Reducing delirium after hip fracture: a randomized trial.

OBJECTIVES: Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture. DESIGN: Prospective, randomized, blinded. SETTING: Inpatient academic tertiary medical center. PARTICIPANTS: 126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or "usual care." A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm. RESULTS: The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment. CONCLUSIONS: Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients.

Endogenous anticholinergic substances may exist during acute illness in elderly medical patients.

BACKGROUND: The purpose of this study was to determine if serum anticholinergic activity (SACA) arises from endogenous substances produced during illness. METHODS: Elderly medical inpatients (N = 612) were screened for anticholinergic medication use in the week prior to the study by interviews of subjects and proxies and review of emergency room, hospital, and nursing home medication administration records. Of 24 subjects without a recent anticholinergic medication history, 15 were recruited and 10 completed the study. Serum samples were obtained on Day 2 of hospital admission. SACA was measured using a radionuclide displacement assay. Medications taken by subjects were assayed for central muscarinic receptor binding at therapeutic concentrations. Results. Eight of the ten subjects had SACA detectable in the serum. No medication used by these subjects had anticholinergic activity at usual therapeutic concentrations. CONCLUSIONS: Endogenous anticholinergic substances may exist during acute illness. Characterization of such substances may increase the depth of our understanding of delirium and lead to useful intervention strategies.

Differing perceptions of end-of-life care in long-term care.

BACKGROUND: Care team members may have different views on end-of-life care, which may influence perceptions of that care. METHODS: Twenty-seven consecutive deaths at a long-term care facility were identified. A structured interview of primary care team members (physician, nurse, and aide) was administered. The interview asked comparable questions to each group on a Likert scale (1 = least satisfied; 4 = most satisfied) regarding the resident's experience in the last 3 days of life. Areas assessed were pain, comfort, emotional support, adequacy of information provided to families, whether direct care needs were met, supportive care, time spent with resident, number of symptoms present at the end of life, and quality of death. Repeated measures analysis of variance was used to determine if the mean values of various response measures differed significantly by rater group (i.e., physicians, nurses, or aides). RESULTS: Aides perceived more resident pain compared to physicians or nurses. Physicians' perceptions of emotional support provided to families were lower than those of aides or nurses. CONCLUSIONS: This study demonstrates differing perceptions by care team members regarding end-of-life care. Areas of difference include pain and emotional support provided to families. Because effective team functioning requires understanding and recognition of different perceptions of team members, clarifying and addressing the reasons for these differences may improve both job satisfaction on the part of care team members, as well as the quality of end-of-life care delivered.

Delirium is independently associated with poor functional recovery after hip fracture.

OBJECTIVE: To evaluate the role of delirium in the natural history of functional recovery after hip fracture surgery, independent of prefracture status. DESIGN: Prospective cohort study. SETTING: Orthopedic surgery service at a large academic tertiary hospital, with follow-up extending into rehabilitation hospitals, nursing homes, and the community. PARTICIPANTS: One hundred twenty-six consenting subjects older than 65 years (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment at enrollment to ascertain prefracture status through interviews with the patient and designated proxy and review of the medical record. Interviews included administration of standardized instruments (Activities of Daily Living (ADL) Scale, Blessed Dementia Rating Scale, Delirium Symptom Interview) and assessment of ambulation, and prefracture living situation. Medical comorbidity, the nature of the hip fracture, and the surgical repair were obtained from the medical record. All subjects underwent daily interviews for the duration of the hospitalization, including the Mini-Mental State Examination and Delirium Symptom Interview, and delirium was diagnosed using the Confusion Assessment Methods algorithm. Patients and proxies were recontacted 1 and 6 months after fracture, and underwent interviews similar to those at enrollment to determine death, persistent delirium, decline in ADL function, decline in ambulation, or new nursing home placement. RESULTS: Delirium occurred in 52/126 (41%) of patients, and persisted in 20/52 (39%) at hospital discharge, 15/52 (32%) at 1 month, and 3/52 (6%) at 6 months. Patients aged 80 years or older, and those with prefracture cognitive impairment, ADL functional impairment, and high medical comorbidity were more likely to develop delirium. However, after adjusting for these factors, delirium was still significantly associated with outcomes indicative of poor functional recovery 1 month after hip fracture: ADL decline (odds ratio (OR) = 2.6; 95% confidence interval (95% CI), 1.1- 6.1), decline in ambulation (OR = 2.6; 95% CI, 1.03-6.5), and death or new nursing home placement (OR = 3.0; 95% CI, 1.1-8.4). Patients whose delirium persisted at 1 month had worse outcomes than those whose delirium had resolved. CONCLUSIONS: Delirium is common, persistent, and independently associated with poor functional recovery 1 month after hip fracture even after adjusting for prefracture frailty. Further research is necessary to identify the mechanisms by which delirium contributes to poor functional recovery, and to determine whether interventions designed to prevent or reduce delirium can improve recovery after hip fracture.

Large neutral amino acid changes and delirium in febrile elderly medical patients.

