery. The patients will be randomly allocated in a ratio of 1:1:1 to S-ketamine, dexmedetomidine or normal saline placebo groups using computer-generated randomisation with a block size of six. The primary outcome will be the incidence of POD within 4 days after surgery and this will be assessed using a 3-Minute Diagnostic Confusion Assessment Method two times per day. The severity and duration of POD, the incidence of emergence delirium, postoperative pain, quality of sleep, cognitive function, and the plasma concentrations of acetylcholine, brain-derived neurotrophic factor, tumour necrosis factor-α and incidence of adverse events will be evaluated as secondary outcomes.

Ethics and dissemination
Ethical approval has been obtained from the Institutional Review Board of the Cancer Hospital and the Institute of Guangzhou Medical University (ZN202119). At the end of the trial, we commit to making a public disclosure available, regardless of the outcome. The public disclosure will include a publication in an appropriate journal and an oral presentation at academic meetings.

Trial registration number
ChiCTR2100052750 (NCT05242692).

Introduction
Delirium is a complex condition in which altered mental state and cognition causes severe distress and poor clinical outcomes for patients and families, anxiety and stress for the health professionals and support staff providing care, and higher care costs. Hospice patients are at high risk of developing delirium, but there is significant variation in care delivery. The primary objective of this study is to demonstrate the feasibility of an implementation strategy (designed to help deliver good practice delirium guidelines), participant recruitment and data collection.

Methods and analysis
Three work packages in three hospices in the UK with public involvement in codesign, study management and stakeholder groups: (1) experience-based codesign to adapt an existing theoretically-informed implementation strategy (Creating Learning Environments for Compassionate Care (CLECC)) to implement delirium guidelines in hospices; (2) feasibility study to explore ability to collect demographic, diagnostic and delirium management data from clinical records (n=300), explanatory process data (number of staff engaged in CLECC activities and reasons for non-engagement) and cost data (staff and volunteer hours and pay-grades engaged in implementation activities) and (3) realist process evaluation to assess the acceptability and flexibility of the implementation strategy (preimplementation and postimplementation surveys with hospice staff and management, n=30 at each time point; interviews with hospice staff and management, n=15). Descriptive statistics, rapid thematic analysis and a realist logic of analysis will be used be used to analyse quantitative and qualitative data, as appropriate.

Ethics and dissemination
Ethical approval obtained: Hull York Medical School Ethics Committee (Ref 21/23), Health Research Authority Research Ethics Committee Wales REC7 (Ref 21/WA/0180) and Health Research Authority Confidentiality Advisory Group (Ref 21/CAG/0071). Written informed consent will be obtained from interview participants. A results paper will be submitted to an open access peer-reviewed journal and a lay summary shared with study site staff and stakeholders.

Trial registration number
ISRCTN55416525.

Objective
To internally and externally validate a delirium predictive model for adult patients admitted to intensive care units (ICUs) following surgery.

Design
A prospective, observational, multicentre study.

Setting
Three university-affiliated teaching hospitals in Thailand.

Participants
Adults aged over 18 years were enrolled if they were admitted to a surgical ICU (SICU) and had the surgery within 7 days before SICU admission.

Main outcome measures
Postoperative delirium was assessed using the Thai version of the Confusion Assessment Method for the ICU. The assessments commenced on the first day after the patient’s operation and continued for 7 days, or until either discharge from the ICU or the death of the patient. Validation was performed of the previously developed delirium predictive model: age+(5xSOFA)+(15xbenzodiazepine use)+(20xDM)+(20xmechanical ventilation)+(20xmodified IQCODE >3.42).

Results
In all, 380 SICU patients were recruited. Internal validation on 150 patients with the mean age of 75±7.5 years resulted in an area under a receiver operating characteristic curve (AUROC) of 0.76 (0.683 to 0.837). External validation on 230 patients with the mean age of 57±17.3 years resulted in an AUROC of 0.85 (0.789 to 0.906). The AUROC of all validation cohorts was 0.83 (0.785 to 0.872). The optimum cut-off value to discriminate between a high and low probability of postoperative delirium in SICU patients was 115. This cut-off offered the highest value for Youden’s index (0.50), the best AUROC, and the optimum values for sensitivity (78.9%) and specificity (70.9%).

