Transcript Delirium: Pathogenesis, Diagnosis and Treatment

Section of Physical Medicine and
Rehabilitation
presents
GRAND ROUND
5/13/2005
by
Anthony Tam Pham, DO
Case Report
 Ms. A, a 74-year old white woman who was
diagnosed w late-onset bipolar affective disorder
at the age of 69, came to the hospital after
sustaining a R hip fracture from fall. In the
emergency room, she was alert and fully oriented.
She received 4 mg of IV morphine sulfate for
pain. She slept well and answered questions
appropriately the next morning but was drowsy.
 After hip arthroplasty the following day, she was
awake but verbally unresponsive. The next day,
she continued to exhibit a blank expression,
lethargy, and minimal verbal responses.

Rehab was consulted for 9G placement for post-op
rehab.
 At the consultation, she displayed a fluctuating
level of consciousness, was disoriented to place
and time, had poor attention, uttered only a few
words and short phrases, but was pleasant. She did
not report feeling depressed, manic, or anxious.
Her score on the Mini Mental State Examination
was 10 out of 30. Her performance on the clockdrawing task was poor.

PMH: HTN, DM, bipolar disorder, CHF
no history of stroke, dementia
 PSH: just hip arthroplasty
 All: none
 Med: Lopressor, Glucotrol, lithium, ASA,
Lovenox, Percocet prn, dulcolax.
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Her psychiatrist recommended obtaining an EEG
and Head CT. Results showed diffuse slowing and
mild small vessel ischemic changes, respectively.
EEG findings supported the diagnosis of delirium,
and Ms A was given donepezil, 5 mg/day.
The next day, she was better but still confused and
sleepy.
The second day, she was alert and conversant, and
displayed some insight.
The following day, she was alert, fully oriented,
displayed good eye contact and normal
psychomotor activity. MMSE was 20/30.
She was then transferred to 9G for post-op rehab.
DELIRIUM:
pathogenesis, diagnosis, and
treatment
Definition and terminology
DSM –IV
1. Disturbance of consciousness with reduced
ability to focus, sustain, or shift attention.
2. not better accounted for by a preexisting,
established, or evolving dementia.
3. Over a short period of time (usually hours to
days), fluctuating during the course of the day
4. Evidence that it is caused by a medical
condition, substance intoxication, or medication
side effect.
Additional features


Psychomotor behavioral disturbances such
as hypoactivity, hyperactivity w increased
sympathetic activity, impairment in sleep
duration and architecture
Variable emotional disturbances, such as
fear, depression, euphoria, or perplexity.
Epidemiology of delirium

30% - older medical patients
 10-50% - older surgical patients
 70% - ICU
 42% - Hospice units
 16% - postacute care settings
 Delirium patients experience prolonged
hospitalizations, functional decline, high
risk for institutionalization.
Pathogenesis of delirium

Poorly understood
 Difficult to study severely ill patients
 Hard to separate from that of underlying
illness and drug treatment
Pathogenesis: 1.Neurobiology
of attention
Arousal and attention are governed by:
 the ascending reticular activating system
 The “nondominant” parietal and frontal
lobes
 Intact higher order integrated cortical
function
Pathogenesis:
2. Neurotransmitter
1. Acetylcholine
 Cause delirium when given to healthy
person
 More likely to lead to confusion in frailty
elderly
 Effects reversed with cholinesterase
inhibitors (physostigmine).

Medical conditions precipitating delirium,
such as hypoxia, hypoglycemia, thiamine
deficiency, decrease acetylcholine synthesis
in CNS
 Alzheimer’s disease, characterized by a loss
of cholinergic neurons, increases risk of
delirium due to anticholinergic medications.
neurotransmitters
2. Alterations in neuropeptides (eg,
somatostatin), endorphins, serotonin,
norepinephrine, and GABA
3. Cytokines, such as interleukins and
interferons
Pathogenesis: (3)
risk factors

Multifactorial
 Underlying brain diseases, such as
dementia, stroke, Parkinson’s disease
 Advanced age and sensory impairment
Pathogenesis: (4)
precipitating factors

Polypharmacy (particularly psychoactive
drugs)
 Infections
 Dehydration
 Immobility (including restraint use)
 Malnutrition
 The use of bladder catheters
Clinical presentation of
delirium
1. Disturbance of consciousness
 A change in the level of awareness and the
ability to focus, sustain, or shift attention.
–
–


Often subtle, may precede by one day or
more.
Patient “isn’t acting quite right”
Distractibility, often evident in
conversation.
Appearing drowsy, lethargic, or even
semi-comatose in advanced cases.
2. Change in cognition
 Cognitive problems: memory loss,
disorientation, difficulty with language and
speech.
– Need to ascertain baseline.

Perceptual problems: misidentify the
clinician, vague delusions of harm.
– Visual and tactile hallucinations are uncommon
3. Temporal course
 Develop over hours to days and typically
persist for days to months
 Acuteness of presentation is the most
helpful feature in differentiating from
dementia.
 Fluctuating: typically most severe in the
evening and at night, and relatively lucid
during morning.
4. Other features
 Not essential diagnostic but common,
including psychomotor agitation, sleepwake reversals, irritability, anxiety,
emotional lability, and hypersensitivity to
lights and sounds.
 Common among older patients includes
relatively quiet, withdrawn state that
frequently is mistaken for depression.
Evaluation of delirium (1)

Two important aspects to the diagnostic
evaluation: recognizing that the disorder is
present, and uncovering the underlying
cause.
 In some reports, clinicians fail to recognize
delirium in 70 percent of cases.
 Wrongly attributed to the patient’s age, to
dementia, or to other mental disorders such
as depression.
Must not “normalize” lethargy or
somnolence by assuming that illness, sleep
loss, fatigue, or anxiety cause the change.
 Require knowledge of the patient’s baseline
level of functioning.

