Recipe for primary prevention of delirium in hospitalized older patients.

Delirium is an acute fluctuating syndrome characterized by a change in consciousness, perception, orientation, cognition, sleep-wake rhythm, psychomotor skills, and the mood and feelings of a patient. Delirium and delirium prevention remain a challenge for healthcare professionals, especially nurses who form the basis of patient care. It also causes distress for patients, their caregivers and healthcare professionals. However, delirium is preventable in 30-40% of cases. The aim of this article is to summarize the delirium risk models, delirium screening tools, and (non-pharmacological) delirium prevention strategies. A literature search of review articles supplemented by original articles published in PubMed, Cinahl, and Cochrane between 1 January 2000 and 31 December 2020 was carried out. Among the older patients, delirium is a common condition with major consequences in terms of mortality and morbidity, but prevention is possible. Despite the fact that delirium risk models, delirium screening scales and non-pharmacological prevention are available for the development of a hospital delirium prevention programme, such a programme is still not commonly used on a daily basis.

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study.

BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. METHODS: The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer's Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid ß and tau in cerebrospinal fluid/blood and neurophysiological measures. DISCUSSION: The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. TRIAL REGISTRATION: Nederlands Trial Register NTR5867 . Registered 20 May 2016.

Mortality associated with delirium after hip-surgery: a 2-year follow-up study.

BACKGROUND: delirium after hip-surgery is associated with poor outcome. Few studies examined the mortality risk associated with delirium in elderly hip-surgery patients after 1 year or more. Aim of this study was to examine the hazard risk associated with delirium in elderly hip-surgery patients at 2-year follow-up, controlling for baseline risk factors and interaction effects. METHODS: this is a secondary analysis based on data from a controlled clinical trial evaluating efficacy of haloperidol prophylaxis for delirium conducted in a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Randomised and non-randomised patients (n = 603) were followed-up for 2 years. Predefined risk factors and other potential risk factors for delirium were assessed prior to surgery. Primary outcome was time of death during the follow-up period. Cox proportional hazards were estimated and compared across patients who had postoperative delirium during hospitalisation and those who did not. RESULTS: a total of 90/603 patients (14.9%) died during the study period and 74/603 (12.3%) had postoperative delirium. Incidence of delirium was higher in patients who died (32.2%) compared with those who survived (8.8%). The interaction effect of delirium by illness severity on mortality was significant after adjusting for predefined delirium risk factors and other potential covariates including study intervention (adjusted Hazard risk = 1.05, 95% CI 1.02-1.08). A total of 14/27 delirium patients who were severely ill on admission died during follow-up versus 15/47 delirium patients who were not (RR 1.63 CI 0.93-2.83). CONCLUSIONS: delirium does not independently predict mortality at 2-year follow-up in elderly hip-surgery patients. However, outcome from delirium is particularly poor when other risk factors are present.

The effect of the anticholinergic burden on duration and severity of delirium in older hip-surgery patients with and without haloperidol prophylaxis: A post hoc analysis.

BACKGROUND: Anticholinergic acting drugs have been associated with delirium in older patients. OBJECTIVE: To examine the association between the anticholinergic burden (ACB) and the duration and severity of delirium in older hip-surgery patients with or without haloperidol prophylaxis. METHODS: Older patients with a postoperative delirium following hip surgery from a randomized controlled trial investigating the effects of haloperidol prophylaxis on delirium incidence were included in this study. The ACB was quantified using two different tools, the Anticholinergic Drug Scale and an Expert Panel. Using linear regression, the association between the ACB and delirium was analyzed. RESULTS: Overall delirium duration and severity were not significantly associated with the ACB. Also, no statistically significant differences were found in delirium duration or severity between the placebo and haloperidol treatment groups for the ACB groups. The protective effect of haloperidol on delirium duration and severity however tended to be present in patients with no or a low ACB but not or to a lesser extent in patients with an intermediate to high ACB. CONCLUSIONS: The ACB was not significantly associated with delirium duration or severity. Haloperidol prophylaxis tended to shorten delirium duration and decrease delirium severity in patients with no or a low ACB. To further explore the influence of anticholinergic acting drugs on delirium duration and severity and the effect of concomitant haloperidol use, additional research with a higher haloperidol dose, a larger study population, and ACB quantification taking drug exposure into account is warranted.

Development and validation of the delirium risk assessment score (DRAS).

