To determine pre- and post-transplantation risk factors for delirium onset and severity during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT).
Patients and Methods
Ninety adult patients with malignancies admitted to the Fred Hutchinson Cancer Research Center for their first HSCT were assessed prospectively from 1 week before transplantation to 30 days after transplantation. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale. Potential risk factors were assessed by patient self-report, charts, and computerized records. Multivariable analysis of time to onset of a delirium episode was undertaken using Cox proportional hazards regression with time-varying covariates. Analysis for delirium severity was carried out using a linear mixed effects model. Validation and sensitivity analyses were performed on the final models.
Forty-five patients (50%) experienced a delirium episode. Pretransplantation risk factors for onset and higher severity of delirium were higher mean alkaline phosphatase and blood urea nitrogen (BUN) levels. Poorer pretransplantation executive functioning was also associated with higher delirium severity. Higher doses of opioid medications were the only post-transplantation risk factor for delirium onset (hazard ratio, 1.05; 95% CI, 1.02 to 1.08). Higher opioid doses, current and prior pain, and higher BUN levels were post-transplantation risk factors for greater delirium severity (all P < .01).
Pre- and post-transplantation factors can assist in identifying patients who are at risk for delirium during myeloablative HSCT and may enable clinical interventions to prevent delirium onset or decrease delirium symptoms.
Delirium is associated with a host of negative outcomes, including increased risk of mortality, longer hospital stay, and poor long-term cognitive function. The pathophysiology of delirium is not well understood. Cancer patients undergoing a bone marrow transplant (BMT) are at high risk for developing delirium and Proton Magnetic Resonance Spectroscopy (1H-MRS) could lead to better understanding of the delirium process.
Fourteen BMT patients and 10 controls completed 1H-MRS, positioned above the corpus callosum, shortly after delirium onset or at study end if no delirium occurred.
In the BMT-delirium group, statistically significantly elevated tCho/tCr was found in contrast to the BMT-no delirium group (p<0.05). The BMT–delirium group also showed statistically significantly lesser NAA/tCho compared to both controls (p=0.01) and the BMT–no delirium group (p=0.04).
Elevated choline and reduced NAA indicate inflammatory processes and white matter damage as well as neuronal metabolic impairment. Further research is needed to separate the choline peaks, as well as more detailed collection of medication regimens to determine whether a higher choline concentration is a function of the delirium process or cancer treatment effects.
delirium; spectroscopy; choline; cancer; magnetic resonance imaging; cognition
Postoperative delirium and its risk factors had been widely reported in several kinds of surgeries; however, there is only one known article relative to postoperative delirium in spinal surgery. We retrospectively examined the incidence of postoperative delirium and the probable risk factors in patients undergoing spinal surgery in our hospital, with the same aged non-delirium patients as controls, over a 6-month period. Studies about postoperative delirium were reviewed and referenced for variable factors collecting in our study. T tests, χ2 test and logistic regression analysis were performed to evaluate the various factors related to postoperative delirium. A total of 18 patients (3.3%), all of them were aged 54 years or older, had postoperative delirium after surgery. Patients without postoperative delirium aged 54 years or older served as the control group. The percentage of patients older than 65 years (P = 0.003), with comorbid diseases such as diabetes mellitus (P = 0.042) or central nervous system disorders (P = 0.013), with a surgical history (P = 0.028) in delirium group was larger than the control group. The absolute number of medications being taken before the operation in the delirium patients was also more than the control group (P = 0.000). The percentage of patients transfused with 800 mL or more blood was also larger (P = 0.024) in delirium group was larger than the control group. Logistic regression analysis showed that central nervous system disorder (OR 6.480), surgical history (OR 3.499), age older than 65 years (OR 3.390), diabetes mellitus (OR 2.981), transfused 800 mL or more blood (OR 2.537), and hemoglobin less than 100 g/L (OR 0.281) were significantly related to the occurrence postoperative delirium. Our findings suggest that postoperative delirium in spinal surgery can also occurred in younger patients and with an acceptable incidence in total. The risk for postoperative delirium is multifactorial. More prospective research is necessary in order to evaluate these and other risk factors in greater detail.
