2014 Delirium in Elderly People
2014 Delirium in Elderly People
2014 Delirium in Elderly People
Delirium is an acute disorder of attention and cognition in elderly people (ie, those aged 65 years or older) that is Published Online
common, serious, costly, under-recognised, and often fatal. A formal cognitive assessment and history of acute onset August 28, 2013
http://dx.doi.org/10.1016/
of symptoms are necessary for diagnosis. In view of the complex multifactorial causes of delirium, multicomponent S0140-6736(13)60688-1
non-pharmacological risk factor approaches are the most effective strategy for prevention. No convincing evidence Department of Medicine, Beth
shows that pharmacological prevention or treatment is effective. Drug reduction for sedation and analgesia and non- Israel Deaconess Medical
pharmacological approaches are recommended. Delirium offers opportunities to elucidate brain pathophysiology— Center, Harvard Medical
it serves both as a marker of brain vulnerability with decreased reserve and as a potential mechanism for permanent School, Boston, MA, USA
(Prof S K Inouye MD); Aging
cognitive damage. As a potent indicator of patients’ safety, delirium provides a target for system-wide process Brain Center, Institute for
improvements. Public health priorities include improvements in coding, reimbursement from insurers, and research Aging Research, Hebrew
funding, and widespread education for clinicians and the public about the importance of delirium. SeniorLife, Boston, MA, USA
(Prof S K Inouye); Leiden
University Medical Center,
Introduction Leiden, Netherlands
Despite first being described more than 2500 years ago, Epidemiology (STROBE) criteria for setting, participants, (Prof R G J Westendorp MD);
delirium remains frequently unrecognised and poorly measurement, and statistical methods,13 and use of a Leyden Academy on Vitality
understood. Delirium—an acute decline in cognitive validated delirium instrument. We chose this timeframe and Ageing, Leiden,
Netherlands
functioning—is a common, serious, and often-fatal to update information gathered for a previous (Prof R G J Westendorp); and
disorder that affects as much as 50% of elderly people (ie, comprehensive review.14 An additional inclusion criterion Division of Geriatric Medicine
those aged 65 years or older) in hospital, and costs more for incidence studies was serial delirium assessments and Meyers Primary Care
Institute, University of
than US$164 billion per year in the USA1 and more than with intervals of no longer than 3 days by trained research
Massachusetts Medical School,
$182 billion per year2,3 in 18 European countries combined staff or clinicians. Table 1 presents the prevalence rates Worcester, MA, USA
(2011 estimates; appendix). Delirium is preventable (present on admission) and incidence rates (new onset) (J S Saczynski PhD)
in 30–40% of cases,4,5 and thus holds substantial public of delirium across different populations as described Correspondence to:
health relevance as a target for interventions to prevent in 35 selected studies (appendix). The sum of prevalence Dr Sharon K Inouye, Aging Brain
the associated burden of downstream complications and and incidence yields the overall occurrence rate in each Center, Institute for Aging
Research, Hebrew
costs.6 Accordingly, delirium is now included on patients’ setting. The highest incidence rates were noted in SeniorLife, 1200 Centre Street,
safety agendas7 and has been increasingly used as an intensive-care unit ICU and in postoperative and Boston, MA 02131, USA
indicator of health-care quality for elderly people.8,9 palliative care settings. Because many of these 35 studies agingbraincenter@hsl.harvard.
Delirium can be thought of as acute brain failure—ie, a excluded patients with cognitive impairment or dementia edu
multifactorial syndrome analogous to acute heart at baseline, true incidence is probably underestimated.
failure—and might provide a novel approach to In general medical and old age medicine wards, the See Online for appendix
elucidation of brain functioning and pathophysiology. prevalence of delirium (present on admission) of 18–35%
Delirium can have acute onset in response to noxious should be added to the incidences, yielding an overall
insults (such as major surgery or sepsis), and might help occurrence in these settings of 29–64% (table 1). The
to shed light on cognitive reserve—ie, the brain’s prevalence of delirium in the community is low (1–2%),
resilience to external factors.10 In this context, delirium but onset usually brings the patient to emergency care.
