We comprehensively searched Medline, PubMed, and reference lists from relevant original articles and systematic reviews (appendix) with the terms “delirium”, “acute confusion”, and “organic brain syndrome” for papers published in English between Jan 1, 1990, and Aug 31, 2012. To provide an overview of epidemiology, causes, and non-pharmacological and pharmacological management of delirium, we reviewed work published between Jan 1, 2004, and Dec 31, 2012, to update a previous comprehensive
ReviewDelirium in elderly people
Introduction
Despite first being described more than 2500 years ago, delirium remains frequently unrecognised and poorly understood. Delirium—an acute decline in cognitive functioning—is a common, serious, and often-fatal disorder that affects as much as 50% of elderly people (ie, those aged 65 years or older) in hospital, and costs more than US$164 billion per year in the USA1 and more than $182 billion per year2, 3 in 18 European countries combined (2011 estimates; appendix). Delirium is preventable in 30–40% of cases,4, 5 and thus holds substantial public health relevance as a target for interventions to prevent the associated burden of downstream complications and costs.6 Accordingly, delirium is now included on patients' safety agendas7 and has been increasingly used as an indicator of health-care quality for elderly people.8, 9
Delirium can be thought of as acute brain failure—ie, a multifactorial syndrome analogous to acute heart failure—and might provide a novel approach to elucidation of brain functioning and pathophysiology. Delirium can have acute onset in response to noxious insults (such as major surgery or sepsis), and might help to shed light on cognitive reserve—ie, the brain's resilience to external factors.10 In this context, delirium could be a marker of the vulnerable brain with diminished reserve capacity. Evidence suggests that the trajectory of normal cognitive ageing might not be a linear decline, but rather a series of punctuated declines and recoveries in the face of delirium and major medical insults.11, 12 Furthermore, accumulating evidence suggests that delirium itself might lead to permanent cognitive decline and dementia in some patients. We provide a state-of-the-art review of delirium to guide clinical practice and elucidate important topics for future research.
Section snippets
Epidemiology
On the basis of a systematic review of medical literature published between Jan 1, 2004, and Aug 31, 2012, we selected articles about the incidence and outcomes of delirium by the following criteria: sample size of 100 or more, prospective sampling framework, satisfaction of Strengthening the Reporting of OBservational Studies in Epidemiology (STROBE) criteria for setting, participants, measurement, and statistical methods,13 and use of a validated delirium instrument. We chose this timeframe
Causes
Although a single factor can lead to delirium, usually delirium is multifactorial in elderly people. The multifactorial model of the cause of delirium has been well validated and widely accepted.31 Development of delirium is dependent on complex inter-relationships between vulnerable patients with several predisposing factors and exposure to noxious insults or precipitating factors (figure). Thus, in vulnerable patients, such as those with underlying dementia and multimorbidity, a seemingly
Pathophysiology
In view of the complex multifactorial causation of delirium, each individual episode probably has a unique set of component contributors; each set represents a discrete yet sufficient causal mechanism. Thus, a single cause or mechanism for delirium will probably not be discovered. Rather, accumulating evidence suggests that several different sets of interacting biological factors result in disruption of large-scale neuronal networks in the brain, leading to acute cognitive dysfunction.33 Some
Diagnosis
Delirium is a clinical diagnosis, which is often unrecognised and easily overlooked. Recognition of the disorder necessitates brief cognitive screening and astute clinical observation. Key diagnostic features include an acute onset and fluctuating course of symptoms, inattention, impaired consciousness, and disturbance of cognition (eg, disorientation, memory impairment, language changes).61, 62 Supportive features include disturbance in sleep–wake cycle, perceptual disturbances (hallucinations
Assessment and work-up
The most important step is establishment of the diagnosis of delirium by obtaining a history from an informed observer (eg, family member, caregiver, or staff member) and doing a brief cognitive assessment. To differentiate delirium from dementia, an accurate history is crucial to establish the patient's baseline and acuity of mental status change, to recognise the fluctuations in cognition and other symptoms typical of delirium, and to identify possible causes. Formal cognitive screening
Non-pharmacological prevention and treatment
Primary prevention with non-pharmacological multicomponent approaches is widely accepted as the most effective strategy for delirium.6, 14, 67 The appendix lists non-pharmacological approaches from 13 studies, each of which included 25 or more patients in both intervention and control groups, applied a prospective sampling framework, included a validated delirium assessment, and achieved a modified Jadad (0–6) score94 of at least 4 points. Two reviewers rated each article independently and
Pharmacological prevention and treatment
The appendix lists 16 studies of pharmacological approaches to delirium prevention and treatment that included at least 25 patients in both the intervention and control groups, applied a prospective sampling framework, included a validated delirium assessment, and achieved a modified Jadad score94 of at least 4 points. No convincing, reproducible evidence of effectiveness has been reported for any of these treatments. In six of the trials, rates of delirium did not differ significantly between
Need for increased research
Although delirium research has expanded greatly in the past 30 years, many key aspects of the disorder remain poorly understood. Some biomarkers associated with delirium have been identified, but the fundamental pathophysiological basis remains obscure. Important knowledge gaps need to be addressed.
Delirium and dementia
Is delirium simply a marker of vulnerability to dementia, or does delirium itself lead to dementia? This question is the subject of much controversy, but ultimately both hypotheses are probably true.
Future directions and recommendations
Although many knowledge gaps remain, available evidence in delirium provides a clear path to move forward. Table 5 outlines some of the research priorities in delirium and the concomitant public health priorities necessary for progress. Each research domain should be coupled with translation into practice and policy to effect change.
Important public health and policy priorities should include more logical coding and insurance-based reimbursement strategies for delirium. At least 11 codes for
Search strategy and selection criteria
References (117)
- et al.
Aging, brain disease, and reserve: implications for delirium
Am J Geriatr Psychiatry
(2010) - et al.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies
Lancet
(2007) - et al.
Incidence and short-term consequences of delirium in critically ill patients: a prospective observational cohort study
Int J Nurs Stud
(2012) - et al.
Postoperative delirium in intensive care patients: risk factors and outcome
Rev Bras Anestesiol
(2012) - et al.
Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses
J Psychosom Res
(2008) Impact of glucocorticoids on brain function: relevance for mood disorders
Psychoneuroendocrinology
(2011)- et al.
Psychotogenic drugs and delirium pathogenesis: the central role of the thalamus
Med Hypotheses
(2005) - et al.
Role of microglia and toll-like receptor 4 in the pathophysiology of delirium
Med Hypotheses
(2012) - et al.
Systemic infection and delirium: when cytokines and acetylcholine collide
Lancet
(2010) - et al.
Cerebrovascular hemodynamics in Alzheimer's disease and vascular dementia: a meta-analysis of transcranial doppler studies
Ageing Res Rev
(2012)