Postoperative delirium; Spinal surgery; Delirium observation screening (DOS) scale; Logistic regression analysis
High plasma cortisol levels can cause acute cognitive and neuropsychiatric dysfunction, and have been linked with delirium. CSF cortisol levels more closely reflect brain exposure to cortisol, but there are no studies of CSF cortisol levels in delirium. In this pilot study we acquired CSF specimens at the onset of spinal anaesthesia in patients undergoing hip fracture surgery, and compared CSF and plasma cortisol levels in delirium cases versus controls.
Delirium assessments were performed the evening before or on the morning of operation with a standard battery comprising cognitive tests, mental status assessments and the Confusion Assessment Method. CSF and plasma samples were obtained at the onset of the operation and cortisol levels measured. Twenty patients (15 female, 5 male) aged 62 - 93 years were studied. Seven patients were diagnosed with delirium. The mean ages of cases (81.4 (SD 7.2)) and controls (80.5 (SD 8.7)) were not significantly different (p = 0.88). The median (interquartile range) CSF cortisol levels were significantly higher in cases (63.9 (40.4-102.1) nmol/L) than controls (31.4 (21.7-43.3) nmol/L; Mann-Whitney U, p = 0.029). The median (interquartile range) of plasma cortisol was also significantly higher in cases (968.8 (886.2-1394.4) nmol/L, than controls (809.4 (544.0-986.4) nmol/L; Mann Whitney U, p = 0.036).
These findings support an association between higher CSF cortisol levels and delirium. This extends previous findings linking higher plasma cortisol and delirium, and suggests that more definitive studies of the relationship between cortisol levels and delirium are now required.
S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium.
The study population were patients aged 65 years or more acutely admitted after hip fracture. Delirium was diagnosed by the Confusion Assessment Method and the subtype by Delirium Symptom interview. In maximal four serum samples per patient S100B and NSE levels were determined by electrochemiluminescence immunoassay.
Of 120 included patients with mean age 83.9 years, 62 experienced delirium. Delirious patients had more frequently pre-existing cognitive impairment (67% vs. 18%, p < 0.001). Comparing the first samples during delirium to samples of non-delirious patients, a difference was observed in S100B (median 0.16 versus 0.10 μg/L, p = < 0.001), but not in NSE (median 11.7 versus 11.7 ng/L, p = 0.97). Delirious state (before, during, after) (p < 0.001), day of blood withdrawal (p < 0.001), pre- or postoperative status (p = 0.001) and type of fracture (p = 0.036) were all associated with S100B level. The highest S100B levels were found 'during' delirium. S100B levels 'before' and 'after' delirium were still higher than those from 'non-delirious' patients. No significant difference in S100B (p = 0.43) or NSE levels (p = 0.41) was seen between the hyperactive, hypoactive and mixed subtype of delirium.
Delirium was associated with increased level of S100B which could indicate cerebral damage either due to delirium or leading to delirium. The possible association between higher levels of S100B during delirium and the higher risk of developing dementia after delirium is an interesting field for future research. More studies are needed to elucidate the role of S100B proteins in the pathophysiological pathway leading to delirium and to investigate its possibility as biomarker for delirium.
To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD).
A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer’s Disease Research Center’s patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis.
A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not.
Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD.
= Alzheimer disease;
= Clinical Dementia Rating;
= Information-Memory-Concentration subtest of the Blessed Dementia Rating Scale;
= Massachusetts Alzheimer’s Disease Research Center;
= Massachusetts General Hospital.
To determine the extent to which preoperative performance on tests of executive function and memory was associated with delirium after coronary artery bypass graft (CABG) surgery.
Prospective observational cohort study.
Two academic medical centers and one Department of Veterans Affairs medical center in Massachusetts.
Eighty subjects without preoperative delirium undergoing CABG or CABG-valve surgery completed baseline neuropsychological assessments with validated measures of memory and executive function.
