Continuing Medical Education online delirium should still be used as the standard term for
this syndrome.2 Over time, the term delirium has evolved
This activity has been planned and implemented in accordance
with the essential Areas and policies of the Accreditation to describe a transient, reversible syndrome that is acute
Council for Continuing Medical education (CMe) through the joint and fluctuating, and which occurs in the setting of a
sponsorship of Medscape, LLC and Nature Publishing Group. medical condition.
Medscape, LLC is accredited by the Accreditation Council for Clinical experience and recent research have shown
Continuing Medical education (ACCMe) to provide continuing that delirium can become chronic or result in perma-
medical education for physicians.
nent sequelae. In elderly individuals, delirium can initiate
Medscape, LLC designates this educational activity for a maximum
of 1.0 AMA PRA Category 1 CreditsTM. Physicians should only claim
or otherwise be a key component in a cascade of events
credit commensurate with the extent of their participation in the that lead to a downward spiral of functional decline, loss
activity. All other clinicians completing this activity will be issued of independence, institutionalization, and, ultimately,
a certificate of participation. To participate in this journal CMe death. Delirium affects an estimated 1456% of all hos-
activity: (1) review the learning objectives and author disclosures;
(2) study the education content; (3) take the post-test and/or
pitalized elderly patients. At least 20% of the 12.5 million
complete the evaluation at http://cme.medscape.com/public/ patients over 65 years of age hospitalized each year in
naturereviews; and (4) view/print certificate. the US experience complications during hospitalization
Learning objectives because of delirium.35
Upon completion of this activity, participants should be able to: The aims of this report are to review the current clini-
1 Define the term delirium. cal practice in delirium, focusing particularly on elderly
2 Describe the prevalence of delirium in hospitalized elderly individuals. The topics covered include epidemiology,
patients.
clinical features, differential diagnosis, treatment, preven-
3 identify risk factors for delirium in the elderly.
4 recognize neuroimaging findings seen in delirium. tion and outcome. The economic impact of delirium is
5 Describe ways to prevent delirium in the hospital. discussed. Potential pathological mechanisms, including
evidence from neuroimaging studies, are also examined.
Finally, future avenues of research are highlighted.
Aging Brain Center, Introduction
institute for Aging Delirium is a common clinical syndrome characterized Epidemiology
research,
Hebrew seniorLife, by inattention and acute cognitive dysfunction. The word The overall prevalence of delirium in the community is
Boston, MA, UsA delirium was first used as a medical term as early as the just 12%, but in the setting of general hospital admis-
(TG Fong, SR Tulebaev,
SK Inouye). first century AD to describe mental disorders occurring sion this increases to 1424%. The incidence of delirium
during fever or head trauma.1 A diverse range of terms arising during a hospital stay ranges from 6% to as high
Correspondence: has since emerged to describe delirium, including acute as 56%,6 and this incidence is even higher when more-
TG Fong, Aging Brain
Center, institute for confusional state, acute brain syndrome, acute cerebral specialized populations are considered, including those
Aging research, insufficiency and toxicmetabolic enkephalopathy, but in postoperative, intensive-care, subacute and palliative-
Hebrew seniorLife,
1200 Center street, care settings.79 Postoperative delirium occurs in 1553%
Boston, MA 02131, of surgical patients over the age of 65 years,10 and among
UsA Competing interests
tfong@ The authors, the Journal editor H wood and the CMe questions elderly patients admitted to an intensive care unit (ICU)
bidmc.harvard.edu author D Lie declared no competing interests. the delirium incidence can reach 7087%.11
patients with hypoactive delirium present with lethargy Box 2 | Diagnostic criteria for delirium
and sedation, respond slowly to questioning, and show
little spontaneous movement. The hypoactive form occurs The following criteria are derived from the Diagnostic and Statistical Manual
of Mental Disorders, 4th edn, text revision (DsM-iv-Tr; American Psychiatric
most frequently in elderly patients, and these patients are
Publishing, inc., Arlington, vA). All four criteria (AD) are required to confirm a
frequently overlooked or misdiagnosed as having depres- diagnosis of delirium.