A hypothesized but unexplored mechanism for delirium in older persons is that changes in plasma large neutral amino acid (LNAA) concentrations alter brain serotonin levels, result in neurotoxicity, or both. Therefore we performed a prospective study of 21 acutely febrile long-term-care residents to study the relationship between LNAA changes and delirium. Plasma LNAA concentrations were evaluated during illness and 1 month later. Delirium was diagnosed by using the Confusion Assessment Method. Other data included age, body mass index, cognitive impairment, comorbidity, gender, maximum temperature, and medication use. Seven subjects (33%) were delirious during febrile illness. Although the phenylalanine (PHE)/LNAA ratio was higher during illness in both delirious and nondelirious groups, a two-sample t test demonstrated that delirium was associated with a higher illness PHE/LNAA ratio (p = .03). The amount of change in PHE/LNAA from illness to recovery was not different between the delirious and nondelirious groups. Tryptophan/LNAA was not associated with delirium during illness or at recovery. These findings identify another potentially fruitful area of investigation for the prevention and treatment of delirium in older persons.

Resident characteristics associated with mortality in long-term care nursing homes: is there a gender difference?

OBJECTIVE: To examine the gender-specific association between characteristics in established long-term care residents and 1-year risk of mortality. DESIGN: A retrospective cohort study. SETTING: The Hebrew Rehabilitation Center for Aged, a 725-bed long-term care facility in Boston, Massachusetts. The 778 participants included 188 men (24%) and 590 women (76%). MEASUREMENTS: Minimum Data Set (MDS) information, including items from the following sections: cognition, communication, psychosocial, functional, diseases, health conditions and medication use. RESULTS: Survival curves were significantly different for men and women (log rank test, P = 0.004). Based on proportional hazards analyses, increased age, (RR(m)=1.07, RR(w)=1.05), functional impairment (RR(m)=1.07, RR(w)=1.04), and weight loss (RR(m)=2.03, RR(w)=2.24) were associated with increased mortality in men and women. Additionally, shortness of breath (RR = 2.87) and lower body mass index (RR = 2.25) were associated with higher mortality in men, and diabetes (RR = 2.42), pressure ulcers (RR = 1.99), anemia (RR = 1.98), congestive heart failure (RR = 1.87), and a recent fall (RR = 1.88) were associated with higher mortality in women. CONCLUSIONS: Characteristics associated with 1-year mortality differ between men and women. These readily available data could be useful in making medical decisions and advance directives planning. Furthermore, these data may be beneficial in developing quality improvement initiatives and mortality prediction modeling.

Neural mechanisms of delirium: current hypotheses and evolving concepts.

The purpose of this article is to review current knowledge regarding potential neural mechanisms of delirium. A MEDLINE search for relevant English language articles was undertaken using various combinations of delirium (including cognitive disorders, encephalopathy, and confusion) with pathogenesis and pathophysiology. These articles were scanned for content related to hypotheses concerning the neurobiology of delirium. Additional references were obtained from a manual search of the bibliography of these articles. A secondary MEDLINE search of delirium with the mechanism in question (i.e., serotonin, acetylcholine, etc.) was then undertaken. Literature review was last updated as of April 1998. Despite being a common problem among elderly patients, the mechanisms of delirium are poorly understood. Delirium is a syndrome that may occur as the result of multiple complex interacting neurotransmitter systems and pathologic processes. The neurotransmitters acetylcholine and serotonin may play particularly important roles in common medical and surgical delirium. Other neurotransmitters such as dopamine and gamma-aminobutyric acid each may be involved in the development of delirium under special conditions. Other neurobiologic factors such as cytokines, cortisol abnormalities, and oxygen free radicals will require further study to define their role in delirium. Distinct neuropathologic processes leading to delirium are beginning to be defined. Such mechanisms may differ in various clinical settings. There is probably no final common pathway to delirium, but rather, delirium is the final common symptom of multiple neurotransmitter abnormalities. Further situation-specific studies of delirium pathophysiology should lead to more effective prevention and treatment strategies.

Serum anticholinergic activity changes with acute illness in elderly medical patients.

BACKGROUND: Elevated serum anticholinergic activity levels have been associated with delirium in cross-sectional studies of ill older persons. This study used serial measures of serum anticholinergic activity levels to determine whether these levels change following illness resolution, and if such changes are specific to those with delirium. METHODS: Twenty-two nursing home residents with a febrile illness had serum specimens drawn and were evaluated for the presence of delirium during the acute illness and at 1-month follow-up. Delirium was diagnosed using the Confusion Assessment Method. Serum anticholinergic activity was determined using a previously described radionuclide competitive-binding assay. RESULTS: Delirium was present during illness in 8 of 22 subjects (36%), and had resolved by 1-month follow-up in all but one resident. Serum anticholinergic activity levels were significantly higher during illness than at 1-month follow-up in both the delirious (0.69 +/- 0.85 nM atropine equivalents/200 microL sample versus 0.10 +/- 0.16; p = .06) and non-delirious (0.65 +/- 0.51 nM atropine equivalents/200 microL sample versus 0.08 +/- 0.12; p < .001) groups. Medication changes did not seem to be related to changes in serum anticholinergic activity. CONCLUSIONS: In older nursing home residents with a fever, serum anticholinergic activity appears to be elevated during illness, and declines following recovery from illness. This effect does not seem to be specific to those residents with delirium, nor does it seem related to medication changes.