PURPOSE: Development and validation of a delirium risk assessment score. Predisposing risk factors for delirium were used, which are easily assessed at hospital admission without additional clinical or laboratory testing. METHODS: A systematic literature search identified ten risk factors: acute admission, alcohol use > 4 units/day, cognitive impairment, ADL impairment, age > 75 years, earlier delirium, hearing/vision problems, number of medication ≥ 5, number of morbidities > 2 and male. The DRAS was developed in a mixed patient population (N = 842) by the use of univariate and multivariate analyses and -2 log-likelihood calculation to weigh the risk factors. Based on the sensitivity and specificity, a cutoff score was calculated. The validation was performed in 3 cohorts (N = 408, N = 186, N = 365). In cohort 3, the DRAS was compared (AUC, sensitivity and specificity) to 3 instruments (Inouye, Kalisvaart, VMS rules). RESULTS: The delirium incidence was 31.8%, 20.3%, 15.6% and 15.1%. All risk factors were independently predictive for delirium, except male. The multivariate analyses excluded morbidities. The final DRAS consists of 8 items; acute admission, cognitive impairment, alcohol use (3 points), ADLimpairment/mobilityproblems (2 points), higher age, earlier delirium, hearing/vision problems, and medication (1 point). The total score is 15 points and at a cut-of score of 5 or higher the patient is at risk of developing a delirium. The cutoff was at 5 or more points, AUC: 0.76 (95% CI 0.72-0.79), sensitivity 0.77, specificity 0.60. Validation cohorts AUC was 0.75 (95% CI 0.96-0.81), 0.76 (95% CI 0.70-0.83) and 0.78 (95% CI 0.70-0.87), sensitivity 0.71, 0.67 and 0.89 and specificity 0.70, 0.72 and 0.60. The comparison revealed the highest AUC for the DRAS. CONCLUSION: Based on an admission interview, the delirium risk can be easily evaluated using the DRAS shortlist score of predisposing risk factors for delirium in older inpatients.

Clinicians' communication with patients receiving a MCI diagnosis: The ABIDE project.

BACKGROUND: We aimed to explore clinicians' communication, including the discussion of diagnosis, cause, prognosis and care planning, in routine post-diagnostic testing consultations with patients with Mild Cognitive Impairment (MCI). METHODS: Thematic content analysis was used to analyze audiotaped consultations in which 10 clinicians (eight neurologists and two geriatricians) from 7 memory clinics, disclosed diagnostic information to 13 MCI patients and their care partners. We assessed clinician-patient communication regarding diagnostic label, cause, prognosis and care planning to identify core findings. RESULTS: Core findings were: clinicians 1) differed in how they informed about the MCI label; 2) tentatively addressed cause of symptoms; 3) (implicitly) steered against further biomarker testing; 4) rarely informed about the patient's risk of developing dementia; 5) often informed about the expected course of symptoms emphasizing potential symptom stabilization and/or improvement, and; 6) did not engage in a conversation on long-term (care) planning. DISCUSSION: Clinicians' information provision about the underlying cause, prognosis and implications for long-term (care) planning in MCI could be more specific. Since most patients and care partners have a strong need to understand the patient's symptoms, and for information on the prognosis and implications for the future, clinicians' current approach may not match with those needs.

Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half years.

OBJECTIVE: To study the outcome of delirium in elderly hip surgery patients. DESIGN: Prospective matched controlled cohort study. Hip surgery patients (n = 112) aged 70 years and older, who participated in a controlled clinical trial of haloperidol prophylaxis for delirium, were followed for an average of 30 months after discharge. Patients with a diagnosis of dementia or mild cognitive impairment (MCI) were identified using psychiatric interviews. Proportions of patients with dementia/MCI were compared across patients who had postoperative delirium and selected control patients matched for preoperatively assessed risk factors who had not developed delirium during index hospitalization. Other outcomes were mortality rate and rate of institutionalization. RESULTS: During the follow-up period, 54.9% of delirium patients had died compared to 34.1% of the controls (relative risk = 1.6, 95% CI = 1.0-2.6). Dementia or MCI was diagnosed in 77.8% of the surviving patients with postoperative delirium and in 40.9% of control patients (relative risk = 1.9, 95% CI = 1.1-3.3). Half of the patients with delirium were institutionalized at follow-up compared to 28.6% of the controls (relative risk = 1.8, 95% CI = 0.9-3.4). CONCLUSION: The risk of dementia or MCI at follow-up is almost doubled in elderly hip surgery patients with postoperative delirium compared with at-risk patients without delirium. Delirium may indicate underlying dementia.

Prevention of delirium in the elderly.

The incidence of delirium in the elderly in general hospitals is up to 20 to 65%. Delirium is associated with high mortality, increased morbidity, increased need for nursing surveillance, longer hospital stays and a high rate of institutionalization following discharge. Delirium is not recognized by clinicians in one- to two-thirds of all cases and is commonly overlooked or misattributed to dementia, depression, or senescence; confusional states in the hospitalized elderly are considered the rule, rather than the exception and cognitive function is rarely assessed. For prevention of delirium it is necessary to look for patients "at-risk" for delirium and to use instruments for screenings and severity. Also should the medical and nursing staff be made aware of prodromal symptoms for delirium, indicating a delirium is developing. Prevention requires multidisciplinary action with pharmacological and non pharmacological interventions (multifactor intervention). A pro-active consultation team (doctors and nurses) resulting in good basic medical- and nursing care have the best results concerning the prevention of delirium, reducing delirium incidence with more than 25%.

Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of a medical risk factor model.

OBJECTIVES: To evaluate risk factors for postoperative delirium in a cohort of elderly hip-surgery patients and to validate a medical risk stratification model. DESIGN: Prospective cohort study. SETTING: Medical school-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Six hundred three hip-surgery patients aged 70 and older screened for risk factors for postoperative delirium. MEASUREMENTS: Predefined risk factors for delirium were assessed on admission. One point was assigned for each of four risk factors present, resulting in three groups: low, intermediate, and high risk. Baseline screening and assessment included the Mini-Mental State Examination, the standardized Snellen test for visual impairment, chart review to determine Acute Physiological and Chronic Health Evaluation II score, and blood urea nitrogen to creatinine ratio. The primary outcome was postoperative delirium, as defined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria. All patients were screened daily for delirium. RESULTS: Incidence of delirium was 3.8% in the low-risk group (P<.001), 11.1% in the intermediate-risk group (P=.27, relative risk (RR)=3.0), and 37.1% in the high-risk group (P<.001, RR=9.8). Cognitive impairment at admission had the highest predictive value for postoperative delirium (coefficient of determination=0.15). Contrary to previous findings, age was an independent predictive factor for delirium. Moreover, postoperative delirium was four times as frequent in acute patients as in elective hip-replacement patients. CONCLUSION: The medical risk factor model is valid for elderly hip-surgery patients. Cognitive impairment, age, and type of admission are important risk factors for delirium in this surgical population.

Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.

OBJECTIVES: To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Large medical school-affiliated general hospital in Alkmaar, The Netherlands. PARTICIPANTS: A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. INTERVENTION: Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. RESULTS: The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted. CONCLUSION: Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.

Anesthesia and postoperative delirium in older adults undergoing hip surgery.

OBJECTIVES: To examine the effects of general anesthesia on the risk of incident postoperative delirium in older adults undergoing hip surgery. DESIGN: Secondary analysis of haloperidol prophylaxis for delirium clinical trial data. Predefined risk factors for delirium were assessed prior to surgery. Primary outcome was postoperative delirium. Study outcome was compared across patient groups who received either general or regional anesthesia, and for individuals receiving various perioperative medications (benzodiazepines, anticholinergics, and opioids), using multivariable logistic regression after controlling for potential confounders. Subgroup analyses based on baseline cognitive impairment and delirium risk were also undertaken. SETTING: Large medical school-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Five hundred twenty-six adults aged 70 and older undergoing hip surgery. MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). RESULTS: Sixty participants (11.4%) had incident postoperative delirium. One hundred eighty-nine (35.9%) received general anesthesia, 18 (9.5%) of whom developed postoperative delirium, and 337 (64.1%) received regional anesthesia, 42 (12.5%) of whom developed postoperative delirium (adjusted odds ratio=0.81, 95% confidence interval=0.43-1.52, P=.51). Results were stratified for baseline cognitive impairment, age, acute admission, perioperative medication and other delirium risk factors. Delirium was not independently associated with specific drugs or the medication classes opioids, benzodiazepines, and anticholinergics. CONCLUSION: General anesthesia has no distinct effect on incident postoperative delirium in older adults undergoing hip surgery. This also holds for individuals suffering from cognitive impairment or who are otherwise at risk for postoperative delirium. Perioperative use of narcotics, benzodiazepines, and anticholinergic agents was not associated with incident delirium in this cohort of older adults undergoing hip surgery.

Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients.

OBJECTIVE: Pathophysiological mechanisms leading to delirium are not clear. Age is a known risk factor and hypothesised to be accompanied by a low-grade inflammatory state. Previous studies have shown an association between delirium and circulating proinflammatory markers in acutely ill and postoperative patients. In light of the ageing/inflammation theory, we investigated the association of these markers with delirium in not acutely ill, elderly patients. METHODS: In a prospective nested case-control study levels of C-reactive protein (CRP), interleukin 6 (Il-6), insulin growth factor 1 (IGF-1) were measured pre-operatively in elderly patients admitted for hip-surgery. These levels were compared between patients who later developed a post-operative delirium and patients who did not. Patients were matched for age and disease severity. RESULTS: Eighteen patients who developed delirium post-operatively were matched with 50 controls. Median APACHE-scores were below 16 in both groups. Pre-operative serum concentrations of CRP, Il-6 and IGF-1 did not differ between groups. IL-6 levels were associated with a measure of cognitive impairment. CONCLUSION: In the present study no relationship was found between levels of pre-operative circulating pro-inflammatory markers and post-operative delirium in elderly patients, who were free from acute or severe disease.

Early symptoms in the prodromal phase of delirium: a prospective cohort study in elderly patients undergoing hip surgery.

OBJECTIVES: The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery. METHODS: This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium. RESULTS: Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium. CONCLUSIONS: Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.