Beginning on postoperative Day 2, a battery to diagnose delirium was administered daily. Confirmatory factor analysis (CFA) was used to define two cognitive domain composites (memory and executive function). The loading pattern of neuropsychological measures onto the latent cognitive domains was determined a priori. Poisson regression was used to model the association between neuropsychological performance and cognitive domain composite scores and risk of postoperative delirium. The association was expressed as the difference between impaired (0.5 standard deviations (SDs) below mean) and nonimpaired (0.5 SDs above mean) performers.
Forty subjects (50%) developed delirium. Measures of memory function were not significantly related to delirium. Of the executive function measures, verbal fluency, category fluency, Hopkins Verbal Learning Test learning, and backward recounting of days and months were significantly related to delirium. Preoperative mental status was a strong predictor of postoperative delirium. After controlling for age, sex, education, medical comorbidity, mental status, and the other cognitive domain, CFA cognitive domain composites suggest that risk for delirium is specific for executive functioning impairment (relative risk (RR) = 2.77, 95% confidence interval (CI) = 1.12–6.87) but not for memory impairment (RR = 0.49, 95% CI = 0.19–1.25).
Worse preoperative performance in executive function was independently associated with greater risk of developing delirium after CABG.
aged; delirium; CABG surgery; executive function; cognitive impairment; factor analysis
Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.
This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.
No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).
Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.
Nederlands Trial Register NTR1395
Delirium in older hospital inpatients appears to be associated with various adverse outcomes. The limitations of previous research on this association have included small sample sizes, short follow-up periods and lack of consideration of important confounders or modifiers, such as severity of illness, comorbidity and dementia. The objective of this study was to determine the prognostic significance of delirium, with or without dementia, for cognitive and functional status during the 12 months after hospital admission, independent of premorbid function, comorbidity, severity of illness and other potentially confounding variables.
Patients 65 years of age and older who were admitted from the emergency department to the medical services were screened for delirium during their first week in hospital. Two cohorts were enrolled: patients with prevalent or incident delirium and patients without delirium, but similar in age and cognitive impairment. The patients were followed up at 2, 6 and 12 months after hospital admission. Analyses were conducted for 4 patient groups: 56 with delirium, 53 with dementia, 164 with both conditions and 42 with neither. Baseline measures included delirium (Confusion Assessment Method), dementia (Informant Questionnaire on Cognitive Decline in the Elderly), physical function (Barthel Index [BI] and premorbid instrumental activities of daily living, IADL), the Mini-Mental State Examination (MMSE), comorbidity, and physiologic and clinical severity of illness. Outcome variables measured at follow-up were the MMSE, Barthel Index, IADL and admission to a long-term care facility.
After adjustment for covariates, the mean differences in MMSE scores at follow-up between patients with and without delirium were –4.99 (95% confidence interval [CI] –7.17 to –2.81) for patients with dementia and –3.36 (95% CI –6.15 to –0.58) for those without dementia. At 12 months, the adjusted mean differences in the BI were –16.45 (95% CI –27.42 to –5.50) and –13.89 (95% CI –28.39 to 0.61) for patients with and without dementia respectively. Patients with both delirium and dementia were more likely to be admitted to long-term care than those with neither condition (adjusted odds ratio 3.18, 95% CI 1.19 to 8.49). Dementia but not delirium predicted worse IADL scores at follow-up. Unadjusted analyses yielded similar results.
For older patients with and without dementia, delirium is an independent predictor of sustained poor cognitive and functional status during the year after a medical admission to hospital.
Postoperative delirium is associated with increased morbidity and mortality. Pre-existing cognitive impairment and depression have been frequently cited as important risk factors for this complication. This prospective cohort study was designed to determine if individuals who perform poorly on preoperative cognitive tests and/or exhibited depressive symptoms would be at high risk for the development of postoperative delirium.
One hundred nondemented patients, 50 years and older, scheduled for major, elective noncardiac surgery completed a preoperative test battery that included measures of global cognition, executive function and symptoms of depression. Known preoperative risk factors for delirium were collected and examined with the results of the preoperative test battery to determine the independent predictors of delirium.
