Delirium may lead to poor outcomes in hospitalized older adults, and sleep deprivation may contribute to its pathogenesis. Thus, we sought to measure sleep duration and fragmentation using wrist-worn actigraphy in older, hospitalized patients with and without delirium, and to determine if actigraphy-based parameters could be used to predict delirium prior to clinical recognition. We conducted a secondary analysis of data from a recent, randomized clinical trial aimed at preventing inpatient delirium. Participants (n = 70) were aged ≥ 65 years admitted to an internal medicine service. Delirium was defined by the Confusion Assessment Method, or altered mental status identified by a clinician. Sleep measurements were actigraphy-based, and included total sleep time, median sleep bout duration and other measures of sleep fragmentation. We found that total sleep duration was similar between patients with (n = 17) and without (n = 53) delirium (mean 384.9 ± SD 162.7 versus mean 456.6 ± SD 135.8 min; p = .081). Mean sleep bout times were shorter in delirious versus never-delirious patients (median 6.1 [interquartile range 4.3-8.9] versus 7.9 [interquartile range 5.7-11.3] min, p = .048). Patients with delirium had more short sleep bouts (< 10 min) and fewer longer sleep bouts (> 30 min) compared with those without delirium. Increased sleep fragmentation was present prior to the clinical recognition of delirium. Overall, delirium was associated with increased sleep fragmentation detected by actigraphy, and sleep fragmentation might be useful as a biomarker for delirium prediction in the future.

Background: Moderate to severe pain has been frequently reported in hospitalized older adults. Pain in hospitalized persons with dementia within the context of other common symptoms, functional decline, delirium, and behavioral and psychological symptoms of dementia (BPSD), has received little attention.

Aims: Describe the incidence of pain, the pharmacologic management of pain, and the association of pain with physical function, delirium, and BPSD in hospitalized persons with dementia.

Design: Descriptive, cross-sectional study.

Setting: Six medical units in three hospitals.

Participants: Baseline data from 299 hospitalized persons with dementia enrolled in the Family-centered Function-focused Care (Fam-FFC) cluster randomized trial.

Methods: Descriptive analyses of pain used the Pain Assessment in Advanced Dementia (PAINAD) scale and the use of medication for pain management. Linear regression analyses tested relationships between pain and:1) physical function (Barthel Index), 2) delirium severity (Confusion Assessment Method Severity Short Form) and 3) BPSD severity (Neuropsychiatric Inventory- Questionnaire).

Results: The majority of the sample was female (61.9%), non-Hispanic (98%), and Black (53.2%), with a mean age of 81.58 (SD=8.54).Of the 299 patients, 166 (56%) received pain medication. Of the 108 individuals who demonstrated pain, 40% (n=43) did not receive pain medication. When controlling for age, gender, cognition, and comorbidities, pain was significantly associated with function, delirium severity, and BPSD severity.

Conclusions: Results suggest that pain may be undertreated in hospitalized persons with dementia, and should be considered upon admission to optimize function, decrease delirium, and prevent or decrease BPSD.

Background: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population.

Methods: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events.

Results: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002).

Conclusions: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Background: Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo.

Methods: In this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 μg kg^-1 h^-1) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method.

Results: POD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52-1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital.

Conclusions: Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study.

Clinical trial registration: NCT03388541.

Background and purpose: Poststroke delirium (PSD) is an independent predictor of unfavorable outcome. Despite its individual and socioeconomic burden, its frequency, clinical course, and routine detection remain unresolved. This study aimed to assess psychometric properties of established delirium screening tools and investigate the natural course of PSD.

Methods: This study investigated patients presenting with high-risk transient ischemic attacks or ischemic stroke within 24 hours during a 3-month period. Twice-daily screenings for PSD were done using the confusion assessment method, nursing delirium scale, and rapid delirium assessment, and evaluated for noninferiority against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. We investigated demographic and stroke characteristics as predictors of PSD, neurological deficits as predictors of false screening results, and conducted a simulation study to estimate the best timing to identify PSD.

Results: We enrolled 141 patients (73.8±10.4 years of age, 61 female) with a mean National Institutes of Health Stroke Scale score of 6.4±6.5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based PSD incidence was 39%, which manifested within 24 hours in 25% and 72 hours in almost all cases. The confusion assessment method was the only screening tool noninferior to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ratings providing a sensitivity of 82% and specificity of 80%. Age (odds ratio, 1.07 [1.02-1.13] per year, P=0.004) and National Institutes of Health Stroke Scale (odds ratio, 1.24 [1.15-1.34] per point, P<0.001) were predictors of PSD. False-positive screening results were associated with stroke-induced disorientation (odds ratio, 6.1 [3.2-11.61], P<0.001) and neglect (odds ratio, 2.17 [1.22-3.87], P=0.008). Simulations revealed that one in 4 cases is missed with less than daily screenings.

Conclusions: PSD is a common complication of stroke and transient ischemic attack. Detection is challenged by confounding effects such as focal neurological deficits and the necessity for at least daily screenings. Future studies are required to investigate implementation of these findings in clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03930719.

Objectives: Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery.

Design: A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019.

Setting: Tertiary academic medical center.

Participants: Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement.

Intervention: Ramelteon (8 mg) or placebo MEASUREMENTS: Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus.

Results: Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21-7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups.

Conclusion: In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium.

