Delirium screening with 4AT in patients aged 65 years and older admitted to the Emergency Department with suspected sepsis: a prospective cohort study

Purpose We aimed to study the use of The 4 ‘A’s test (4AT), a rapid delirium screening tool, performed upon Emergency Department (ED) admission, and to characterize older patients admitted to the ED with and without sepsis in terms of delirium features. Methods In this prospective cohort study, we included patients aged ≥ 65 years, admitted to the ED with suspected sepsis. ED nurses and doctors performed delirium screening with 4AT within two hours after ED admission, and registered the time spent on the screening in each case. Sepsis and delirium during the hospital stay were diagnosed retrospectively, according to recommended diagnosis criteria. Results Out of the 196 patients included (mean age 81 years, 60% men), 100 patients fulfilled the sepsis diagnosis criteria. The mean 4AT screening time was 2.5 Minutes. In total, 114 patients (58%) had a 4AT score ≥ 1, indicating cognitive impairment, upon ED admission. Sepsis patients more often had a 4AT score ≥ 4, indicating delirium, than patients without sepsis (40% vs. 26%, p < 0.05). Out of the 100 patients with sepsis, 68 (68%) had delirium during the hospital stay, as compared to 34 out of 96 patients (35%) without sepsis (p < 0.05). Conclusion Delirium screening upon ED admission, using 4AT, was feasible among patients aged ≥ 65 years admitted with suspected sepsis. Two out of three patients had at least one feature of delirium upon admission. The prevalence of delirium during the hospital stay was high, particularly in patients with sepsis.publishedVersio

Delirium is frequently underdiagnosed among older hospitalised patients despite available information in hospital medical records

Background In-hospital delirium is associated with adverse outcomes and is underdiagnosed, limiting research and clinical follow-up. Objective To compare the incidence of in-hospital delirium determined by chart-based review of electronic medical records (D-CBR) with delirium discharge diagnoses (D-DD). Furthermore, to identify differences in symptoms, treatments and delirium triggers between D-CBR and D-DD. Method The community-based cohort included 2,115 participants in the Hordaland Health Study born between 1925 and 1927. Between 2018 and 2022, we retrospectively reviewed hospital electronic medical records from baseline (1997–99) until death prior to 2023. D-DD and D-CBR were validated using The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for delirium. Results Of the 2,115 participants, 638 had in-hospital delirium. The incidence rate (IR) of D-CBR was 29.8 [95% confidence interval 28, 32] per 1,000 person-years, whereas the IR by D-DD was 3.4 [2.8, 4.2]. The IR ratio was 9.14 (P < 0.001). Patients who received pharmacological treatment for delirium (n = 121, odds ratio (OR) 3.4, [2.1, 5.4], P < 0.001), who were affected by acute memory impairment (n = 149, OR 2.8, [1.8, 4.5], P < 0.001), or change in perception (n = 137, OR 2.9, [1.8, 4.6] P < 0.001) had higher odds for D-DD. In contrast, post-operative cases (OR 0.2, [0.1, 0.4], P < 0.001) had lower odds for D-DD. Conclusion Underdiagnosis of in-hospital delirium was a major issue in our study, especially in less severe delirium cases. Our findings emphasise the need for integrating systematic delirium diagnostics and documentation into hospital admission and discharge routines.publishedVersio

The use of clonidine in elderly patients with delirium; pharmacokinetics and hemodynamic responses