The overall incidence of delirium was 16% and was associated with increased hospital length of stay (p<0.05) and an increased incidence of postoperative complications (p<0.01). Delirious subjects did not differ from their non-delirious cohorts with regard to their preoperative global cognitive function, preexisting medical comorbidities, age, anesthetic management or history of alcohol use. Preoperative executive scores (p<0.001) and depression (p<0.001), as measured by the Trail Making B test and Geriatric Depression Scale Short Form, respectively, were found to be independent predictors of postoperative delirium.
Low preoperative executive scores and depressive symptoms independently predict postoperative delirium in older individuals. A rapid, simple test combination including tests of executive function and depression could improve physicians’ ability to recognize patients who might benefit from a perioperative intervention strategy to prevent postoperative delirium.
Predictive models, such as acute physiology and chronic health evaluation II (APACHE-II), are widely used in intensive care units (ICUs) to estimate mortality. Although the presence of delirium is associated with a higher mortality in ICU patients, delirium is not part of the APACHE-II model. The aim of the current study was to evaluate whether delirium, present within 24 hours after ICU admission, improves the predictive value of the APACHE-II score.
In a prospective cohort study 2116 adult patients admitted between February 2008 and February 2009 were screened for delirium with the confusion assessment method-ICU (CAM-ICU). Exclusion criteria were sustained coma and unable to understand Dutch. Logistic regression analysis was used to estimate the predicted probabilities in the model with and without delirium. Calibration plots and the Hosmer-Lemeshow test (HL-test) were used to assess calibration. The discriminatory power of the models was analyzed by the area under the receiver operating characteristics curve (AUC) and AUCs were compared using the Z-test.
1740 patients met the inclusion criteria, of which 332 (19%) were delirious at the time of ICU admission or within 24 hours after admission. Delirium was associated with in-hospital mortality in unadjusted models, odds ratio (OR): 3.22 (95% confidence interval [CI]: 2.23 - 4.66). The OR between the APACHE-II and in-hospital mortality was 1.15 (95% CI 1.12 - 1.19) per point. The predictive accuracy of the APACHE-II did not improve after adding delirium, both in the total group as well as in the subgroup without cardiac surgery patients. The AUC of the APACHE model without delirium was 0.77 (0.73 - 0.81) and 0.78 (0.74 - 0.82) when delirium was added to the model. The z-value was 0.92 indicating no improvement in discriminative power, and the HL-test and calibration plots indicated no improvement in calibration.
Although delirium is a significant predictor of mortality in ICU patients, adding delirium as an additional variable to the APACHE-II model does not result in an improvement in its predictive estimates.
Delirium features can vary greatly depending on the postoperative population studied; however, most studies focus only on high-risk patients. Describing the impact of delirium and risk factors in mixed populations can help in the development of preventive actions.
The occurrence of delirium was evaluated prospectively in 465 consecutive nonventilated postoperative patients admitted to a surgical intensive care unit (SICU) using the confusion assessment method (CAM). Patients with and without delirium were compared. A multiple logistic regression was performed to identify the main risk factors for delirium in the first 24 h of admission to the SICU and the main predictors of outcomes.
Delirium was diagnosed in 43 (9.2%) individuals and was more frequent on the second and third days of admission. The presence of delirium resulted in longer lengths of SICU and hospital stays [6 days (3–13) vs. 2 days (1–3), p < 0.001 and 26 days (12–39) vs. 6 days (3–13), p <0.001, respectively], as well as higher hospital and SICU mortality rates [16.3% vs. 4.0%, p = 0.004 and 6.5% vs. 1.7%, p = 0.042, respectively]. The risk factors for delirium were age (odds ratio (OR), 1.04 [1.02-1.07]), Acute Physiologic Score (APS; OR, 1.11 [1.04-1.2]), emergency surgery (OR, 8.05 [3.58-18.06]), the use of benzodiazepines (OR, 2.28 [1.04-5.00]), and trauma (OR, 6.16 [4.1-6.5]).
Delirium negatively impacts postoperative nonventilated patients. Risk factors can be used to detect high-risk patients in a mixed population of SICU patients.