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, Search strategy and selection criteria
but rather a series of punctuated declines and recoveries We comprehensively searched Medline, PubMed, and reference lists from relevant original
in the face of delirium and major medical insults.11,12 articles and systematic reviews (appendix) with the terms “delirium”, “acute confusion”, and
Furthermore, accumulating evidence suggests that “organic brain syndrome” for papers published in English between Jan 1, 1990, and Aug 31,
delirium itself might lead to permanent cognitive decline 2012. To provide an overview of epidemiology, causes, and non-pharmacological and
and dementia in some patients. We provide a state-of-the- pharmacological management of delirium, we reviewed work published between Jan 1,
art review of delirium to guide clinical practice and 2004, and Dec 31, 2012, to update a previous comprehensive review, with the exceptions of
elucidate important topics for future research. validated risk prediction models and non-pharmacological studies, for which we expanded
our search to include original articles published between Jan 1, 1990, and Dec 31, 2012. All
Epidemiology data presented are taken from original papers, and we did not do meta-analyses. The
On the basis of a systematic review of medical literature pathophysiology search used the same search terms with the addition of “etiology”,
published between Jan 1, 2004, and Aug 31, 2012, we “pathophysiology”, “physiopathology”, or “pathogenesis”. Our goal was to provide a
selected articles about the incidence and outcomes of comprehensive review of primary articles, and thus systematic reviews and meta-analyses
delirium by the following criteria: sample size of 100 or were not routinely included; however, we checked the reference lists of such papers to
more, prospective sampling framework, satisfaction of ensure the comprehensive inclusion of primary articles in our review process (appendix).
Strengthening the Reporting of OBservational Studies in
Actions
Assessment
History Check baseline cognitive function and recent (within past 2 weeks) changes in mental status (eg, family, staff)
Recent changes in disorder, new diagnoses, complete review of systems
Review all current drugs (including over-the-counter and herbal preparations); pay special attention to new
drugs and drug interactions
Review alcohol and sedative use
Assess for pain and discomfort (eg, urinary retention, constipation, thirst)
Vital signs Measure temperature, oxygen saturation, fingerstick glucose concentration
Take postural vital signs as needed
Physical and neurological examination Search for signs of occult infection, dehydration, acute abdominal pain, deep vein thrombosis, other acute
illness; assess for sensory impairments
Search for focal neurological changes and meningeal signs
Targeted laboratory assessment Consider full blood count; urinalysis; measurement of concentrations of electrolyres, calcium, and glucose;
(selected tests based on clues from history measurement of renal, liver, and thyroid function; taking cultures of urine, blood, sputum; measurement of
and physical)* drug concentrations; measurement of concentrations of ammonia, vitamin B12, and cortisol
Measure arterial blood gas
Do electrocardiography
Chest radiography
Lumbar puncture should be reserved for assessment of fever with headache and meningeal signs or suspicion
of encephalitis
Targeted neuroimaging (selected patients) Assess focal neurological changes (stroke can present as delirium)
Test for suspected encephalitis (for temporal lobe changes)
Assess patients with histories or signs of head trauma
Electroencephalography Assess for occult seizures
(selected patients) Differentiate psychiatric disorder from delirium
Management
Drug adjustments Reduce or remove psychoactive drugs (eg, anticholinergics, sedatives or hypnotics, opioids); lower dosages;
avoid as required dosing
Substitute less toxic alternatives
Use non-pharmacological approaches for sleep and anxiety, including music, massage, relaxation techniques
Address acute medical issues Treat problems identified in work-up (eg, infection, metabolic disorders)
Maintain hydration and nutrition
Treat hypoxia
Reorientation strategies Encourage family involvement; use companions as needed
Address sensory impairment; provide eyeglasses, hearing aids, interpreters
Maintain safe mobility Avoid use of physical restraints, tethers, and bed alarms
Ambulate patient at least three times per day; active range-of-motion
Encourage self-care and regular communication
Normalise sleep–wake cycle Discourage napping and encourage exposure to bright light during the day
Try to provide uninterrupted period for sleep at night
Provide non-pharmacological sleep protocol and quiet room at night with low level lighting
Pharmacological management Reserve for patients with severe agitation that interrupts essential treatment (eg, intubation) or severe
psychotic symptoms
Start with low doses and titrate until effect achieved; haloperidol 0·25–0·5 mg orally or intramuscularly twice a
day is preferred; atypical antipsychotics close in effectiveness
*Not all of these tests should be done in all patients; rather, specific tests should be guided by history, physical examination, and previous results.
