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Delirium: a Challenge in Prevention
Summer School of Neuroscience and Aging
Venice, Italy 10-14 June, 2013
Richard W. Besdine, MD,FACP
Professor of Medicine
Greer Professor of Geriatric Medicine
Director, Division of Geriatrics and Palliative Medicine
Director, Center for Gerontology and Health Care Research
ALPERT
MEDICAL
SCHOOL
OBJECTIVES
Know and understand:
 What is delirium?
 How to recognize and diagnose delirium
 Predisposing and precipitating risk factors
 How to evaluate and treat elders with
delirium
 Interventions to prevent and treat delirium
Other Names for Delirium (AKA)



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
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Acute confusional state
Acute mental status change
Altered mental status
Organic brain syndrome
Reversible dementia
Toxic or metabolic encephalopathy
Morbidity/Consequences of Delirium
A 10-fold risk of death in hospital
 A 3-5 fold  risk of nosocomial complications, postacute NH placement
 ↑ Length of stay, morbidity, mortality, costs
 Poor functional recovery, mortality for 2 years
 Acceleration of decline of dementia symptoms
 Persistence of delirium, poor long-term outcomes
 Decreased physical function
 Institutionalization, prolonged rehabilitation

Epidemiology, Detection of Delirium

1/3 of older patients presenting to the ED

1/3 of inpatients aged 70+ on general medical
units, half of whom are delirious on admission

Under-recognition - nurses recognize, document
< 50%; MDs recognize, document only 20%

DSM-IV criteria precise, difficult to apply

Confusion Assessment Method (CAM) performs
better clinically: >95% sensitivity, specificity
Detecting Delirium
Recognized
by MDs
Not recognized


Recognized
by nurses
Not recognized
Nurses recognize, document <50% of cases
Physicians recognize, document only 20%
DSM-IV Diagnostic Criteria

Disturbance of consciousness, reduced ability to
focus, sustain, or shift attention

Change in cognition (e.g., memory, disorientation,
language disturbance) or a perceptual disturbance
not better accounted for by existing dementia

Develops quickly (hours to days) and fluctuates

Evidence from history, physical or labs of direct
physiologic consequence of a medical condition
Confusion Assessment Method
Requires features 1 and 2, and either 3 or 4:
1. Acute change in mental status and fluctuating
clinical course
2. Inattention by testing
3. Disorganized thinking
4. Altered level of consciousness
Varieties of Delirium



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Hyperactive or agitated delirium - 25% of all
cases
Hypoactive delirium - less recognized or
appropriately treated
Mixed
Additional features include emotional
symptoms, psychotic symptoms,
“sundowning”
Neuropathophysiology: Cholinergic
Deficiency Hypothesis

Acetylcholine is an important neurotransmitter for
cognition

Delirium can be caused by anti-cholinergic drug
overdose, and can be reversed by physostigmine

Delirium is associated with  serum anticholinergic activity

Anti-cholinergic activity is found in delirious
patients taking no anti-cholinergic drugs
Neuropathophysiology: Inflammation

Especially important in postoperative, cancer and
infected patients

Delirium associated with ↑ C-reactive protein, ↑
interleukin-1β, and ↑ tumor necrosis factor

Inflammation can break down blood-brain barrier,
allowing toxic medications and cytokines access
to CNS
Delirium as a Geriatrics Syndrome

Delirium, as with falls, is a result of the
cumulative sum of predisposing (already
present) and precipitating (new) factors

The more predisposing factors present, the
fewer precipitating factors required to cause
delirium, and vice versa

The more risk factors present, the more likely it
is that delirium will occur

Intervening to modify or eliminate risk factors
will reduce the likelihood of delirium
Relationship Between Predisposing and
Precipitating Risk Factors
Risk Factors for Delirium
Predisposing
Precipitating
Dementia
Co-morbidity
Sensory loss
Advanced Age
Functional loss
Malnutrition
Male, alcohol
Psychoactive Meds
Restraints, Catheter, Bed rest
Acute Illness
Fecal impaction, Retention
Surgery, Anesthesia
Pain
Sleep Deprivation
Sensory Deprivation
Fluid/electrolyte disorder
Identification of Risk Factors
Initial Evaluation:
 History, physical exam, vital signs
 Targeted lab tests, search for infections
Review medications:
 Prescription, PRN, OTC, herbal
 Lower, stop or change any dangerous drugs
Further options:
 Laboratory tests: thyroid, B12, drug levels,
toxicology screen, ammonia, cortisol, ABG
 Brain imaging, LP, EEG
Address all risks identified
One-Year Mortality of Delirium