Delirium; Postoperative; Surgery; Confusion assessment method
Delirium is a state of confusion characterized by an acute and fluctuating decline in cognitive functioning. Delirium is common and deadly in older adults with dementia, and is often referred to as delirium superimposed on dementia, or DSD. Interventions that treat DSD are not well-developed because the mechanisms involved in its etiology are not completely understood. We have developed a theory-based intervention for DSD that is derived from the literature on cognitive reserve and based on our prior interdisciplinary work on delirium, recreational activities, and cognitive stimulation in people with dementia. Our preliminary work indicate that use of simple, cognitively stimulating activities may help resolve delirium by helping to focus inattention, the primary neuropsychological deficit in delirium. Our primary aim in this trial is to test the efficacy of Recreational Stimulation for Elders as a Vehicle to resolve DSD (RESERVE- DSD).
This randomized repeated measures clinical trial will involve participants being recruited and enrolled at the time of admission to post acute care. We will randomize 256 subjects to intervention (RESERVE-DSD) or control (usual care). Intervention subjects will receive 30-minute sessions of tailored cognitively stimulating recreational activities for up to 30 days. We hypothesize that subjects who receive RESERVE-DSD will have: decreased severity and duration of delirium; greater gains in attention, orientation, memory, abstract thinking, and executive functioning; and greater gains in physical function compared to subjects with DSD who receive usual care. We will also evaluate potential moderators of intervention efficacy (lifetime of complex mental activities and APOE status). Our secondary aim is to describe the costs associated with RESERVE-DSD.
Our theory-based intervention, which uses simple, inexpensive recreational activities for delivering cognitive stimulation, is innovative because, to our knowledge it has not been tested as a treatment for DSD. This novel intervention for DSD builds on our prior delirium, recreational activity and cognitive stimulation research, and draws support from cognitive reserve theory.
ClinicalTrials.gov identifier: NCT01267682
The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.
We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition.
Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100β (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).
In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted.
To date, delirium prevalence and incidence in acute hospitals has been estimated from pooled findings of studies performed in distinct patient populations.
To determine delirium prevalence across an acute care facility.
A point prevalence study.
A large tertiary care, teaching hospital.
311 general hospital adult inpatients were assessed over a single day. Of those, 280 had full data collected within the study's time frame (90%).
Initial screening for inattention was performed using the spatial span forwards and months backwards tests by junior medical staff, followed by two independent formal delirium assessments: first the Confusion Assessment Method (CAM) by trained geriatric medicine consultants and registrars, and, subsequently, the Delirium Rating Scale-Revised-98 (DRS-R98) by experienced psychiatrists. The diagnosis of delirium was ultimately made using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria.
Using DSM-IV criteria, 55 of 280 patients (19.6%) had delirium versus 17.6% using the CAM. Using the DRS-R98 total score for independent diagnosis, 20.7% had full delirium, and 8.6% had subsyndromal delirium. Prevalence was higher in older patients (4.7% if <50 years and 34.8% if >80 years) and particularly in those with prior dementia (OR=15.33, p<0.001), even when adjusted for potential confounders. Although 50.9% of delirious patients had pre-existing dementia, it was poorly documented in the medical notes. Delirium symptoms detected by medical notes, nurse interview and patient reports did not overlap much, with inattention noted by professional staff, and acute change and sleep-wake disturbance noted by patients.
Our point prevalence study confirms that delirium occurs in about 1/5 of general hospital inpatients and particularly in those with prior cognitive impairment. Recognition strategies may need to be tailored to the symptoms most noticed by the detector (patient, nurse or primary physician) if formal assessments are not available.
Geriatric Medicine; Mental Health; Epidemiology; Internal Medicine; Medical Education & Training
To determine the impact of delirium on post-discharge mortality in hospitalized older patients.
Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality.
This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clínicas of São Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival.
The sample included 199 patients, 66 (33%) of whom developed delirium (Group A). After one year, 33 (50%) group A patients had died, and 45 (33.8%) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post-discharge mortality were age ≥ 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007).
Delirium is associated with higher post-discharge mortality as a dependent predictor.
