Marisa Wan, MD, FRCPC, Jocelyn M.

Chase, MD, FRCPC

Delirium in older adults:

Diagnosis, prevention, and
treatment
Recognizing delirium promptly and treating the underlying cause
can prevent the significant consequences of an acute disturbance
in cognition, which include cognitive and functional decline, falls,
and admission to long-term care.

ABSTRACT: Delirium is common
in hospitalized older adults and is
known to increase the risk for sub-
sequent functional decline and mor-
tality. The pathophysiology is not
fully understood, but delirium may
be due to inflammatory mechanisms
and a cholinergic neurotransmitter
deficiency in the brain. During acute
illness, older patients are at risk of
delirium due to a decreased cogni-
tive reserve. A high index of suspi-
cion can allow clinicians to recog-
nize delirium promptly and search
for the underlying cause. Workup in-
cludes a thorough history, physical
examination, and investigations to
identify acute illness or destabilized
D
chronic conditions. Therapy focuses
on treating the triggering cause as
well as addressing patient-specific
and environmental risk factors that
may contribute to the development
or worsening of delirium. Ideally,
nonpharmacological strategies
should be used to address six risk
factors that contribute to delirium:
cognitive impairment, sleep depriva-
tion, immobility, visual impairment,
hearing impairment, and dehydra-
tion. While antipsychotics can be
used off-label to manage symptoms
of delirium, they do not treat the un-
derlying cause and are associated
with side effects.
elirium is defined as an acute
decline in cognitive function-
ing and should be considered
a medical emergency as it is often the
result of a noxious disruption to equi-
librium. Delirium is common in the
hospitalized older adult, with some
studies reporting incidence rates of
29% to 64%.1 The consequences of
delirium are significant and include
associations with increased mortality,
cognitive and functional decline, falls,
and admission to long-term care.1
When delirium does occur, the medi-
cal team and patients family should
be aware that further support on dis-
charge may be needed given the risk
of cognitive and functional decline
associated with delirium.
Delirium is considered a quality
indicator in the care of hospitalized
older patients.2 A better understand-
ing of the pathophysiology of deliri-
um and some effective strategies for

Dr Wan is a staff geriatrician at Providence

Health Care. Dr Chase is a clinical instructor
in the Division of Geriatric Medicine at the
University of British Columbia and a staff
This article has been peer reviewed. geriatrician at St. Pauls Hospital.