Conclusions
The model developed by the previous study was able to predict the occurrence of postoperative delirium in critically ill surgical patients admitted to SICUs.

Trial registration number
Thai Clinical Trail Registry (TCTR20180105001).

Introduction
Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status.

Methods and analysis
This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.
Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery.

Ethics and dissemination
This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.

Trial registration number
NCT05029050.

Introduction
Postoperative delirium is a frequent adverse event following elective non-cardiac surgery. The occurrence of delirium increases the risk of functional impairment, placement to facilities other than home after discharge, cognitive impairment at discharge, as well as in-hospital and possibly long-term mortality. Unfortunately, there is a dearth of effective strategies to minimise the risk from modifiable risk factors, including postoperative pain control and the analgesic regimen. Use of potent opioids, currently the backbone of postoperative pain control, alters cognition and has been associated with an increased risk of postoperative delirium. Literature supports the intraoperative use of lidocaine infusions to decrease postoperative opioid requirements, however, whether the use of postoperative lidocaine infusions is associated with lower opioid requirements and subsequently a reduction in postoperative delirium has not been investigated.

Methods and analysis
The Lidocaine Infusion for the Management of Postoperative Pain and Delirium trial is a randomised, double-blinded study of a postoperative 48-hour infusion of lidocaine at 1.33 mg/kg/hour versus placebo in older patients undergoing major reconstructive spinal surgery at the University of California, San Francisco. Our primary outcome is incident delirium measured daily by the Confusion Assessment Method in the first three postoperative days. Secondary outcomes include delirium severity, changes in cognition, pain scores, opioid use, incidence of opioid related side effects and functional benefits including time to discharge and improved recovery from surgery. Lidocaine safety will be assessed with daily screening questionnaires and lidocaine plasma levels.

Ethics and dissemination
This study protocol has been approved by the ethics board at the University of California, San Francisco. The results of this study will be published in a peer-review journal and presented at national conferences as poster or oral presentations. Participants wishing to know the results of this study will be contacted directly on data publication.

Trial registration number
NCT05010148.

Stroke, Volume 53, Issue Suppl_1, Page ATMP57-ATMP57, February 1, 2022. Background:Post-stroke delirium (PSD) is associated with increased mortality and worse long-term functional outcomes. Patients who receive reperfusion therapies in the hospital are frequently kept from regular sleep-wake cycles the first 24 hrs after treatment, and this disruption could lead to an increase in PSD. In this study, we evaluate the effect of PSD on immediate and long-term outcomes in AIS patients receiving reperfusion therapies.Methods:Between September 2019 and June 2021, pts diagnosed with AIS within 48 hrs of stroke onset were prospectively evaluated for PSD using the Confusion Assessment Method (CAM)-ICU daily for the first eight days of their hospital stay. Patients with severe stroke and expected mortality within the first month at the time of admission or with severe aphasia unable to follow commands were excluded. Reperfusion therapies were defined as any IV thrombolytic, IA thrombolytic, or mechanical thrombectomy (MT). The primary outcome was considered a 90-day mRS score of 0-2.Results:Of 179 patients assessed with the CAM-ICU, 89 (49.7%) had PSD. We identified 94 patients that had undergone one or both reperfusion therapies; 52 (55.3%) had delirium. Patients who received tPa had a higher risk for delirium (42 vs 29, p = 0.04), but no difference was observed with MT (Table 1). Patients with PSD had a longer hospital length of stay and a higher median admission NIHSS. Patients with delirium who received tPA were more likely to be discharged to inpatient rehabilitation facilities than home (p-value 0.004, OR 10.1 95%CI 2.1,48). No significant difference was found in 90-day modified ranking scale (mRS) scores of 0-2 in those with or without PSD.Conclusion:AIS patients with PSD after reperfusion therapy had no significant difference in 90-day good outcomes despite having longer hospital admissions and being less likely to be discharged home. Further evaluation into how reperfusion therapies convey protection to patients is necessary.