Delirium; Post-discharge mortality; Elderly; Post discharge; Survival
Delirium is an acute change in cognition which occurs frequently after coronary artery bypass graft (CABG) surgery. Cerebral microemboli, from plaque, air, or thrombus, have been hypothesized to contribute to delirium and cognitive decline after CABG. The purpose of this study was to determine if there was an association between cerebral microemboli and delirium after cardiac surgery. Non-delirious patients (n=68) were prospectively enrolled and underwent intraoperative monitoring of the middle cerebral arteries with transcranial Doppler (TCD). TCD signals were saved and analyzed postoperatively for microemboli manually, according to established criteria. Postoperatively, patients were assessed for delirium with a standardized battery. Thirty-three patients (48.5%) developed delirium after surgery. Microemboli counts (mean ± SD) were not significantly different in those with and without delirium (303 ±449 vs. 299 ±350; p=0.97). While intraoperative microemboli were not associated with delirium after CABG, further investigation into the source and composition of microemboli can further elucidate the long-term clinical impact of microemboli.
Delirium in patients with hip fractures lead to higher morbidity and mortality. Prevention in high-risk patients by prescribing low dose haloperidol is currently under investigation.
This prospective cohort surveillance assessed hip fracture patients for risk of developing a delirium with the Risk Model for Delirium (RD) score. High-risk patients (score ≥ 5 points) were treated with a prophylactic low-dose of haloperidol according to hospital protocol. Primary outcome was delirium incidence. Secondary outcomes were differences between high- and low-risk patients in delirium, length of stay (LOS), return to pre-fracture living situation and mortality. Logistic regression analysis was performed with age, ASA-classification, known dementia, having a partner, type of fracture, institutional residence and psychotropic drug use as possible confounders.
445 hip fracture patients aged 65 years and older were admitted from January 2008 to December 2009. The RD-score was completed in 378 patients, 173 (45.8%) high-risk patients were treated with prophylactic medication. Sensitivity was 71.6%, specificity 63.8% and the negative predictive value (NPV) of a score < 5 was 85.9%.
Delirium incidence (27.0%) was not significantly different compared to 2007 (27.8%) 2006 (23.9%) and 2005 (29.0%) prior to implementation of the RD- protocol.
Logistic regression analysis showed that high-risk patients did have a significant higher delirium incidence (42.2% vs. 14.1%, OR 4.1, CI 2.43-7.02). They were more likely to be residing at an alternative living situation after 3 months (62.3% vs. 17.0%, OR 6.57, CI 3.23-13.37) and less likely to be discharged from hospital before 10 days (34.9% vs. 55.9%, OR 1.63, CI 1.03-2.59). Significant independent risk factors for a delirium were a RD-score ≥ 5 (OR 4.13, CI 2.43-7.02), male gender (OR 1.93, CI 0.99-1.07) and age (OR 1.03, CI 0.99-1.07).
Introducing the delirium prevention protocol did not reduce delirium incidence.
The RD-score did identify patients with a high risk to develop a delirium. This high-risk group had a longer LOS and returned to pre-fracture living situation less often.
The NPV of a score < 5 was high, as it should be for a screening instrument. Concluding, the RD-score is a useful tool to identify patients with poorer outcome.
In critically ill patients, delirium is a serious and frequent disorder that is associated with a prolonged intensive care and hospital stay and an increased morbidity and mortality. Without the use of a delirium screening instrument, delirium is often missed by ICU nurses and physicians. The effects of implementation of a screening method on haloperidol use is not known. The purpose of this study was to evaluate the implementation of the confusion assessment method-ICU (CAM-ICU) and the effect of its use on frequency and duration of haloperidol use.
We used a tailored implementation strategy focused on potential barriers. We measured CAM-ICU compliance, interrater reliability, and delirium knowledge, and compared the haloperidol use, as a proxy for delirium incidence, before and after the implementation of the CAM-ICU.
Compliance and delirium knowledge increased from 77% to 92% and from 6.2 to 7.4, respectively (both, P < 0.0001). The interrater reliability increased from 0.78 to 0.89. More patients were treated with haloperidol (9.9% to 14.8%, P < 0.001), however with a lower dose (18 to 6 mg, P = 0.01) and for a shorter time period (5 [IQR:2–9] to 3 [IQR:1–5] days, P = 0.02).