family and informal caregivers, and could help with early tests, such as the short portable mental status
recognition of delirium.80 questionnaire,81 the mini-cog,82 or the Montreal cognitive
assessment,83 should be done. When time is very scarce,
Assessment and work-up assessment of orientation and an attention task, such as
The most important step is establishment of the naming of days of the week (no errors should be allowed)
diagnosis of delirium by obtaining a history from an or months of the year (one error should be allowed)
informed observer (eg, family member, caregiver, or staff backwards, serial sevens (one error should be allowed for
member) and doing a brief cognitive assessment. To five subtractions), or recitation of digit spans (normally
differentiate delirium from dementia, an accurate history three or more) backwards can substitute for basic
is crucial to establish the patient’s baseline and acuity of screening. These cognitive tests are needed to establish if
mental status change, to recognise the fluctuations in the patient fulfils criteria for delirium.
cognition and other symptoms typical of delirium, and to In view of the high rates of adverse outcomes and
identify possible causes. Formal cognitive screening mortality, any suspected or uncertain cases (including
patients with lethargy or those who are unable to For initial symptom management, non-pharma-
complete an interview) should be treated as delirium cological approaches are the first-line strategy and include
until proven otherwise. Initial management has three discontinuation or dose reduction of anticholinergic and
simultaneous priorities—specifically, maintenance of the psychoactive drugs, family or companion involvement for
patient’s safety, identification of the cause or causes, and reorientation and comfort, non-pharmacological
management of symptoms. In terms of safety, efforts approaches to sleep and relaxation (eg, a glass of warm
should focus on protection of the airway and prevention milk or herbal tea, relaxation music, back rubs),93 creation
of aspiration, maintenance of hydration and nutrition, of a quiet, soothing, warm environment, and pain
prevention of skin breakdown, and provision of safe management. Drugs should be used only in severely
mobility while preventing falls. Restraints and bed agitated patients in whom interruption of essential
alarms increase risk and persistence of delirium and medical therapies (eg, mechanical ventilation, dialysis
injury and should be avoided.84,85 catheters) or self-harm is a risk, or in patients with
Table 4 summarises the suggested work-up and initial extremely distressing psychotic symptoms (eg,
management of delirium. Several fundamental points hallucinations, delusions).
should be emphasised. First, delirium can be the
harbinger of a medical emergency, and thus all patients Non-pharmacological prevention and treatment
presenting with delirium should be screened for acute Primary prevention with non-pharmacological
physiological disturbances—eg, hypoxaemia, hypo- multicomponent approaches is widely accepted as the
glycaemia, and high arterial carbon dioxide concentra- most effective strategy for delirium.6,14,67 The appendix
tions. Second, the disease can have occult or atypical lists non-pharmacological approaches from 13 studies,
presentation in older people—eg, in octogenarians, each of which included 25 or more patients in both
myocardial infarction presents more often as delirium intervention and control groups, applied a prospective
than as the classic presentation of chest pain or shortness sampling framework, included a validated delirium
of breath. Thus, a family member’s non-specific assessment, and achieved a modified Jadad (0–6) score94
complaint that the patient is not himself or herself of at least 4 points. Two reviewers rated each article
should never be taken lightly. Third, diagnostic independently and reached consensus.