bc medical journal vol. 59 no. 3, april 2017 bcmj.org 165

 Delirium in older adults: Diagnosis, prevention, and treatment
diagnosis, prevention, and manage-
ment can help clinicians ensure that
patients affected by delirium receive
the care they need.
Risk factors and
pathophysiology
Delirium can arise following one
single destabilizing medical event,
but more often multiple factors con-
tribute to its initiation and develop-
ment. In addition, some patients are
more vulnerable than others. In one
study, Inouye and colleagues identi-
fied the most important preadmission
risk factors for delirium to be visual
impairment, severe illness, cognitive
impairment, and volume depletion.3
The greatest in-hospital risk factors
found in another study were the use
of physical restraints, malnutrition,
polypharmacy, the use of a urinary
catheter, and any iatrogenic event.4
With each additional predisposing
The presence of delirium may indicate
underlying brain vulnerability and
should therefore increase suspicion for
an underlying cognitive impairment or
dementia, especially if the precipitating
insult appears disproportionately minor.
factor, the likelihood of delirium
grows and should prompt a clinician
to consider prevention strategies.
The pathogenesis behind delirium
is not fully understood, but several
mechanisms have been postulated.
Systemic inflammatory cytokine re-
sponse and neurotransmitter disrup-
tion are the two main mechanisms
166 bc medical journal vol. 59 no. 3, april 2017 bcmj.org
thought to link multifactorial medical
conditions and delirium.5 During a
systemic inflammatory response such
as sepsis, proinflammatory cytokines
released in the peripheral circulation
enter the central nervous system, al-
tering endothelial function, diminish-
ing perfusion, activating microglia,
and causing neuronal apoptosis and
neurotoxicity. This process is self-
propelling and can last for months af-
ter the initial event.5
Anticholinergic medications are
known to induce or worsen delirium
by binding to nicotinic and muscarinic
receptors in the brain, modulating cog-
nition and arousal, and lending support
to the concept of cholinergic deficien-
cy in delirium.6 In addition, metabolic
abnormalities may lead to decreased
acetylcholine synthesis and synaptic
transmission. Dopamine, norepineph-
rine, and serotonin can also play a role
in arousal, and their levels are affected
by the cholinergic pathway.6 The func-
tion of other neurotransmitters in de-
lirium, such as glutamate, melatonin,
and gamma-aminobutyric acid, is less
well understood.6
The presence of delirium may in-
dicate underlying brain vulnerability
and should therefore increase suspi-
cion for an underlying cognitive im-
pairment or dementia, especially if
the precipitating insult appears dis-
proportionately minor.7 The patho-
physiological changes described here
also suggest that delirium itself can
cause permanent neuronal damage,
thereby contributing to the risk of
cognitive decline.8 Clinically, it can
take up to 12 months for patients to
return to their cognitive baseline af-
ter an episode of delirium, and some
never regain their previous cognitive
function.9
Diagnosis
One commonly used diagnostic defi-
nition of delirium is based on DSM-5
criteria and requires a new acute
disturbance in cognition, fluctuat-
ing attention, and alteration of the
sleep-wake cycle with changes that
are primarily related to an under-
lying medical cause and not better
explained by an evolving dementia.10
Patients may present with hyperactive
delirium, which is associated with
agitation and hypervigilance, or they
may present with hypoactive deliri-
um, which is associated with drowsi-
ness and apathy. It is not uncommon
for patients to have both forms at
various times during the course of the
same illness. It is particularly easy to
miss a patient with hypoactive delir-
ium as they do not call attention to
themselves, perhaps explaining why
the hypoactive form is associated
with a poorer prognosis.1
The diagnosis of delirium requires
a patient interview, a physical exami-
nation, cognitive testing, and a review
of the medical chart and any collat-
eral information. Screening tools are
an attractive adjunct to clinical as-
sessment, especially if time is lim-
ited. One of the most widely used
is the confusion assessment method
(CAM), validated in various settings,
including intensive care units, emer-
gency departments, and nursing
 Delirium in older adults: Diagnosis, prevention, and treatment
homes, and proven to have high inter
observer reliability.11,12 The abbrevi-
ated 3-minute 3D-CAM, consisting
of clinical observation and a one-
page patient questionnaire, can be
used at the bedside.13 Any assessment
should focus on the main features of
delirium. A diagnosis is suggested by
acute-onset confusion and inattention
plus disordered thinking or altered
level of consciousness. Many hos-
pitals now include a version of the
CAM on nursing assessment flow-
sheets, helping physicians to quickly
scan the chart for signs of delirium.
Because a multitude of underly-
ing causes may be involved, a broad
diagnostic approach is needed and
clinicians should keep an open mind
about the possibility of more than one
contributing medical problem. The
workup should include a detailed as-
sessment to search for the precipitant,
whether it is an acute medical illness,
a change in therapy, or the destabili-
zation of a chronic condition. Causes
of physical discomfort such as con-
stipation and urinary retention are
common precipitants but are often
overlooked. During the physical ex-
amination, the clinician should look
for evidence of occult infection, vol-
ume depletion, abdominal pathology,
deep vein thrombosis, and a neuro-
logical cause.1
The investigations ordered will
depend on the assessment, but gen-
erally include an electrocardiogram,
a complete blood count with differ-
ential, and testing for electrolytes
(including calcium, phosphate, and
magnesium), liver enzymes, thyroid
function, troponin, and vitamin B12.
A chest X-ray or urinalysis and cul-
ture should be considered if symp-
toms suggest infection, keeping in
mind that elderly patients can fail
to manifest typical signs of infec-
tion (elevated white blood cell count,
fever, or focal symptoms). Neuro-
Table 1. Nonpharmacological strategies for addressing delirium risk factors, based on the
Hospital Elder Life Program (HELP).14,16
Risk factors Strategies
Cognitive impairment Reorient patient, encourage cognitively stimulating activities
Sleep deprivation Reduce sleep interruptions with scheduling of care, promote
relaxation (e.g., offer warm milk, music), institute unit-wide noise
reduction
Immobility Ensure early mobilization, encourage range-of-motion exercise,
provide appropriate gait aids, minimize use of restraints
Vision impairment Provide visual aids
Hearing impairment Provide hearing amplification devices, use adaptive communication
techniques
Dehydration Recognize and treat dehydration, offer feeding assistance
Other Reposition patient to prevent aspiration, review medications,
discontinue catheter use if possible
imaging is indicated for patients recurrence rates,14 suggesting that
with focal neurological deficits, un- once delirium develops, it is difficult
explained confusion, or suspected to intervene.
head trauma.1 Worsening severity or A recent meta-analysis has shown
a prolonged course should prompt a that nonpharmacological interven-
repeat workup for ongoing medical tions not only reduce the incidence
instability, new precipitants, or less of delirium but also prevent falls.15
common causes of delirium such as Other important strategies include
encephalitis, rapidly progressive de- managing pain, maintaining nutri-
mentia, or seizure.1 Neuroimaging, tion, and performing a thorough med-
lumbar puncture, and electroencepha- ication review.16 Discontinuation of
logram should be considered in these urinary catheters whenever possible
situations. is encouraged given the association
of catheters with urinary tract infec-
Nonpharmacological tions. Involving the patients family,
strategies for prevention primary bedside nurse, and clinical
Primary prevention is the corner- nurse leader in the creation of a nurs-
stone of delirium management and ing care plan can also be instrumental
has the best evidence for success of in the success of these nonpharma-
any intervention. Some institutions cological delirium prevention strate-
have adopted the Hospital Elder Life gies. Other important aspects of the
Program (HELP) to address six risk care plan include assisted feeding and
factors in older patients that com- positioning in bed to prevent aspira-
monly contribute to delirium: cogni- tion, frequent turning to prevent skin
tive impairment, sleep deprivation, breakdown, and minimizing the use
immobility, visual impairment, hear- of restraints given the association of
ing impairment, and dehydration restraints with injury and worsened
( Table 1 ).14 Addressing these risk fac- delirium.17 If restraints must be used,
tors results in fewer days of delirium the patient should be supervised vigi-
and fewer episodes of delirium, but lantly and the restraints discontinued
does not reduce delirium severity and as soon as possible.
bc medical journal vol. 59 no. 3, april 2017 bcmj.org 167
 Delirium in older adults: Diagnosis, prevention, and treatment