Stroke, Volume 53, Issue Suppl_1, Page AWP138-AWP138, February 1, 2022. Background:Delirium in-hospital (DIH) results in poor in-patient outcomes. However, it’s longer-term effects among intracerebral hemorrhage (ICH) patients are not well characterized. We sought to evaluate the association between DIH and 90-day readmission (RA) among primary ICH patients.Method:Clinical, imaging and outcomes data, from May 2016 to June 2021, were obtained from theNeurological Outcomes Registry for ICH (NEURO-RICH); an informatics pipeline across 7 comprehensive and primary stroke centers which implement protocolized delirium assessments via 4AT / CAM-ICU scales. Demographic (age, sex, race, ethnicity, marital status), Glasgow Coma Scale (GCS), systolic and diastolic blood pressure (S/DBP), sepsis, systemic inflammatory response syndrome, and comorbidity data were analyzed. Survival analysis for time-to-90-Day RA was performed with death modeled as a competing risk. Sub hazard ratios (SHR) and 95% confidence intervals (CI) are reported. Subgroup with imaging data (ICH score and cerebral small vessel disease) was analyzed.Results:Final analyses included 1,434 ICH patients (mean age: 66.0 years, 47.2% female, 24.8% non-Hispanic Black, 19.9% Hispanic, median GCS: 13.2, SBP: 163 mmHg). In the fully adjusted model, DIH was significantly associated with higher rates of 90-Day RA (SHR, CI: 2.24, 1.04 – 4.81) (Figure 1A). Anticoagulant therapy (1.36, 1.03 – 1.80), hypertension (1.95, 1.38 – 2.74), diabetes (1.13, 1.09 – 1.17), and Charlson Comorbidity Index (1.08, 1.04 – 1.13) were also independently associated with 90-Day RA (SHR, CI reported). In the imaging subgroup of 523 patients, DIH retained independent association with 90-Day RA (SHR: 3.94 [1.37 – 11.36]) (Figure 1B).Discussion:In addition to traditional predictors of poor outcomes among ICH patients, DIH demonstrated strong and independent association with 90-day RA. Screening, identification, and active management of DIH is critical to reduce long-term disease burden of ICH.

Stroke, Volume 53, Issue Suppl_1, Page AWP118-AWP118, February 1, 2022. Background:Delirium after acute ischemic stroke is a common clinical occurrence, associated with longer hospital admissions, worse functional outcomes, and increased mortality. We aim in a prospective study to assess the characteristics and risk factors for delirium after acute ischemic stroke (AIS) in a US population.Methods:Between September 2019 and June 2021, patients diagnosed with AIS within 48 hrs of stroke onset were prospectively evaluated for delirium using the Confusion Assessment Method (CAM)-ICU daily for the first eight days of their hospital stay. Patients with severe stroke and expected mortality within the first month at the time of admission or with severe aphasia unable to follow commands were excluded. Data regarding demographics, co-morbidities, hospital stay, stroke metrics, lab work, and medications were analyzed.Results:Over 12 non-consecutive months (due to pandemic interruptions), we evaluated 213 patients, of which 179 could be assessed with the CAM-ICU. Delirium was present in 89 (49.7%), occurring within the first 24 hours of admission in 33.6% and for longer than one day in 32.0%. There were no statistically significant differences in age, gender, race, co-morbidities, or TOAST etiology among patients with and without delirium (Table 1). Patients with delirium had higher NIHSS and were more likely to receive tPA. Patients with delirium were more likely to be discharged to inpatient rehabilitation facilities than home (p=0.05). Only patients with delirium had unexpected mortality after admission, but this statistic failed to show significance.Conclusion:In a cohort of AIS patients without significant expected mortality on admission, the incidence of delirium is high. Our study confirms prior results demonstrating higher inpatient mortality, longer hospital admissions among patients with delirium, and more delirium in patients receiving tPA.

