Publications

OBJECTIVE: To examine the association between biochemical markers of brain injury (MBI) and the inflammatory response in relation to neurocognitive deficiency (NCD) after cardiopulmonary bypass (CPB).

SUMMARY BACKGROUND DATA: In cardiac surgery, NCD is a common but underdiagnosed complication with an unclear pathophysiology leading to significant morbidity. Despite extensive investigation, identification of a MBI for clinical use and clarifying the pathophysiology of NCD have not been achieved.

METHODS: Forty patients undergoing CABG and/or valve procedures using CPB were administered a validated neurocognitive battery preoperatively and postoperatively at day 4 and 3 months. S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs preoperatively and postoperatively at 6 hours and day 4. C-reactive protein (CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified from serum. Impact of cardiotomy suction and antifibrinolytics on markers of brain injury was assessed.

RESULTS: The incidence of early NCD was 40% (16 of 40). NSE and tau protein at the 6-hour time point were both significantly elevated in the presence of NCD (NCD group) compared with those without NCD (NORM group) (8.69 +/- 0.82 vs. 5.98 +/- 0.61; P = 0.018 and 68.8 vs. 29.2%; P = 0.015; respectively). S-100b increase was not different between the NCD and NORM groups. Cardiotomy suction significantly elevated S-100b levels, whereas NSE and tau were not significantly influenced. Aprotinin did not have an effect on NCD or levels of MBIs. Also, the NCD group had significantly elevated CRP and peroxide levels compared with the NORM group at postoperative day 4 while C3a was significantly elevated at 6 hours.

CONCLUSION: NSE and tau are better associated with NCD and less influenced by cardiotomy suction compared with S-100beta. Inflammatory and oxidative stress is associated with NCD post-CPB.

BACKGROUND: The objective of this study was to determine if level of educational attainment, a marker of cognitive reserve, was associated with the cumulative risk of delirium among hospitalized elders.

METHODS: We performed a secondary analysis of two hospital-based studies. The first (study 1) was an observational study involving 491 admissions. The second study (study 2) involved consecutive admissions assigned to the usual care condition in a controlled clinical trial, and included 461 persons. All participants were elderly (aged 70+) and free from delirium at admission. The outcome was the occurrence of delirium, as rated by the Confusion Assessment Method during hospitalization.

RESULTS: In study 1 and 2, 22% and 14% of persons developed delirium (cumulative incidence), respectively. In both studies, risk of delirium was higher among persons with fewer years of education. Controlling for the effect of age, sex, dementia, comorbidity, and severity of illness, each year of completed education was associated with a 0.91 lower odds of delirium (95% confidence interval: 0.87, 0.95): compared to persons with 12 years of education, persons with 7 years of education had 1.6-fold increased odds of delirium (95% confidence interval: 1.4, 2.0).

CONCLUSION: Hospitalized older persons with low educational attainment are at increased risk for delirium relative to persons with more education. This finding may have implications for the role of cognitive reserve in characterizing individual differences in risk for delirium.

This narrative review examines serum biomarkers for the diagnosis and monitoring of delirium. Serum biomarkers for delirium fall into three major groups: 1) those that are present or elevated prior to disease onset-risk markers, 2) those that rise with onset and fall with recovery-disease markers, and 3) those that rise in proportion to the consequences of disease-end products. As risk markers, we examine serum chemistries and genetic risk markers. As disease markers, we examine serum anticholinergic activity, amino acids, melatonin, cytokines, cortisol, and gene expression. As end products of delirium, we examine markers of neuronal injury. Finally, we discuss methodological and biostatistical considerations for future biomarker studies. Identifying accurate biomarkers for delirium may shed further light into its pathophysiology and on the interrelationship between delirium and dementia.

OBJECTIVES: To compare outcomes of patients admitted to postacute skilled nursing facilities with delirium, subsyndromal delirium, and no delirium.

DESIGN: Observational cohort study.

SETTING: Seven skilled nursing facilities that specialize in postacute care within a single metropolitan region.

PARTICIPANTS: Five hundred four subjects chosen from 1,248 consenting subjects aged 65 and older who underwent mental status testing within 5 days of admission to the participating facilities. Subjects who met full Confusion Assessment Method (CAM) criteria were classified as delirious, those with one or more CAM criteria were classified as having subsyndromal delirium, and those with no CAM features were classified as having no delirium. All subjects with delirium and with available medical records were included. A random subset of subjects with no delirium and subsyndromal delirium with available medical records was included.