Given the complex nature of car- Typical and atypical antipsychot- toms of delirium is considered off-
ing for older adults, a comprehensive ics may be considered for manage- label. Risks and benefits of treatment
geriatric assessment (CGA) by a geri- ment of delirium even though there should be discussed before initiating
atrician or a physician with exper- is inconclusive evidence that antipsy- antipsychotic therapy, and families
tise in geriatric care can help identify chotic use reduces delirium severity should be involved to see if alternative
treatment goals and coordinate care. or duration.20 Studies of antipsychot- nonpharmacological strategies can be
A number of studies in the orthotrau- ics in delirium have largely been used instead. Treatment should be for
ma population have shown that a pro- small and of varying quality. The a short time, and down-titration or
active perioperative CGA can reduce types and doses of antipsychotics, as discontinuation should be considered
the incidence of delirium.18,19 well as the populations studied, have on a daily basis. Typically, we start
been heterogeneous, making it diffi- geriatric patients on lower doses and
Treatment cult to generalize from the findings. titrate as appropriate ( Table 2 ). Con-
Sometimes a patients behaviors con- Potential side effects include extra sultation with geriatric medicine, care
tinue to be concerning despite man- pyramidal symptoms (EPS), includ- of the elderly services, or a geriatric
agement of the underlying cause of ing parkinsonism, akathisia, and psychiatry physician, if available, can
the delirium. Treatment with medica- dystonia, and prolongation of the QTc help guide management when medi-
tion can be an option if nonpharmaco- interval, particularly with use of hal- cations are being considered.
logical strategies such as one-on-one operidol and quetiapine.21 While the Recent studies suggest that anti
reorientation from a family member atypical antipsychotics are generally psychotics are useful in delirium
or trained care aide cannot prevent believed to have a lower propensity to prophylaxis, particularly in the post-
aggression or severe agitation and induce EPS, prolonged use in patients surgical period. However, there is a
patient or staff safety is threatened. with dementia has been associated large variation in the surgical patient
Medication is also an option if there is with increased mortality.22 population studied as well as in the
sleep-wake disturbance or psychosis. Despite these drawbacks, anti- regimens used. A recent meta-analysis
However, it is important to remember psychotics can be used in limited showed that perioperative olanzapine
that not all behaviors need to be con- circumstances with the understand- and risperidone were useful in delir-
trolled by medication, nor do medica- ing that the potential for side effects ium prevention, while no difference
tions address the underlying cause of and the lack of robust evidence means was found when haloperidol was com-
the behavior. that use of antipsychotics for symp- pared with a placebo.24 Because of the
heterogeneity of results and small ef-
Table 2. Medications for management of delirium symptoms in older adults. fect size, the off-label use of prophy-
lactic antipsychotics perioperatively
Medication Dose (every 68 hours)* has not become standard of care.
Typical antipsychotics Similarly, there have been sev-
(oral, intramuscular, and subcutaneous forms; all use is off-label) eral studies looking at the effects of
melatonin on the prevention of de-
Loxapine 2.505.00 mg
lirium. Al-Aama and colleagues stud-
Methotrimeprazine 2.505.00 mg ied 145 elderly medical patients in a
Haloperidol 0.250.50 mg
randomized double-blinded placebo-
controlled trial and found that the mel-
Atypical antipsychotics atonin group had a significantly lower
(oral form; all use is off-label)
risk of delirium incidence,25 while de
Quetiapine 6.2512.50 mg Jonghe and colleagues studied the
Risperidone 0.250.50 mg effect of melatonin on the incidence
of delirium in older patients with hip
Olanzapine (also available in intramuscular form) 1.252.50 mg
fracture but did not find melatonin ef-
* Usual starting dose is at the lower end of the range. Robust individuals may require higher doses ficacious.26 Overall, there is weak evi-
than listed. An additional regular afternoon and/or evening dose may be considered for patients dence that melatonin is effective for
who predictably exhibit an escalation of symptoms later in the day.
the prevention of delirium. However,