With a tailored implementation strategy, a delirium assessment tool was successfully introduced in the ICU with the main goals achieved within four months. Early detection of delirium in critically ill patients increases the number of patients that receive treatment with haloperidol, however with a lower dose and for a shorter time period.
The pathophysiology of postoperative delirium remains poorly understood. The purpose of this study was to examine the relationship between serum cortisol level and occurrence of early postoperative delirium in patients undergoing coronary artery bypass graft (CABG) surgery.
A total of 243 patients undergoing elective CABG surgery were enrolled. Patients were examined twice daily during the first five postoperative days and postoperative delirium was diagnosed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Blood samples were obtained between 7 a.m. and 8 a.m. on the first postoperative day and serum cortisol concentrations were then measured. Multivariate logistic regression analyses were performed to identify risk factors of postoperative delirium.
Postoperative delirium occurred in 50.6% (123 of 243) of patients. High serum cortisol level was significantly associated with increased risk of postoperative delirium (OR 3.091, 95% CI 1.763-5.418, P < 0.001). Other independent risk factors of postoperative delirium included increasing age (OR 1.111, 95% CI 1.065-1.159, P < 0.001), history of diabetes mellitus (OR 1.905, 95% CI 1.001-3.622, P = 0.049), prolonged duration of surgery (OR 1.360, 95% CI 1.010-1.831, P = 0.043), and occurrence of complications within the first day after surgery (OR 2.485, 95% CI 1.184-5.214, P = 0.016). Patients who developed postoperative delirium had a higher incidence of postoperative complications and a prolonged duration of postoperative ICU and hospital stay.
Delirium was a common complication after CABG surgery. High serum cortisol level was associated with increased risk of postoperative delirium. Patients who developed delirium had outcomes worse than those who did not.
This study is intended to identify predictive factors of delirium, including risk factors and prodromal symptoms.
This study included sixty-five patients aged 65 years or older who had undergone hip surgery. Baseline assessments included age; gender; admission type (acute/elective); reason for surgery (fracture/replacement); C-reactive protein (CRP); Acute Physiology, Age, Chronic Health Evaluation (APACHE III); and the Mini-Mental State Examination (MMSE). The Korean version of the Delirium Rating Scale-Revised-98 (K-DRS-98) was used to assess prodromal symptoms daily before the onset of delirium.
Almost 28% (n=18) of the 65 patients developed delirium after surgery. Delirium in elderly patients after hip surgery was observed more often in older patients and those with acute admission, hip fracture, higher APACHE III score, lower MMSE score, and higher CRP levels within early days after the operation. Sleep-wake cycle disturbances, thought process abnormalities, orientation, and long-term memory in symptom items of K-DRS-98 were showed significant difference on 4 days before delirium, lability of affect on 3 days before, perceptual disturbances and hallucination, and visuo-spatial ability on 2 days before, and delusion, motor agitation, and short-term memory on the day before the occurrence of delirium. CRP levels within 24 hours and 72 hours after hospitalization were significantly higher in the delirium group.
Medical professionals must pay attention to behavioral, cognitive changes and risk factors in elderly patients undergoing hip surgery and to the prodromal phase of delirium. K-DRS-98 may help in identifying the prodromal symptoms of delirium in elderly patients after hip surgery.
Delirium; Elderly; Hip surgery; Prodromal; K-DRS-98
To establish feasibility for the hypothesis that patients in acute rehabilitation who are hospitalized for disorders not known to involve cerebral injury can have significant cognitive impairment.
A comparison of performances on neuropsychological tests between 2 samples of subjects: inpatients in an acute rehabilitation hospital without known cerebral disease and normal community-dwelling persons.
Acute inpatient rehabilitation hospital.
Patients and Participants
Nineteen hospitalized patients without delirium who were screened for pre-existing cerebral and psychiatric illness, dementia, and dependency in basic self-care skills before hospitalization. Eighteen community-dwelling persons who were not different in terms of age and education served as the control group.
Participants completed 10 commonly used neuropsychological tests of executive, language, and memory functions. Data were analyzed by using multivariate analysis of variance.
Main Outcome Measurements
Raw scores on the 10 neuropsychological tests.