MEASUREMENTS: The medical records of all subjects underwent a structured review by trained research nurses who were masked to the subjects' initial delirium status. Records were reviewed for the development of new complications within the postacute setting and to determine whether the subjects were discharged within 30 days and, if so, the discharge destination. The National Death Index was used to assess 6-month mortality.

RESULTS: Subjects with delirium were more likely to experience one or more complications than subjects with no delirium (73% vs 41%, P < .01). Within 30 days of postacute admission, subjects with delirium were more than twice as likely to be rehospitalized (30% vs 13%), and less than half as likely to be discharged to the community (30% vs 73%) than subjects without delirium (differences P < .01). Subjects with subsyndromal delirium had outcomes intermediate between those with and without delirium. Finally, subjects admitted to the postacute setting with delirium experienced a 6-month mortality rate of 25.0%, compared with 5.7% in subjects admitted without delirium. Subjects with subsyndromal delirium had a 6-month mortality rate of 18.3%.

CONCLUSION: Patients admitted to postacute skilled nursing facilities with delirium are more likely to experience complications, rehospitalization, and death than patients without delirium. These findings support the need for improved case finding and management of delirium in postacute care.

OBJECTIVES: To investigate whether atherosclerosis of the ascending aorta, internal carotid arteries, and coronary arteries is predictive of postoperative delirium in subjects undergoing coronary artery bypass graft (CABG) surgery.

DESIGN: Prospective cohort study.

SETTING: Boston Veterans Affairs Healthcare System.

PARTICIPANTS: Thirty-six male veterans undergoing primary CABG surgery.

MEASUREMENTS: Subjects underwent Duplex ultrasound to assess stenosis in the internal carotid arteries. Information on the ascending aortic plaque, as assessed by transesophageal echocardiogram, and the number of coronary vessels bypassed was collected. To create an atherosclerosis score, the number of atherosclerotic areas was added. A validated delirium battery was administered to the subjects preoperatively and on postoperative Days 2 and 5.

RESULTS: Fifteen subjects (41.7%) developed delirium postoperatively. In bivariate analysis, carotid stenosis of 50% or more (relative risk (RR)=3.5, 95% confidence interval (CI)=1.5-8.1) and moderate-severe ascending aortic plaque (RR=2.9, 95% CI=1.0-8.5) were significantly associated with the development of delirium. There was a trend toward a significant association for three or more vessels bypassed (RR=9.6, 95% CI=0.6-145.3). After controlling for age, baseline cognition, and medical comorbidity, the atherosclerosis score was significantly associated with postoperative delirium (adjusted RR=2.7, 95% CI=1.1-6.8).

CONCLUSION: In this preliminary report, atherosclerosis in the carotid arteries, aorta, and coronary circulation is associated with the development of delirium after CABG surgery. Further investigation into atherosclerosis as a risk factor for delirium is warranted.

Although delirium has been shown to be a common, morbid, and costly problem for hospitalized older people, evidence has mounted that it may persist for weeks or months. Therefore, concern about delirium can no longer be confined to acute care. After an acute hospitalization, many older people are discharged to postacute care (PAC) facilities–rehabilitation hospitals and skilled nursing facilities. Although several models designed to prevent delirium in the hospital setting have been described, there have been few such efforts in the PAC setting. This article describes the development of a multifactorial delirium abatement program (DAP), a new model of care for older patients admitted to the postacute skilled nursing facility with delirium. The DAP is a nurse-led, unit-based intervention. The program consists of four modules based on best practices as defined by the peer-reviewed literature: standardized screening for symptoms and signs of delirium upon admission to the PAC unit, assessment and treatment of possible causes of and contributors to delirium, prevention and management of common delirium complications, and restoration of patient cognitive and self-care function. This article also presents the process of facility introduction, staff education on DAP content, and multidisciplinary outreach. Key strategies for DAP implementation are reviewed. Program adoption challenges and corresponding model refinements to enhance adherence and overall care quality are highlighted. Last, clinical adaptation of this research-derived program is discussed.

OBJECTIVE: To determine whether preoperative characteristics influence quality of life outcomes 1, 6, and 12 months after joint replacement surgery.