assessments (eg, laboratory testing, neuroimaging) The most widely disseminated approach is the Hospital
should be targeted on the basis of the patient’s history Elder Life Program (HELP),4,95,96 a multicomponent
and physical examination—untargeted testing will intervention strategy with proven effectiveness and cost-
probably have low yields.86 effectiveness in the prevention of delirium and functional
Electroencephalography (EEG) has little sensitivity and decline97,98 through targeting of risk factors for delirium.
specificity in the diagnosis of delirium. However, delirium The interventions include reorientation, therapeutic
does have a characteristic pattern of diffuse slowing with activities, reduced use and doses of psychoactive drugs,
increased theta and delta activity and poor organisation of early mobilisation, promotion of sleep, maintenance of
background rhythm, which correlates with severity of adequate hydration and nutrition, and provision of vision
delirium. EEG can be particularly useful in the and hearing adaptations. The programme should be
differentiation of organic causes from functional or implemented by a skilled interdisciplinary team, who
psychiatric disorders in difficult-to-assess patients, should be assisted by either nursing staff or trained
assessment of deteriorating mental status in patients volunteers. Although originally assessed in a large-scale
with dementia, and identification of occult seizures (eg, controlled clinical trial, more than ten follow-up studies
non-convulsive status epilepticus, atypical complex partial have shown that the programme is effective in diverse
seizures).87,88 Quantitative and spectral EEG might be of settings and populations.99–101 HELP is now implemented
use in assessments of delirium, but their performance in more than 200 hospitals worldwide, but adaptations
characteristics need further investigation. Neuroimaging, and alternatives may be necessary in some settings
including non-contrast head CT and MRI, is low yield in because of resource constraints or poor availability of
unselected patients. It is recommended to assess acute skilled interdisciplinary old age medicine professionals.
focal neurological findings (because patients with strokes Factors crucial to initiate and sustain the programme are
or haemorrhages can present with delirium) and in internal support, effective champions, programme
patients with a history or signs of recent fall or head fidelity while adapting to local circumstances,
trauma, fever and suspected encephalitis, or decreased documentation of positive outcomes, and long-term
consciousness of unidentified cause.89,90 Brain scans are funding and resources.102,103 Savings of roughly $9000 per
normal in more than 98% of patients whose delirium has patient per year have been estimated.1,98,101
an identified medical cause or who have pre-existing Proactive old age medicine consultation is another
dementia.91 Lumbar puncture should be considered92 successful approach that has been assessed in a
when meningitis, encephalitis, or subarachnoid randomised controlled trial.5 Old age medicine specialists
hemorrhage is suspected, and might be indicated when make recommendations before and after surgery on the
delirium is persistent or no cause can be identified. basis of ten structured modules, including hydration,
pain management, nutrition, and mobilisation. The delirium have been identified, but the fundamental
success of this strategy, however, is integrally linked to pathophysiological basis remains obscure. Important
adherence to his or her recommendations. knowledge gaps need to be addressed.