Background: Although many studies have reported numerous risk factors for postoperative delirium, data are scarce about preoperative anxiety as a risk factor. The study aimed to investigate the association between preoperative anxiety and postoperative delirium in older patients undergoing cardiac surgery.

Methods: Secondary data analysis of a randomized, observer-blind, controlled trial. A total of 190 patients 65 years or older and admitted to the intensive care unit and cardiac surgery unit of a university hospital scheduled for elective on-pump cardiac surgery were included. State anxiety was measured preoperatively using the Amsterdam Preoperative Anxiety and Information Scale and the Visual Analogue Scale for anxiety. Incidence of delirium was measured during the first 5 postoperative days using the Confusion Assessment Method for Intensive Care Unit (when ventilated), or the 3 Minute Diagnostic Interview for Confusion Assessment Method (when extubated) and by daily chart review.

Results: Preoperative state anxiety was reported by 31% of the patients and 41% had postoperative delirium. A multiple step logistic regression analyses revealed no association between preoperative anxiety and postoperative delirium. Significant risk factors for postoperative delirium were age (OR = 1.10, 95% CI (1.03-1.18)), activities of daily living (0.69, 95% CI (0.50-0.96)), diabetes mellitus (OR = 3.15, 95% CI (1.42-7.00)) and time on cardiopulmonary bypass (OR = 1.01, 95% CI (1.00 to 1.02)).

Conclusions: No relationship could be found between preoperative anxiety and postoperative delirium.

Background: Postoperative delirium is common in patients undergoing coronary artery bypass grafting, characterized by cognitive decline. This study aimed to evaluate the effect of early planned mobilization on delirium after coronary artery bypass grafting.

Methods: This double-blind randomized clinical trial enrolled 92 consecutive patients who underwent coronary artery bypass grafting from September to December 2018. The patients were divided into two groups of 46: a mobilization protocol was applied in the intervention group in the first 2 days after surgery; the control group received routine nursing care only. Demographic data, medical records, and Neecham confusion scores were analyzed.

Results: Patients in the control group used cigarettes (31.1% vs. 11.1%, p = 0.020) and opium poppy for recreation (35.6% vs. 8.9%, p = 0.002) more frequently, had longer intubation times (11.91 ± 3.87 vs. 10.23 ± 2.71 h, p = 0.020), and fewer blood components infused (15.6% vs. 33.3%, p = 0.05). More patients in the intervention group had normal function on the 2nd postoperative day compared to the control group (25 vs. 2, respectively, p = 0.001). The intervention group had significantly higher Neecham scores on postoperative day 2 (22.49 ± 2.03 vs. 26.82 ± 2.10, p = 0.001). Multivariable analysis showed significant associations between Neecham score and age (p = 0.022), ejection fraction (p = 0.015), myocardial infarction (p = 0.016), systolic pressure (p = 0.009), and diastolic pressure (p = 0.008).

Conclusions: Early planned mobilization was effective in reducing postoperative delirium in patients undergoing coronary artery bypass grafting.

Background: Early mobilization of patients in intensive care units (ICUs) improves patient recovery, but implementation remains challenging. Protocols may enhance the rate of out-of-bed mobilizations.

Aim: To evaluate the effect of implementing a protocol for early mobilization on the rate of out-of-bed mobilizations and other outcomes of ICU patients.

Study design: Multicentre, stepped-wedge, cluster-randomized pilot study.

Methods: After a control period, five ICUs were allocated to the implementation of an inter-professional protocol for early mobilization in a randomized, monthly order. Mobilization of ICU patients was evaluated by monthly 1-day point prevalence surveys using the ICU Mobility Scale. The primary outcome was the percentage of patients mobilized out of bed, defined as level 3 on the ICU Mobility Scale (sitting on edge of bed) or higher. Secondary outcomes were mechanical ventilation, delirium and ICU- and hospital-days, as well as unwanted safety events.

Results: Out-of-bed mobilizations increased non-significantly from 36·2% (n = 55) of 152 patients during the control period to 45·8% (n = 55) of 120 patients during the intervention period (difference 9·6%; 95% confidence interval -2·1 to 21·3%). Of 55 mobilized patients per group, more patients were mobilized once per day during the intervention period (intervention: n = 41 versus control: n = 23 patients). Multiple daily mobilizations decreased (control: n = 32 control versus intervention: n = 14 patients). Secondary outcomes, such as days with mechanical ventilation, delirium and in ICU and hospital, did not significantly differ. Adherence to the protocol was >90%; unwanted safety events were rare.

Conclusions: Implementing a protocol for early mobilization of ICU patients showed a trend towards more patients being mobilized. Without additional staff in participating ICUs, a significant increase in ICU mobilizations was not to be anticipated. More research should address whether more staff would increase the number of frequent mobilizations and if this is relevant to outcomes.

Relevance to clinical practice: Implementing inter-professional protocols for mobilization is feasible and safe and may contribute to an increase of ICU patients mobilized out of bed.

Background: Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC.

Methods: Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium.

Results: Over 16 months, 60/616 (9.7%; 95% CI: 7.5-12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9-56.1%) vs 10/30 (33%; 95% CI: 17.3-52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ² = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry.

Conclusions: A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial.

Trial registration: Registered on July 21st 2014 with ClinicalTrials.gov : NCT02200172 .