Delirium in the elderly. Optimal management.

Delirium is common, morbid and costly, especially among hospitalised elderly patients. Nonetheless, it remains under-recognised and often poorly managed. This article summarises the 5 key steps in the optimal management of delirium. The first step is to precisely define the syndrome of delirium, using key features described in the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) [DSM-IV] or the Confusion Assessment Method. Key features include an acute onset of mental status change, fluctuating course, the presence of inattention, and either disorganised thinking or an altered level of of consciousness. The second step involves the identification of patients at high risk of delirium before it develops, so that preventive measures can be implemented. Risk factors for delirium include advanced age, dementia, impaired functional status, chronic comorbidities and medications, and the severity of the acute illness or surgery. The third step is improved recognition of delirium. Very often, the presence of delirium is neither diagnosed nor properly documented in the medical record. The fourth step is to appropriately evaluate the delirious patient to assess all important contributors to the syndrome. This evaluation will usually involve a careful history, medication review, physical examination and selected laboratory testing. The fifth, and most important, step is the management of the delirious patient. The key elements of management are treating the primary condition(s) leading to delirium, removing all treatable contributing factors, maintaining behavioural control, and supporting the patient and their family.

A practical approach to identifying mortality-related factors in established long-term care residents.

OBJECTIVE: Determining prognosis is an important part of medical planning for long-term care residents. Clarifying the resident characteristics associated with increased mortality has received little attention from investigators, and many approaches that have been suggested are unsuitable for widespread use. Using a readily available database, we sought to determine factors associated with 1-year mortality in established long-term care residents. DESIGN: A retrospective cohort study. SETTING: A 725-bed long-term care facility. MEASUREMENTS: We examined Minimum Data Set (MDS) information on 780 residents from April 1994 through August 1997. The association between death and 65 resident factors, covering a broad array of physical, functional, medical, and psychosocial measures, was examined initially in bivariate proportional hazards models. Putative factors with P values < .10 in bivariate analysis were considered in the multivariate analysis. Using these factors, we employed a forward step-wise multivariate proportional hazards regression method to select the set of factors associated independently with mortality at a P value < .05. A mortality score was developed by assigning points to each factor based on the risk ratio in the multivariate proportional hazards model. The performance characteristics of the model were examined using logistic regression. RESULTS: Forty-four of the 65 factors examined were associated with 1-year mortality in bivariate proportional hazards analysis. Eight of these 44 factors were associated with 1-year mortality in the multivariate proportional hazards regression. These factors were functional impairment, weight loss, shortness of breath, male gender, low body mass index, swallowing problems, congestive heart failure, and advanced age. A higher mortality score was associated with a higher death rate in the subsequent year. The model demonstrated good performance with an area under the ROC curve of 0.77. CONCLUSIONS: Using a widely available database that requires no additional medical testing or staff training, a useful model for identifying factors associated with 1-year mortality in established long-term care residents can be developed. Widespread use of such a practical approach to assess mortality risk could be of benefit to patients, their families, and physicians for informing care plan decisions.

The association of serum anticholinergic activity with delirium in elderly medical patients.

To investigate the hypothesis that elevated serum anticholinergic activity is independently associated with delirium in ill elderly persons, the authors performed a cross-sectional study of 67 acutely ill older medical inpatients. The presence of delirium was evaluated with the Confusion Assessment Method, and the presence of many delirium symptoms was measured by the Delirium Symptom Interview. Demographic data and clinical characteristics that may be important for the development of delirium were also collected. Logistic regression techniques demonstrated that elevated serum anticholinergic activity was independently associated with delirium. Among the subjects with delirium, a greater number of delirium symptoms was associated with higher serum anticholinergic activity.

Peptidyl-glycine alpha-amidating monooxygenase is present in islet secretory granules of the anglerfish, Lophius americanus.

Anglerfish islet secretory granules have been examined for the presence of an enzyme which could perform C-terminal amidation of glucagon-like peptide II and possibly anglerfish peptide Y. Using [125I]D-Tyr-Val-Gly as substrate, a peptidyl-glycine alpha-amidating monooxygenase (PAM) was detected in islet secretory granule lysates. The enzyme is active between pH 6.0 and 8.5 and exhibits maximal activity near pH 7.0. The islet PAM requires Cu2+, ascorbate, and molecular oxygen for activity. Other divalent metal ions and redox cofactors were tested and found to be inactive in the assay. Even though added Cu2+ and ascorbate are required for detecting islet PAM activity, when these factors were incubated with substrate in the absence of secretory granule lysate, no activity was observed. It was also found that the addition of higher than optimal concentrations of either Cu2+ or ascorbate inhibited amidating activity. The results demonstrate that a PAM is present in secretory granules of anglerfish islet tissue. The characteristics of the islet PAM are similar to those of PAMs identified and characterized in other tissues which produce bioactive C-terminally amidated peptides.