sion or a form of dementia. Patients with mixed delirium
demonstrate both hyperactive and hypoactive features. It General diagnostic criteria
has been suggested that each delirium subtype can result (A) Disturbance of consciousness (that is, reduced clarity of awareness of the
from a different pathophysiological mechanism, and that environment) with reduced ability to focus, sustain, or shift attention
each might carry a different prognosis. (B) A change in cognition (such as memory deficit, disorientation, language
Postoperative delirium can develop on the first or disturbance) or the development of a perceptual disturbance that is not better
accounted for by a pre-existing, established, or evolving dementia
second postoperative day, but the condition is often
hypoactive and might, therefore, go unnoticed. Delirium (C) The disturbance develops over a short period of time (usually hours to days)
can be difficult to recognize in the ICU, as standard and tends to fluctuate during the course of the day
cognitive tests of attention often cannot be used in this For delirium due to a general medical condition
setting because patients are intubated and cannot answer (D) evidence from the history, physical examination, or laboratory findings
questions verbally. However, alternative strategies are indicates that the disturbance is caused by the direct physiological
available for testing in this situation (see below). consequences of a general medical condition
trained interviewers.52 In a recent meta-analysis in 1,071 of episodes and days of delirium in hospitalized elderly
patients, the CAm had a sensitivity of 94% and a speci- individuals.56 Proactive geriatric consultation has been
ficity of 89%.53 The performance of the CAm might be found to reduce the risk of delirium following acute hip
compromised, however, if it is used without formal cogni- fracture by 40%.57 Other controlled trials testing delirium
tive testing or by untrained interviewers. Once delirium interventions found that multifactorial interventions or
is identified, the memorial Delirium Assessment Scale, educational strategies targeted towards health-care staff
a 10-item rating scale, can be used to quantify delirium can reduce delirium rates and/or duration.56 A recent con-
severity.54 Other commonly used delirium screening trolled trial also found that home rehabilitation after acute
and severity measures are summarized in Table 2. hospitalization in elderly individuals was associated with
a lower risk of delirium, and greater patient satisfaction,
Management when compared with the inpatient hospital setting.58
Prevention strategies recent studies have examined the role of pharmaco-
An estimated 3040% of cases of delirium are preventable,7 logical strategies in delirium prophylaxis. Haloperidol
and prevention is the most effective strategy for mini- has been shown to reduce the incidence of delirium in a
mizing the occurrence of delirium and its adverse out- small group of patients who underwent surgery.59 This
comes. Drugs such as benzodiazepines or anticholinergics reduction in incidence was not confirmed statistically in
and other known precipitants of delirium should gener- a larger study,60 but haloperidol did reduce the severity
ally be avoided. In addition, benzodiazepine or alcohol and duration of delirium and length of hospital stay in
withdrawal is a common preventable cause of delirium. some patients without causing notable adverse effects.
The Hospital elder life Program (HelP)55 is an inno- Owing to methodological limitations and small sample
vative strategy of hospital care for elderly patients that sizes, these results need to be confirmed before halo-
uses tested delirium prevention strategies to improve peridol can be recommended for routine prophylaxis.
overall quality of hospital care. This program includes The few randomized, controlled clinical trials of cho-
the following: maintaining orientation to surroundings; linesterase inhibitors that have been performed to date
meeting needs for nutrition, fluids and sleep; promoting have shown no benefit for these drugs in the prevention
mobility within the limitations of physical condition; and of postoperative delirium, but these studies were small
providing visual and hearing adaptations for patients with and underpowered.61,62 Several case reports and one
sensory impairments. In a controlled trial that evaluated open-label study have suggested promising results with
HelP, delirium developed in 9.9% of the intervention this approach,6366 but additional randomized, controlled
group, compared with 15.0% of the usual-care group studies of cholinesterase inhibitors in acute medical and
(matched odds ratio 0.60, 95% CI 0.390.92). The HelP critical care populations, as well as the use of these drugs
interventions can also effectively reduce the total number in combination with antipsychotics, are warranted before
any definitive recommendations can be made.67 Other in delirium,7074 but the use of such supportive mea-
strategies that minimize the use of opioids or benzodiaz- sures has nevertheless become standard practice on the
epines through the use of alternative agents such as gaba- basis of clinical experience, common sense, and lack of
pentin68 or dexmedetomidine69 are under investigation adverse effects.75
for their capacity to reduce the incidence of delirium. To minimize the use of psychoactive medications, a
nonpharmacological sleep protocol should be used. This
Treatment strategies protocol includes three components: first, a glass of warm
Nonpharmacological acute treatment strategies milk or herbal tea; second, relaxation tapes or relaxing
nonpharmacological strategies are the first-line treatments music; and third, back massage. This protocol has been
for all patients with delirium. The nonpharmacological demonstrated to be both feasible and effective, and, in
approaches available include reorientation and behavioral one study, implementation of this strategy reduced the
intervention. Caregivers should use clear instructions and use of sleeping medications from 54% to 31% (P <0.002)
make frequent eye contact with patients. Sensory impair- in a hospital environment.76 This intervention strategy is
ments, such as vision and hearing loss, should be mini- part of a multicomponent prevention strategy that has
mized by use of equipment such as spectacles or hearing been demonstrated to be effective.76,77
aids. Physical restraints should be avoided because they
lead to decreased mobility, increased agitation, greater risk Pharmacological strategies
of injury, and prolongation of delirium. Other environ- A systematic review of acute drug treatments for delirium
mental interventions include limiting room and staff indicated that few high-quality, randomized, controlled