METHODS: Patients (n = 222) with osteoarthritis undergoing primary joint replacement surgery at a university hospital between November 1990 and March 1993 were prospectively studied. Bodily pain and physical function were assessed preoperatively and at the 3 postoperative time points using the Medical Outcomes Study 36 Item Short Form Health Survey.

RESULTS: Bodily pain and physical function improved after joint replacement. At 1 month after surgery, despite improvements in bodily pain, physical function deteriorated. Preoperative bodily pain and physical function, demographic characteristics, and social support were significant correlates of improvement in bodily pain and physical function.

CONCLUSIONS: Patients experienced dramatic improvements in bodily pain and physical function after joint replacement. However, decline in physical function at 1 month implies significant need for prolonged informal or formal patient assistance with basic physical function after surgery. Greater preoperative social support was associated with improved bodily pain and physical function outcomes.

BACKGROUND: Delirium is costly, common, and may persist for weeks or months. Therefore, the adverse impact of delirium on loss of independence may occur in the post-acute setting rather than in the hospital. The purpose of this study is to describe the rate of delirium persistence and identify baseline patient characteristics that are associated with delirium persistence at 1 month among newly admitted post-acute facility patients who were admitted with delirium.

METHODS: Patients were recruited from 4 Boston area skilled nursing facilities specializing in post-acute care (PAC). Assessment instruments included the Confusion Assessment Method Diagnostic Algorithm, the modified Delirium Symptom Interview, the Memorial Delirium Assessment Scale (MDAS), and the Blessed Dementia Rating Scale (BDRS). Multiple logistic regression analyses were used to identify patient characteristics associated with delirium persistence (at 1 month).

RESULTS: Nearly 51% of the 85 delirious patients enrolled in this study had delirium at their 1-month follow-up assessment. Four patient factors associated with delirium persistence were identified: older age (> or =85 years), severe delirium at PAC admission (MDAS score >15), prehospital cognitive impairment based on proxy report [BDRS], and the presence of all 8 modified Delirium Symptom Interview symptoms at PAC admission. Our model has very good predictive power (area under the receiver operating characteristic = 0.85).

CONCLUSIONS: Delirium is persistent in the post-acute setting. If verified in further research, the risk factors found in this study could be used to identify patients who are likely to have delirium after 1 month, and may prove useful in developing and targeting interventions of care.

OBJECTIVES: To determine the prevalence of delirium symptoms at the time of admission to post-acute facilities, the persistence of delirium symptoms in this setting, and the association of delirium symptoms with functional recovery.

DESIGN: Prospective cohort study.

SETTING: Eighty-five post-acute care facilities: 55 rehabilitation hospitals and 30 skilled nursing facilities in 29 states.

PARTICIPANTS: Five hundred fifty-one consenting patients aged 65 and older newly admitted to participating facilities from acute care hospitals.

MEASUREMENTS: Data were collected as part of a field study effort related to the Minimum Data Set (MDS). Basic demographic data, medical comorbidity, delirium symptoms, and functional status–activities of daily living (ADLs) and instrumental activities of daily living (IADLs)–were obtained from MDS assessments performed within 4 days of admission and again 1 week later by the patient's primary nurse. Six delirium symptoms (easily distracted, periods of altered perception, disorganized speech, periods of restlessness, periods of lethargy, and mental function varies over the course of a day) were assessed after appropriate training.

RESULTS: Of the 551 patients (mean age +/- standard deviation 78 +/- 7, 64% women), 126 had delirium symptoms on post-acute admission, for an overall prevalence of 23%. In patients with delirium symptoms on the admission assessment, 1 week later, 14% had completely resolved, 22% had fewer delirium symptoms, 52% had the same number of symptoms, and 12% had more symptoms. Of those with no delirium symptoms on admission, 4% had new symptoms 1 week later. Patients who had the same number of or more delirium symptoms at the second assessment had significantly worse ADL and IADL recovery than those with fewer or resolved delirium symptoms or those with no delirium symptoms at either assessment. Persistent delirium symptoms remained significantly associated with worse ADL and IADL recovery after adjusting for age, comorbidity, dementia, and baseline functional status.

CONCLUSIONS: The data from this study provide strong preliminary evidence that, in patients newly admitted to post-acute care facilities from acute care hospitals, delirium symptoms are prevalent, persistent, and associated with poor functional recovery. Educational efforts are warranted to help post-acute facility staff recognize and manage this common and morbid condition.