919 patients enrolled in a delirium
prevention intervention in 1995

100% follow-up one year following
hospitalization with telephone interviews
and review of death certificates

Those with delirium had ~50 days (0.13
of a year) of life lost, controlling for clinical
covariates (p<0.001)
Leslie DL, Arch Int Med 2005;165:1657
Survival Estimate
Fitted Survival Curves With and Without Delirium
919 Discharged patients, 1year follow up;
delirious patients averaged 50 fewer days of life
Leslie DL, Arch Int Med 2005;165:1657
Discharge
Survival Probability
___
ED Not delirious
_ _ _ Delirious
Days
105 ED patients discharged, 30 with delirium. After adjusting for age, sex,
function, cognition, co-morbid conditions and # meds, delirious patients were 7
times more likely to be dead at 6 months
Kakuma R et al.. JAGS 2003;51:443
Delirium Prevention Targets (High Risk)
Baseline cognitive impairment – orientation,
avoid drugs, therapeutic activities
 Sleep – non-pharmacologic intervention,
environmental changes
 Immobility – PT, maximum mobilization
 Vision – aids (glasses, magnifiers), equipment
(large print, touch pads)
 Hearing – amplification, ear wax removal
 Dehydration - early recognition, volume repletion

Inouye S, et al. NEJM 1999;340:669-676
Delirium Prevention

Aim: reduce rate of incident delirium using a targeted
multiple component intervention in high risk patients

Intervention: nurse/volunteer-based protocols for
addressing identified risk factors in 852 medical inpatients aged >65, 1995-98

Incident delirium reduced from 15% in control group
to 9.9% in intervention group (34% risk reduction, P=0.02)

Hospital days reduced by one-third (P=0.02)

But delirium that did occur in intervention group was
not attenuated
Inouye S, et al. NEJM 1999;340:669-676
Intervention to Reduce Delirium
Inouye S, et al. NEJM 1999;340:669-676
Management – No Drugs

Adequate stimulation – hearing, vision

Mobility – avoid bed rest, mobilize ASAP,
avoid restraints (including catheters)

Vision and hearing

Nutrition – dentures, feeding help

Orientation - day, time, place, people, tests

Sleep hygiene
No-Drug Sleep Protocol

Warm drink, relaxing music, quiet dark room, back
rub, minimize awakenings

Quality of sleep correlated with the # of parts of the
protocol received

Decreased sedative use from 54% to 31%

Sleep protocol had a higher association with quality
of sleep than a sedative

Not as effective in chronic users of sedatives
McDowell et al. JAGS 1998;46:700
Guideline for Delirium Prevention
Assessment and modification of key clinical factors
that may precipitate delirium, including
Cognitive impairment
 Dehydration
 Constipation
 Hypoxia
 Infection
 Immobility
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Limited mobility
Multiple medications
Pain
Poor nutrition
Sensory impairment
Sleep disturbance
O'Mahony R et al. Ann Intern Med. 2011;154:746-51
Management - Drugs

Drugs increase severity and duration of delirium

All neuroleptics produce extrapyramidal disorders,
over-sedation, increased risk of stroke and death

Haloperidol only drug in randomized trials that was
better than others (or better than placebo) in
reducing dangerous behavior

If severe agitation is a danger to self or others, or
interferes with essential therapy, haloperidol, 0.251.0mg IV/PO every 30 minutes until sedated (max
3-5mg/24 hours), then ½ loading dose each 24
hours in divided doses – taper in DAYS
Pharmacologic Treatment of Delirium
Inouye S. N Engl J Med 2006;354:1157-1165
Post-Operative Delirium1
50%
50%
Cardiac surgery,
AAA repair
surgery
Hip fracture
repair
15%
Elective
noncardiac
surgery
Post-Operative Delirium2

Pre-operative risk factors:

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Age 70 and older
Cognitive impairment
Physical functional impairment
History of alcohol abuse
Abnormal serum chemistries
Intra-thoracic or aortic aneurysm surgery
50%
10%
2%
No pre-op 1 or 2 pre-op 3+ pre-op
risk factors risk factors risk factors
Summary
 Delirium
 High
is common, major morbidity for older persons
sensitivity and specificity for detection by CAM
 Careful
Hx, PE, focused labs will detect cause
 Careful
medication review mandatory; D/C possible
contributory agents
 Managing
delirium requires Rx of primary disease,
avoiding complications, managing behavioral
problems, providing rehabilitation
 The
best treatment for delirium is prevention
Case 11
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
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A 72-year-old man is evaluated because nurses
are concerned about his agitation, which
increases markedly in the evenings
He underwent emergency hip replacement 3 days
ago after he fell and fractured his hip
He gets antipsychotic agents to control agitation
at night; he yells “help me” constantly, and is
determined to get out of bed alone and walk
In the year before his fall, he had stopped
working and driving, but we don’t know why
Case 12

The patient’s history includes hypertension,
benign prostatic hyperplasia, and osteoarthritis;
there is no history of dementia

On examination, he appears confused and is
disoriented to place and time

He has some pain with hip movement

Neurologic examination reveals no focal
abnormalities
Case 13
Which of the following is most helpful in
establishing the diagnosis of delirium?
A. Order electrolytes, BUN, glucose, and
thyrotropin
B. Determine why the patient stopped working
and driving
C. Perform the digit-span memory test
D. Order CT of the brain
E. Review the patient’s medication list
DSM-IV Diagnostic Criteria

Disturbance of consciousness, reduced ability to
focus, sustain, or shift attention

Change in cognition (e.g., memory, disorientation,
language disturbance) or a perceptual disturbance
not better accounted for by existing dementia

Develops quickly (hours to days) and fluctuates

Evidence from history, physical or labs of direct
physiologic consequence of a medical condition
Confusion Assessment Method
Requires features 1 and 2, and either 3 or 4:
1. Acute change in mental status and fluctuating
clinical course
2. Inattention by testing
3. Disorganized thinking
4. Altered level of consciousness
Case 14
Which of the following is most helpful in
establishing the diagnosis of delirium?
A. Order electrolytes, BUN, glucose, and
thyrotropin
B. Determine why the patient stopped working
and driving
C. Perform the digit-span memory test
D. Order CT of the brain
E. Review the patient’s medication list
Case 21

An 89-year-old man is admitted to a nursing
home for rehabilitation after being hospitalized for
pneumonia; he is anxious and fidgety

He is widowed and lives in the community

History includes hypertension, benign prostatic
hyperplasia, major depressive disorder and
chronic back pain

Medications on transfer to the nursing home
include metoprolol, oxybutynin, paroxetine,
acetaminophen with codeine and amitriptyline
Case 22
Which of the following medications is least likely to
contribute to delirium?
A. Amitriptyline
B. Acetaminophen with codeine
C. Oxybutynin
D. Paroxetine
E. Metoprolol
Case 22
Which of the following medications is least likely to
contribute to delirium?
A. Amitriptyline
B. Acetaminophen with codeine
C. Oxybutynin
D. Paroxetine
E. Metoprolol
Case 31

A 90-year-old man is brought to the emergency
department by his family because he has had an
abrupt change in behavior

The patient moved into his daughter and son-in-law’s
house a few months ago, because he was no longer
able to manage living alone

A few days ago he became aggressive and angry,
and hit his son-in-law for no apparent reason

He has also become incontinent in the last 2 days
Case 32

He has multiple bruises, which the family suspects
are from falling

The patient’s history includes moderate dementia
and benign prostatic hyperplasia

Blood pressure is 160/90 mmHg; all other vital signs
are normal, and the physical exam is unremarkable

He is demanding to be released from “prison” and is
aggressive with the staff

He is uncooperative with the neurologic exam, but he
appears to be moving all extremities well
Case 33
What is the most appropriate next step?
A. Bladder scan
B. Lumbar puncture
C. Electroencephalography
D. CT of the brain
E. Basic metabolic panel, CBC, and pulse oximetry
Case 33
What is the most appropriate next step?
A. Bladder scan
B. Lumbar puncture
C. Electroencephalography
D. CT of the brain
E. Basic metabolic panel, CBC, and pulse oximetry