changes and providing a quiet patient-care setting, with trials have been performed to date,67 and current clinical
low-level lighting at night. An environment with minimal practice is, therefore, based largely on case series and
noise allows an uninterrupted period of sleep at night and retrospective reports.78,79 medications (Table 3) are usually
is of crucial importance in the management of delirium. reserved for patients in whom the symptoms of delirium
Only a limited number of trials have examined the efficacy might compromise safety or prevent necessary medical
of cognitive, emotional and environmental interventions treatment (that is, those with hyperactive delirium). Some
clinicians advocate the use of drugs for the treatment of with delirium, with controlled trials showing efficacy at
hypoactive delirium, although this approach remains con- least comparable to haloperidol.8284 However, no data
troversial. Given that patients with hypoactive delirium are available to demonstrate any verifiable advantage
can experience distress, such treatment might be war- of one antipsychotic over another. 67 Furthermore, the
ranted. Some data indicate that treatment efficacy or even antipsychotics, including the atypicals and parenteral
treatment choice might vary according to the delirium haloperidol, carry an increased risk of stroke in elderly
subtype,80 and this is an area that requires further study. patients with dementia and can result in prolongation of
A particular challenge that is inherent to drug trials in the QT interval.85
delirium is the evaluation of drug efficacy in the setting Other potential treatments for delirium include cho-
of a fluctuating course and simultaneous treatment of linesterase inhibitors (for example, donepezil), and 5-HT
underlying risk factors.67 receptor antagonists (for example, trazodone). Several
The use of almost any medication to treat behavioral case reports and one open-label study have suggested
changes might further cloud the patients mental status promising results with cholinesterase inhibitors in the
and obscure efforts to monitor the course of the mental treatment of delirium,6366 but additional randomized,
status change, and should, therefore, be avoided if pos- controlled studies of these agents in acute medical and
sible. Any drug chosen to treat delirium should be ini- critical care populations, and of their use in combination
tiated at the lowest starting dose for the shortest time with antipsychotics, are warranted before any definitive
possible. In general, neuroleptics are the preferred agents recommendations can be made.67 Benzodiazepines, such
for the treatment for acute agitation. Haloperidol has as lorazepam, are not recommended as first-line agents in
been the most widely used neuroleptic in this context, the treatment of delirium, because they often exacerbate
and the effectiveness of this drug has been established in mental status changes and cause oversedation.
randomized, controlled clinical trials.81,82 This agent also
has the advantage of being available in parenteral form. Outcomes
Haloperidol is, however, associated with a higher rate The occurrence of delirium, which can result from mul-
of extrapyramidal side effects and acute dystonias than tiple and diverse etiologies, can contribute to poor patient
are atypical antipsychotics. Some atypical antipsychotics outcome, irrespective of the underlying cause. The
(for example, risperidone, olanzapine and quetiapine) agitation and lethargy that can occur in delirium increase
have been used clinically to treat agitation in patients the risk of complications, including aspiration, pressure
ulcers, pulmonary emboli, and decreased oral intake, and Long-term cognitive Full recovery Functional impairment
it has been shown that delirium is associated with infe- impairment
rior outcomes even after controlling for baseline patient
characteristics and etiological factors.86 Also, the more
severe the episode of delirium, the poorer the outcome.87
The outcomes of delirium are summarized in Figure 2. Psychological stress Outcomes of delirium Increased costs
to establish whether the risk of delirium is influenced by it is not yet clear whether delirium leads to permanent
genetic factors, cognitive and/or brain reserve, or even neurological injury that can be measured with laboratory,
pre-existing brain abnormalities, such as atrophy or white electrophysiological or neuroimaging markers.
matter disease. Delirium is a serious cause and complication of
From a pathophysiological perspective, it would be hospitalization in elderly patients and should be con-
interesting to determine, in view of the association between sidered to be a medical emergency until proven other-
dementia and delirium, whether the degree of amyloid wise. Irrespective of the specific etiology, this condition
pathology correlates with the risk of delirium or the likeli- has the potential to markedly affect the overall outcome
hood of recovery from delirium. As mentioned above, the and prognosis of severely ill patients, as well as sub-
potential roles of inflammation and impaired cholinergic stantially increasing health-care utilization and costs. For
neurotransmission, and the interactions between these these reasons, prevention, early recognition and effective
two factors, need further exploration. Also, it will be essen- treatment of delirium are essential.
tial to determine the underlying pathophysiology in order
to explain the diversity in delirium presentation, so as to
advance the diagnosis and treatment of delirium. Review criteria
with regard to treatment, current data support the
use of antipsychotics and nonpharmacological treat- A comprehensive literature review was performed in
ment protocols. However, it will be necessary to conduct PubMed (19902008), using the keyword delirium
in combination with one other search term to review
further randomized trials to evaluate other prevention
major areas including the following: epidemiology,
and treatment strategies in multiple populations, strati- clinical features, pathogenesis, acetylcholine,
fied according to delirium subtype, associated comorbid dopamine, inflammation, neuroimaging, evaluation,
dementia, or risk. treatment and prevention. Only original articles in
Several issues relating to outcomes also need to be clari- the english language were included. The Hospital elder
fied. For example, there is evidence for long-term effects Life Program (HeLP) website bibliography (http://www.
on cognition following delirium, but how often this leads hospitalelderlifeprogram.org), a comprehensive reference
to permanent cognitive impairment, including mild resource on delirium, was also searched for relevant
articles on delirium.
cognitive impairment or dementia, is still not known. Also,
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