Hospitalized patients performed significantly worse on 9 of 10 tests than community-dwelling participants. Older hospitalized participants had significantly greater cognitive impairment than younger hospitalized participants, which suggested increased susceptibility to effects of hospitalization on cognition.
Patients hospitalized without brain injury, and especially elderly patients, should be carefully monitored for cognitive deficits that may affect posthospitalization quality of living. Further research is needed to determine whether the cognitive deficits in such patients persist after discharge and affect functional independence, and to identify mechanisms for the deficits. Furthermore, the use of hospitalized participants without brain injury as control subjects in neuropsychological studies of brain injury should be balanced with an additional comparison group of matched, neurologically healthy, normal subjects who live in the community to control for cognitive impairments that are associated with acute hospitalization.
To investigate the use of drugs with anticholinergic properties (DAPs) and their associations with delirium and mortality among elderly patients with comorbidities.
425 patients (≥70 years of age) in geriatric wards and nursing homes were assessed. The use of DAPs was retrieved from their medical records. Delirium was diagnosed according to the DSM-IV criteria.
Of the 341 patients (80.2%) treated with multiple DAPs (≥2), 92 patients (27.0%) suffered from delirium, whereas 14 of 84 patients (16.7%) without DAP treatment had delirium (p = 0.050). In a logistic regression analysis with age, gender, and Charlson Comorbidity Index as covariates, DAP treatment did not predict delirium (odds ratio 1.67, 95% confidence interval 0.87–3.21). The 2-year mortality was 49.3% (n = 168) in DAP users and 35.7% (n = 30) in non-users, respectively (p = 0.026). In the Cox proportional hazard model adjusted for age, gender, and comorbidity, DAPs did not predict mortality (hazard ratio 1.12, 95% confidence interval 0.75–1.68).
The use of DAPs is very frequent among frail inpatients with comorbidities, but their use has no independent prognostic significance.
Anticholinergic effects; Comorbidities; Delirium; Dementia; Elderly patients
A retrospective review was conducted of 122 charts of patients with clinically diagnosed Alzheimer's disease (CDAD) who had participated in a longitudinal dementia study at the Mayo Clinic from 1965 to 1970. DSM-III-R diagnoses were assigned based on the longitudinal description of symptoms detailed in the Mayo Clinic medical records of the hospitalizations; clinic, home, and nursing home visits; and state hospital admissions. Thirty patients (25%) were found to have a delirium episode during their course of CDAD that occurred during inpatient admissions; 50% (15 of 30) of the delirium episode occurred in patients ages 80 to 89. Among patients with a delirium episode, 50% died within one year of the delirium episode and 64% died within two years. Of 13 patients, 10 (77%) had multiple delirium episodes within two years. Admitting diagnoses were mainly primary degenerative dementia of the Alzheimer's type (PDDAT) or PDDAT with delirium. Only 3 (10%) demented patients experienced delirium episodes during a medical admission. No deaths occurred during hospitalization for the years covered by this study. A psychiatric consultation was requested in only 17 (14%) patients; 88% of these patients received diagnoses involving PDDAT, late onset. An additional diagnosis included depressive disorders. Psychopharmacology was the major management strategy (82% of patients with a delirium episode received medication) with a resolution of symptoms within 48 hours. At discharge, only 2 (7%) patients failed to clear the increased degree of confusion.
To investigate the controlling efficacy of ondasetron and haloperidol in regard to the postcardiotomy delirium.
We included in this prospective, randomized, double-blinded study 80 patients who developed delirium after heart surgery with the application of heart lung-machine. The patients were divided into two, equally-sized groups, which on detection of delirium received ondasetron 8 mg iv or haloperidol 5 mg iv respectively. The statistical analysis compared the baseline and demographic characteristics of the two groups (age, gender, comorbidities, years of education, type of surgery etc.).
Both ondasetron and haloperidol had very good delirium controlling effects, without statistically significant differences.
Ondasetron and haloperidol are efficient agents as far as the treatment of postcardiotomy delirium is concerned. As, in addition, ondasetron bares milder side-effects, we believe this could be the agent of choice in patients developing postcardiotomy delirium in the future.