Other non-pharmacological interventions that have
been studied (appendix) include multifactorial targeted Delirium and dementia
interventions, delirium screening and intervention on Is delirium simply a marker of vulnerability to dementia,
old age medicine units, staff training or educational or does delirium itself lead to dementia? This question is
programmes, and interdisciplinary consultation. the subject of much controversy, but ultimately both
Approaches in the past 6 years have included hypotheses are probably true. An episode of delirium can
interventions delivered by family members and mobility signal vulnerability of the brain, with decreased cognitive
or rehabilitation interventions, both of which are reserve and increased risk for future dementia, and
effective in the prevention of delirium. The use of delirium can bring previously unrecognised cognitive
earplugs at night was moderately efficacious in an impairment to medical attention. Delirium and dementia
ICU-based trial,104 and might be a useful adjunct to non- frequently coexist, and dementia is a leading risk factor for
pharmacological sleep protocols.93 Delirium rooms105— delirium (table 2). Furthermore, a growing body of
spaces that provide restraint-free care for patients with evidence, ranging from epidemiological studies to tissue
delirium, are staffed with specially trained nurses, and culture and animal studies, suggests that delirium leads to
promote non-pharmacological management approach- permanent cognitive impairment and dementia. A 2010
es—are an intriguing idea for provision of specialised meta-analysis107 of two studies (total n=241) showed that
management for patients with delirium, but have not yet delirium was associated with an increased rate of incident
been assessed in a controlled trial. Many studies of non- dementia (adjusted relative risk, 5·7, 95% CI 1·3–24·0).
pharmacological approaches have been hampered by In a sample of 225 cardiac surgery patients,12 delirium was
issues such as an absence of comparator groups or of associated with a severe punctuated decline in cognitive
prospective balanced allocation to study groups, or functioning, followed by recovery during 6–12 months in
unmasked assessment of outcomes. most patients. However, a substantial proportion of
patients, particularly those with prolonged delirium, never
Pharmacological prevention and treatment regained their baseline cognitive level. In 263 patients
The appendix lists 16 studies of pharmacological with Alzheimer’s disease,30 delirium was associated with a
approaches to delirium prevention and treatment that doubling of the rate of cognitive decline during the year
included at least 25 patients in both the intervention and after hospital admission and accelerated decline persisting
control groups, applied a prospective sampling during 5 years’ follow-up.
framework, included a validated delirium assessment, Further evidence supports a direct role for delirium in
and achieved a modified Jadad score94 of at least 4 points. dementia. In an important study of 553 people who were
No convincing, reproducible evidence of effectiveness has aged 85 years or older at baseline,58 the findings of which
been reported for any of these treatments. In six of the were neuropathologically confirmed, delirium in-
trials, rates of delirium did not differ significantly between creased the risk of incident dementia (odds
groups. In eight of the trials, treatment reduced delirium ratio 8·7, 95% CI 2·1–35·0). Alzheimer’s pathology was
rates but this reduction either had no effect on clinical significantly associated with dementia in patients without
outcomes (such as ICU admission, length of hospital delirium, whereas no such relationship was noted in
stay, complications, or mortality) or clinical outcomes those with delirium, suggesting alternative pathological
were not measured. In two trials, treatment resulted in mechanisms for dementia after delirium. This study was
potentially worse outcomes compared with placebo. limited, however, by a high rate of loss to follow-up.
Olanzapine reduced the incidence but increased the Previous studies in animal models and human
duration and severity of delirium (without reported neuronal cell cultures have shown that exposure to
clinical outcomes), and rivastigmine resulted in increased inhaled anaesthetics can induce neurotoxic effects,
duration and mortality. Different approaches were used including apoptosis, caspase activation, Aβ
to assess delirium in all 16 trials, and the populations oligomerisation and accumulation, neuroinflammation,
investigated were diverse. Thus, to generalise findings is and mitochondrial dysfunction.108,109 Preliminary results
difficult. Because of the preponderance of evidence, in human beings110 suggest that some inhaled
however, pharmacological approaches to prevention and anaesthetics (eg, isoflurane) might be more neurotoxic
treatment are not recommended at this time.6,106 than others. Important work111 in animal models of
delirium has shown that, in vulnerable animals, systemic
Controversies inflammatory insults can cause punctuated cognitive
Need for increased research decline typical of delirium, followed by acceleration in
Although delirium research has expanded greatly in the disease progression typical of dementia. Furthermore, a
past 30 years, many key aspects of the disorder remain dose of lipopolysaccharide, which induces an
poorly understood. Some biomarkers associated with inflammatory insult similar to that induced by a
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