Stroke, Volume 53, Issue Suppl_1, Page ATP117-ATP117, February 1, 2022. Introduction:Stroke patients who develop delirium after their stroke can have worse cognitive and functional outcomes. Prior studies suggest that admission Neutrophil Lymphocyte ratio (NLR) is associated with the development of delirium in both ischemic (AIS) and hemorrhagic stroke geriatric patients. In this study we examine AIS patients for laboratory predictors of delirium.Methods:Between September 2019 and June 2021, patients diagnosed with AIS, within 48 hrs of last seen normal or time of onset and had expected mortality >1 month were prospectively evaluated for delirium using the Confusion Assessment Method (CAM)-ICU daily for the first 8 days of their hospital stay and at discharge. NLR ratio was derived from patients’ admission blood panel and were both evaluated as continuous variables and in quartiles.Results:During the study period, 213 patients were screened for delirium. Of these, 18 patients could not be evaluated by the CAM-ICU at any point during the first eight days and 99(50.5%) screened positive for delirium. Our patient population was younger and had higher rates of endovascular and thrombolytic therapy than prior studies. Similar to other studies, patients with delirium had more severe NIHSS score (Table 1), longer lengths of stay, were more likely to be discharged to inpatient rehab than home, and trended to higher inpatient mortality. However, there was no apparent association between NLR and the development of delirium.Conclusion:In our patient population of younger patients who were more likely to receive reperfusion therapies, we did not find that NLR is associated with delirium. These results warrant additional study, specifically if reperfusion therapies such as thrombectomy and thrombolysis change how the nature of delirium and its predictive variables.

Stroke, Volume 53, Issue Suppl_1, Page A92-A92, February 1, 2022. Background:Delirium in-hospital (DIH) is common among the critically ill. However, DIH incidence and outcomes are not well characterized among ischemic stroke (IS) patients, particularly those treated with intravenous tissue plasminogen activator (tPA) and / or mechanical thrombectomy (MT).Methods:Utilizing data from a healthcare system with standardized delirium screening protocols, DIH was determined by a positive 4AT / CAM-ICU screen or diagnosis codes. IS patients with tPA or MT were flagged and a subset with available 90-day modified Rankin Scale (mRS) were analyzed for shifts in mRS scores associated with DIH, via ordinal logistic regression models adjusted for age, stroke severity, tPA or MT, Charlson Comorbidity Index [CCI], prior stroke and sepsis / infections. Common odds ratios (OR) and 95% confidence intervals (CI) are reported.Results:Between May 2016 and June 2021, IS was the primary discharge diagnosis in 12,415 encounters (10,878 unique patients). DIH was documented in 41.6% of IS encounters, compared to 20.0% of non-IS encounters. Stroke-DIH patients (vs no-DIH Stroke) were older (median: 75 vs 65 years), more frequently female (53.3% vs 48.7%), with higher comorbidity burden (median CCI: 7 vs 5), longer hospital stays (median: 6 vs 3 days), higher in-hospital mortality (3.1% vs 0.5%), and fewer home discharges (36.2% vs 75.2%). Among a sub-cohort of 2,785 IS patients with 90-day mRS, fully adjusted model indicated lower mRS (OR, CI: 0.48, 0.41-0.57) for those with tPA or MT, and worse outcomes for DIH patients (OR, CI: 2.70, 2.26-3.23). Among 948 treated IS patients, DIH remained a significant risk for worse outcomes (OR, CI: 2.54, 1.89-3.43).Conclusion:Delirium was twice as common in IS patients and was a negative prognostic indicator of short and long-term outcomes among non-treated and treated IS patients. Active screening and management of DIH is critically important to improve stroke outcomes.

