Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: A controlled, open 24-month study of 246 patients

Dipartimento di Fisiologia e Patologia, Università degli Studi di Trieste, Trieste, Italy.
American Journal of Alzheimer s Disease and Other Dementias (Impact Factor: 1.63). 11/2004; 19(6):333-9.
Source: PubMed


The goal of this study was to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effect on delirium in vascular dementia (VaD). The results from this follow-up study suggest that although delirium is frequent in elderly, cognitively impaired patients, it might not be a simple consequence of acute disease and hospitalization. Rather, delirium can be secondary to brain damage and to metabolic disturbances. According to the Lewy body dementia model, delirium could be induced by a lack of acetylcholine in the brain. Rivastigmine may help reduce the frequency of delirium episodes and help shorten their duration. Additional studies are required to better define the causes of delirium, which currently has no definitive treatment.

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    • "Seven studies did not describe the randomization process clearly [21] [27] [29] [33] [36] [38] [44] [45], and one study was a controlled clinical trial [21] that had a high risk of allocation concealment and random sequence generation bias. Three studies were open-label studies [23] [29] [36], four studies had a single-blind design in which only the outcome assessor was blinded [23] [27] [31] [36] and three studies [16] [21] [44] were not blinded. In these cases, there was a high risk of bias in the blinding of the participants and personnel and outcome assessment. "
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    ABSTRACT: Representation of hospitalized patients with pre-existing cognitive impairment in pharmaceutical delirium trials is important because these patients are at high risk for developing delirium. The aim of this systematic review is to investigate whether patients with cognitive impairment were included in studies on pharmacological prophylaxis or treatment of delirium and to explore the motivations for their exclusion (if they were excluded). This study was a systematic review. A MEDLINE search was performed for publications dated from 1 January 1985 to 15 November 2012. Randomized and non-randomized controlled trials that investigated medication to prevent or treat delirium were included. The number of patients with cognitive impairment was counted, and if they were excluded, motivations were noted. The search yielded 4293 hits, ultimately resulting in 31 studies that met the inclusion criteria. Of these, five studies explicitly mentioned the percentage of patients with cognitive impairment that were included. These patients comprised a total of 8% (n=279 patients) of the 3476 patients included in all 31 studies. Ten studies might have included cognitively impaired patients but did not mention the exact percentage, and sixteen studies excluded all patients with cognitive impairment. The motivations for exclusion varied, but most were related to the influence of dementia on delirium. The exclusion of patients with pre-existing cognitive impairment hampers the generalizability of the results of these trials and leaves clinicians with limited evidence about the pharmacological treatment of this group of vulnerable patients who have an increased risk of side effects.
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    • "Furthermore, rivastigmine was associated with a more severe type of delirium, that is, a longer stay in intensive care unit. [103] The reported differences between the outcomes in case reports and the open labelled trial [105] and those in the randomized control trials may be attribuTable to the severity of medical illness, heterogeneous clinical samples and extent of polypharmacy. Similarly, further work would be required to identify whether the effectiveness of cholinesterase inhibitors may be confined to a distinct subgroup of people with delirium, for example, elderly with cognitive impairment. "
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    ABSTRACT: Delirium is a neuropsychiatric syndrome characterized by altered consciousness and attention with cognitive, emotional and behavioural symptoms. It is particularly frequent in elderly people with medical or surgical conditions and is associated with adverse outcomes. Predisposing factors render the subject more vulnerable to a congregation of precipitating factors which potentially affect brain function and induce an imbalance in all the major neurotransmitter systems. Early diagnosis of delirium is crucial to improve the prognosis of patients requiring the identification of subtle and fluctuating signs. Increased awareness of clinical staff, particularly nurses, and routine screening of cognitive function with standardized instruments, can be decisive to increase detection rates of delirium. General measures to prevent delirium include the implementation of protocols to systematically identify and minimize all risk factors present in a particular clinical setting. As soon as delirium is recognized, prompt removal of precipitating factors is warranted together with environmental changes and early mobilization of patients. Low doses of haloperidol or olanzapine can be used for brief periods, for the behavioural control of delirium. All of these measures are a part of the multicomponent strategy for prevention and treatment of delirium, in which the nursing care plays a vital role.
    Full-text · Article · Jun 2011
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    • "Most of the reports have consisted of small series of case reports associated with the use of rivastagmine in the treatment of delirium in older persons (Dautzenberg et al 2004; Kalisvaart et al 2004; van den Bliek & Maas 2004). Moretti et al (2004) conducted an open (nonrandomized) study of 246 patients with vascular dementia who exhibited symptoms of delirium. Their data suggest a positive effect, but more stringent and better-designed randomized studies are needed. "
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    ABSTRACT: Delirium is a common event in the hospitalized surgical patiens. The pathophysiology of delirium is incompletely understood yet, but numerous risk factors for the development of delirium have been already identified. A literature review was performed using the National Library of Medicine PubMed data-base and Web of Science, including all resources within the period 1991–2011, additional references were found through bibliography reviews of relevant articles. The key word "delirium" with the following terms:"intensive care unit","antipsychotics", "benzodiaz-epine", "opioids", "elderly", "management". Constraints limiting time period of publications or their language were not applied. Reference lists of publications identified by these procedures were hand-searched for additional relevant references. Delirium in the ICU (intensive care unit) is not only a frightening experience for the patient and his or her family; it is also a challenge for the nurses and physicians taking care of the patient. Furthermore, it is also associated with worse outcome, prolonged hospitalisation, increased costs, long-term cognitive impairment and higher mortality rates. Predisposing factors, such as age, impairment, and nature and severity of comorbidity, increase the risk of experiencing delirium during hospitalization. The management of delirium involves the concurrent search for and treatment of the underlying aetiology while actively controlling the symptoms of delirium. Antipsychotics are demonstrating efficacy in controlling the symptoms of delirium with less extrapyramidal side effects. Proper diagnosis and treatment is important in the medical setting and significantly decreases the burden on the patient, caregivers, and medical system.
    Full-text · Article · Jan 2011 · Activitas Nervosa Superior Rediviva
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