Delirium and long-term cognitive impairment

ArticleinInternational Review of Psychiatry 21(1):30-42 · February 2009with15 Reads
DOI: 10.1080/09540260802675031 · Source: PubMed
Abstract
Delirium is a severe, acute neuropsychiatric syndrome that is highly prevalent in acute hospital populations. Delirium has noticeable effects on length of hospitalization, cost of care, mortality and morbidity. In addition to these well-established adverse consequences, there is increasing evidence linking delirium and a higher risk of long-term cognitive impairment (LTCI), including dementia. A prior review (Jackson, Gordon, Hart, Hopkins, & Ely, 2004), in which nine studies (total N = 1,885, years 1989-2003) were considered, concluded that there was evidence for an association between delirium and LTCI. Here we provide a review of studies published since Jackson's review. We included nine reports, with a total of 2,025 patients. The studies show diverse sample sizes, methodologies, designs and patient populations. However, taken together, the results of these new studies broadly confirm that there is a link between delirium and LTCI. We go on to discuss putative mechanisms and explanations. These include (1) delirium as a marker of chronic progressive pathology, but unrelated to any progression, (2) delirium as a consequence of acute brain damage which is also responsible for a 'single hit' or triggering of active processes causing LTCI, (3) delirium itself as a cause of LTCI, and (4) drug treatment of delirium or other conditions as a cause of LTCI. We conclude with suggestions for future research.
    • "The literature suggests a reduced quality of life for survivors of critical illness and delirium, and this reinforces the relationships between post‑ICU cognitive impairment and cognitive morbidity and decreased social interaction (Hopkins and Jackson 2009; Stevens and Nyguist 2007; Jackson et al 2003 as cited in Ely et al 2004a Hopkins et al 1999). Nonetheless, data to support these relationships are still limited (MacLullich et al 2009; Girard et al 2008; Gunther et al 2008; Stevens and Nyguist 2007). Expanding investigations on long‑term psychosocial functioning following mechanical ventilation‑related delirium will facilitate better understanding of this neurocognitive sequelae and its impact on cognitive outcomes. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective This paper reviews existing literature on delirium that arises during mechanical ventilation in the Intensive Care Unit (ICU). It looks at the physiology of delirium, its subtypes and risk factors. It further considers the impact of delirium on cognitive and psychosocial function of patients after their discharge from acute care. The aim of this paper was to increase awareness of ICU delirium, accentuate the potential link between different sedation agents and the development of delirium, and inform practitioners, especially nurses, about this common neurocognitive disorder that appears in the Intensive Care Unit (ICU). Setting Intensive Care Unit (of any acute hospital) where is ICU located. Subjects Mechanically ventilated patients. Primary argument This paper argues for the awareness of delirium in the Intensive Care Unit and examines sedation during mechanical ventilation with its potential role in promoting this disorder. Conclusion Delirium is the most common neurobehavioral disorder in patients who are critically ill and mechanically ventilated in ICU. It frequently generates psychiatric and psychological outcomes such as depressed mood, anxiety and/or Post Traumatic Stress Disorder (PTSD). Cognitive and psychological dysfunction following delirium seems to be overlooked, under recognised, and misdiagnosed in the ICU. These impairments are often incorrectly attributed to other processes, such as concurrent psychoactive medication use, substance use, or psychiatric disorders, in particular depression, rather than delirium. Although it is generally accepted that providing sedation for a patient’s comfort is an essential part of bedside care for nearly every patient in ICU, an increasing number of researchers hypothesise there is a strong link between sedation practice and long-term patient centred outcomes, such as quality of life (Dimopoulou et al 2004) and cognitive and psychosocial functioning. Increasing nurses’ awareness of this potential link is exceptionally important, as they are instrumental in administration and observing subsequent side effects of any medication, including sedatives.
    Full-text · Article · Sep 2015
    • "High concentrations of pro-inflammatory mediators released by M1 activated microglia are potentially neurotoxic and might not only cause acute, reversible, behavioral effects, such as delirium, but also lead to persistent detrimental effects through bystander damage to neighboring neurons [16, 17]. The microglial response drifts out of control and ultimately causes neurodegeneration [1, 18]. This cycle might account for why neurobehavioral occurrences can persist in elderly patients after recovery from sepsis and after systemic cytokine production has fallen. "
    [Show abstract] [Hide abstract] ABSTRACT: Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role of microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain. We searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions. Fifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels. Animal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.
    Full-text · Article · Jun 2015
    • "Despite its common occurrence, the pathophysiology of delirium remains poorly understood. A number of mechanisms have been proposed, mainly emphasizing neurotransmission , inflammation, and chronic stress234. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that attracts leukocytes of the monocyte lineage [5]. Within the CNS, MCP-1 is produced mainly by astrocytes and resident microglia, and MCP-1 overexpression has been associated with neuroinflammatory conditions like multiple sclerosis, stroke and Alzheimer's disease [6]. "
    [Show abstract] [Hide abstract] ABSTRACT: Delirium is common, associated with poor outcome, but its pathophysiology remains obscure. The aim of the present study was to study a possible role of monocyte chemoattractant protein-1 (MCP-1) in the development of delirium. A prospective cohort of 19 hip fracture patients (median age 83 years) were screened for delirium daily by validated methods. MCP-1 was measured on arrival and postoperatively. The number of patients with a raise in MCP-1 was statistically significantly higher in the group with delirium in the postoperative phase compared to the no-delirium group (5/6 vs. 1/7, p = .03). MCP-1 might play a role in the development of delirium.
    Full-text · Article · May 2015
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