Maximal dose of haloperidol is 4.50 mg per day, beyond which extrapyramidal symptoms can be
significant.23 melatonin has a good safety profile

168 bc medical journal vol. 59 no. 3, april 2017 bcmj.org

 Delirium in older adults: Diagnosis, prevention, and treatment
and may be a reasonable choice to
start in hospitalized patients at high
risk for delirium, or in established de-
lirium as a sleep aid. Doses between
0.5 and 9.0 mg have been studied in
delirium and in dementia patients,
with 3.0 to 6.0 mg being used com-
monly in clinical practice.27
Given the cholinergic deficit
theory in the pathogenesis of deliri-
um, there have also been trials with
acetylcholinesterase inhibitors, medi-
cations that increase the amount of
acetylcholine in the synapse. Don
epezil and rivastigmine have been
studied in randomized controlled tri-
als for both the prevention and the
treatment of delirium, but the results
have been disappointing. One of the
largest studies of rivastigmine as an
adjunct to usual care with haloperi-
dol in intensive care unit patients was
stopped early after higher mortality in
the rivastigmine group was observed,
even though the difference was not
statistically significant.28 Similarly,
studies show that donepezil is not ef-
fective for delirium prophylaxis and
treatment.29,30
Summary
Delirium during hospitalization indi-
cates medical instability that can affect
a patients independence after dis-
charge. While the exact pathophysi-
ology of delirium is not completely
understood, certain well-established
in-hospital risk factors can be iden-
tified and addressed. These include
cognitive impairment, sleep depriva-
tion, immobility, visual impairment,
hearing impairment, and dehydration.
Ideally, nonpharmalogical strategies
should be used to address these risk
factors. The most effective approach
is prevention, followed by treatment
of the underlying cause. Drug ther-
apies can be used if the safety of the
patient and staff is a concern, but cau-
tion is advised given the side effects
associated with certain medications. factors for delirium in hospitalized elderly
Typical and atypical antipsychotics persons. Predictive model and interrela-
may be used on an off-label basis for tionship with baseline vulnerability. JAMA
a short time and if down-titration and 1996;275:852-857.
discontinuation are considered on a 5. van Gool WA, van de Beek D, Eikelen-
daily basis. boom P. Systemic infection and delirium:
In some institutions, efforts have When cytokines and acetylcholine collide.
been made to systematically imple- Lancet 2010;375(9716):773-775.
Typical and atypical antipsychotics
may be used on an off-label basis
for a short time and if down-
titration and discontinuation are
considered on a daily basis.
ment measures to prevent and treat 6. Hshieh TT, Fong TG, Marcantonio ER, In-
delirium. When delirium does occur, ouye SK. Cholinergic deficiency hypothe-
the medical team and family should sis in delirium: A synthesis of current evi-
be aware that the patient may need dence. J Gerontol A Biol Sci Med Sci
further support on discharge given 2008;63:764-772.
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decline associated with delirium. Engl J Med 2006;354:1157-1165.
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Competing interests interface between delirium and dementia
None declared. in elderly adults. Lancet Neurol 2015;14:
823-832.
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