Stroke, Volume 53, Issue Suppl_1, Page ATMP58-ATMP58, February 1, 2022. Background:Delirium is an acute cognitive disturbance frequently characterized by abnormal levels of motor activity and sleep-wake cycle disruption. However, the degree to which delirium affects activity patterns in the acute period after stroke is unclear. We aimed to examine these patterns in a cohort of patients with intracerebral hemorrhage (ICH).Methods:We enrolled 40 patients with supratentorial ICH and hemiparesis who had daily delirium assessments performed by expert clinicians. Continuous measurements of activity were captured using bilateral wrist actigraphs for the duration of each patient’s admission. Activity data were collected in 1-minute intervals, with “rest” intervals defined as periods with zero activity recorded. We compared differences in activity based on delirium status across multiple time intervals using linear regression models adjusted for age, ICH severity, and mechanical ventilation.Results:There were 312 total days of actigraphy monitoring, of which 233 (75%) were rated as days with delirium; 85% of patients (34/40) experienced delirium during their hospitalization. In multivariable analyses, delirium days were associated with 66.3 (95% CI 9.4-123.2) fewer total minutes of rest, including 6.1% (95% CI 2.3-9.9%) fewer minutes of rest during daytime periods (06:00-21:59) and 9.2% (95% CI 3.3-15.0%) fewer minutes of rest during nocturnal periods (22:00-5:59). In separate analyses for individual hourly intervals, delirium days were associated with significantly higher levels of activity across multiple consecutive time intervals, including 05:00-09:00 and 17:00-03:00. In subgroup analyses, hyperactive or mixed delirium was associated with fewer total daily minutes of rest compared to hypoactive delirium, along with lower proportions of time at rest during both daytime and nocturnal periods (4.3% [95% CI 0.5-8.0%] and 6.5% [95% CI 0.9-12.1%] lower, respectively).Conclusion:Post-stroke delirium is associated with less rest and higher overall levels of activity, especially during nocturnal periods and in patients with hyperactive or mixed delirium.

Stroke, Volume 53, Issue Suppl_1, Page AWP116-AWP116, February 1, 2022. Background:Delirium occurs frequently in patients with stroke but is often underrecognized. We aimed to develop a novel delirium screening tool designed specifically for stroke patients, and to test its feasibility and accuracy in a pilot study.Methods:We designed an easy-to-use 5-point instrument called the Fluctuating Mental Status Evaluation (FMSE) and tested it in a cohort of patients with intracerebral hemorrhage (ICH) who had daily delirium assessments throughout their admission. Expert ratings were performed by an attending neurointensivist or behavioral neurologist each afternoon using DSM-5 criteria, and were derived from bedside assessments and clinical data from the preceding 24 hours. Paired FMSE assessments were performed by patients’ clinical nurses after brief training on the use of the tool. Nursing assessments were aggregated over 24-hour periods (including day and night shifts), and accuracy of the FMSE was analyzed on both a per-assessment day and per-patient basis.Results:Among the 40 enrolled patients (mean age 71.1±12.2, median initial NIHSS score 16.5 [IQR 12-20]), 34 experienced delirium during their hospitalization. There were 306 total coma-free days with paired assessments, of which 208 (68%) were rated as days with delirium. Compared to expert ratings, an FMSE score ≥1 had 86% sensitivity and 74% specificity on a per-day basis, while a score ≥2 had 68% sensitivity and 83% specificity. On a per-patient basis, a score ≥1 at any point during admission had 97% sensitivity and 67% specificity in identifying patients who experienced delirium, while a score ≥2 had 94% sensitivity and 67% specificity.Conclusion:The FMSE is a feasible delirium screening tool in ICH patients, with high real-world sensitivity and specificity. Based on these results, we plan to validate the tool in a larger, more diverse cohort of stroke patients, using score cutoffs of ≥1 as “possible” delirium and ≥2 as “probable” delirium.

Stroke, Ahead of Print. Background and Purpose:Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal.Methods:Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures.Results:Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN.Conclusions:Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders.

Stroke, Volume 53, Issue 2, Page 505-513, February 1, 2022. Background and Purpose:Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site.Methods:We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4–6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site.Results:Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3–16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8–5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17–0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7–5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2–4.3]).Conclusions:Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.