Background The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is an RCT investigating the effect of clonidine in medical patients > 65 years with delirium. To assess the dosage regimen and safety measures of this study protocol, we measured the plasma concentrations and hemodynamic effects of clonidine in the first 20 patients. Methods Patients were randomised to clonidine (n = 10) or placebo (n = 10). The treatment group was given a loading dose (75μg every 3rd hour up to a maximum of 4 doses) to reach steady state, and further 75μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days. Blood pressure (BP) and heart rate (HR) were measured just before every dose. If the systolic BP was < 100 mmHg or HR < 50 beats per minute the next dose was omitted. Plasma concentrations of clonidine were measured 3 h after each drug intake on day 1, just before intake (day 2 and at steady state day 4–6) and 3 h after intake at steady state (Cmax). Our estimated pre-specified plasma concentration target range was 0.3–0.7μg/L. Results 3 h after the first dose of 75μg clonidine, plasma concentration levels rose to median 0.35 (range 0.24–0.40)μg/L. Median trough concentration (C0) at day 2 was 0.70 (0.47–0.96)μg/L. At steady state, median C0 was 0.47 (0.36–0.76)μg/L, rising to Cmax 0.74 (0.56–0.95)μg/L 3 h post dose. A significant haemodynamic change from baseline was only found at a few time-points during the loading doses within the clonidine group. There was however extensive individual BP and HR variation in both the clonidine and placebo groups, and when comparing the change scores (delta values) between the clonidine and the placebo groups, there were no significant differences. Conclusions The plasma concentration of clonidine was at the higher end of the estimated therapeutic range. Hemodynamic changes during clonidine treatment were as expected, with trends towards lower blood pressure and heart rate in patients treated with clonidine, but with dose adjustments based on SBP this protocol appears safe. Trial registration ClinicalTrials.gov NCT01956604, 09.25.2013. EudraCT Number: 2013–000815-26, 03.18.2013. Enrolment of first participant: 04.24.2014

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-β42, amyloid-β40, 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, β = 0.85; 95% confidence interval: 0.03-1.68) and neurofilament light chain (β = 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 (β = 1.54; 95% confidence interval: 1.05-2.0) and neurofilament light chain (β = 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.</p

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial

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

The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID:a randomised placebo-controlled trial

Background Delirium affects 15% of hospitalised patients and is linked with poor outcomes, yet few pharmacological treatment options exist. One hypothesis is that delirium may in part result from exaggerated and/or prolonged stress responses. Dexmedetomidine, a parenterally-administered alpha2-adrenergic receptor agonist which attenuates sympathetic nervous system activity, shows promise as treatment in ICU delirium. Clonidine exhibits similar pharmacodynamic properties and can be administered orally. We therefore wish to explore possible effects of clonidine upon the duration and severity of delirium in general medical inpatients. Methods/Design The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is a randomised, placebo-controlled, double-blinded, parallel group study with 4-month prospective follow-up. We will recruit 100 older medical inpatients with delirium or subsyndromal delirium in the acute geriatric ward. Participants will be randomised to oral clonidine or placebo until delirium free for 2 days (Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria), or after a maximum of 7 days treatment. Assessment of haemodynamics (blood pressure, heart rate and electrocardiogram) and delirium will be performed daily until discharge or a maximum of 7 days after end of treatment. The primary endpoint is the trajectory of delirium over time (measured by Memorial Delirium Assessment Scale). Secondary endpoints include the duration of delirium, use of rescue medication for delirium, pharmacokinetics and pharmacodynamics of clonidine, cognitive function after 4 months, length of hospital stay and need for institutionalisation. Discussion LUCID will explore the efficacy and safety of clonidine for delirium in older medical inpatients. Trial registration ClinicalTrials.gov NCT01956604 . EudraCT Number: 2013-000815-2

Music Interventions and Delirium in Adults: A Systematic Literature Review and Meta-Analysis

Delirium is a neuropsychiatric syndrome represented by an acute disturbance in attention, awareness and cognition, highly prevalent in older, and critically ill patients, and associated with poor outcomes. This review synthesized existing evidence on the effectiveness of music interventions on delirium in adults, and music interventions (MIs), psychometric assessments and outcome measures used. We searched MEDLINE, PsychINFO, SCOPUS, Clinical Trials and CENTRAL for quantitative designs comparing any MIs to standard care or another intervention. From 1150 studies 12 met the inclusion criteria, and 6 were included in the meta-analysis. Narrative synthesis showed that most studies focused on prevention, few assessed delirium severity, with the majority of studies reporting beneficial effects. The summary relative risk for incident delirium comparing music vs. no music in postsurgical and critically ill older patients was 0.52 (95% confidential interval (CI): 0.20&ndash;1.35, I2 = 79.1%, heterogeneity &lt;0.0001) for the random effects model and 0.47 (95% CI: 0.34&ndash;0.66) using the fixed effects model. Music listening interventions were more commonly applied than music therapy delivered by credentialed music therapists, and delirium assessments methods were heterogeneous, including both standardized tools and systematic observations. Better designed studies are needed addressing effectiveness of MIs in specific patient subgroups, exploring the correlations between intervention-types/dosages and delirium symptoms