Evaluation (2):
Confusion
Assessment
Method
(CAM):
- sensitivity of 94
to 100 percent;
- specificity of 90
to 95 percent
- a standard
screening device
in clinical studies
of delirium
Evaluation (3)

Investigating medical etiologies:
– Fluid and electrolyte disturbances (dehydration,
hyponatremia and hypernatremia)
– Infections (urinary, respiratory, skin and soft
tissue)
– Drug or alcohol toxicity
– Withdrawal from alcohol
– Withdrawal from barbiturates, benzodiazepines,
and SSRI
– Metabolic disorders (hypoglycemia,
hypercalcemia, uremia, liver failure,
thyrotoxicosis)
– Low perfusion states (shock, heart failure)
– Postoperative states, especially in the elderly
Evaluation
(4):
medication
review
Differential Diagnosis
1.
2.
Sundowning: a frequently seen but poorly
understood; seen in evening hours;
typically in demented, institutionalized
patients.
Focal syndromes
 Temporal-parietal: patients w Wernicke’s
aphasia – not comprehend, obey, seem
confused; but restricted to language.
– Occipital: Anton’s syndrome of cortical
blindness and confabulation
– Frontal: bifrontal lesions (eg, from tumor or
trauma) often show akinetic mutism, lack of
spontaneity, lack of judgment, problems w
recent or working memory, blunted or labile
emotional responses.
3. Nonconvulsive Status Epilepticus (NCSE):
– Requires EEG for detection
– Show no classical ictal features
– Features: prominent bilateral facial twitching,
unexplained nystagmoid eye movements during
obtunded periods, spontaneous hippus,
prolonged “ post-ictal state”, automatisms (lip
smacking, chewing, swallowing movements).
4. Dementia
– Alzheimer’s – cognitive change is insidious,
progressive, without much fluctuation, over a
much longer time (months to years).
– Lewy bodies – similar to Alzheimer’s, but
fluctuations and visual hallucinations are more
common and prominent.
5. Primary psychiatric illnesses:
– Depression (poor sleep, difficulty w attention or
concentration)
– Mania
Laboratory testing

Serum electrolytes, creatinine, glucose, calcium,
CBC, and urinalysis
 Drug levels, when appropriate.
– Delirium can occur even w “therapeutic” levels
(digoxin, lithium, or quinidine)

Toxic screen of blood and urine
 Blood gas: Respiratory alkalosis is due to early
sepsis, hepatic failure, early salicylate
intoxication. Metabolic acidosis reflects uremia,
diabetic ketoacidosis, lactic acidosis, late phases
of sepsis or salicylate intoxication, methanol,
ethylene glycol
Neuroimaging

Head CT may be used selectively rather
than routinely for evaluating delirium.
 May not be necessary if:
– An obvious treatable medical illness or problem
– No evidence of trauma
– No new focal neurologic signs are present
– Patient is arousable and able to follow simple
commands.

Head CT may be required if:
– Delirium does not improve despite appropriate
treatment of underlying medical condition
– The neurologic examination is confounded by
diminished patient responsiveness or
cooperation.
Lumbar puncture

CSF analysis is the only diagnostic tool for
the following mostly treatable conditions in
delirium patients:
– Bacterial meningitis
– Encephalitis
– Nonbacterial CSF pleocytosis (eg, aseptic
meningitis, carcinomatous meningitis,
encephalitis, seizures)
– Elevated CSF glutamine concentration in
hepatic encephalopathy
– Elevated opening pressure due to increased ICP

LP is mandatory when the cause of delirium
is not obvious.
EEG

Should be obtained for any patient with
altered consciousness of unknown etiology.
 Useful to:
– Exclude seizures, esp. nonconvulsive or
subclinical seizures
– Confirm the diagnosis of certain metabolic
encephalopathies or infectious
encephalopatides

Nonconvulsive seizures lack motor
manifestations or convulsions, but may
impair consciousness.
 Nonconvulsive status epilepticus may
cause continuous or fluctuating impairment
of consciousness.
 Metabolic encephalopathies may show
diffuse bilateral slowing of background
rhythm and high wave amplitude.
 Viral encephalitis may show diffuse
background slowing and occasional
epileptiform activity.
Treatment
1.
Multicomponent intervention


Standardized protocols to control six risk factors for
delirium: cognitive impairment; sleep deprivation;
immobility; visual impairment; hearing impairment;
and dehydration.
Of 852 hospitalized pts aged 70 or older; resulted in
significant reduction in the number of delirium
episodes vs usual care ( 62 vs. 90) and in the total
number of days w delirium (105 vs 161)
Inouye, Bogardus, Charpentier. A Multicomponent intervention to
prevent delirium. NEJM 1999.
Managing disruptive behaviors

Physical restraints should be used only as a last
resort since they frequently increase agitation and
create additional morbidity.
 Hospital environment, characterized by high
ambient noise, poor lighting, lack of windows,
frequent room changes, and restraint use, often
contribute to worsening confusion.
 Frequent reassurance, touch, and verbal
orientation from familiar persons lessen disruptive
behaviors.
Psychotropic medication

A review by the Cochrane Collaborative found
only one high-quality randomized trial, which
compared haloperidol, chlorpromazine, and
lorazepam in the treatment of delirium
 Recommendation: low-dose haloperidol (0.5 to
1.0 mg PO, IV, or IM) be used to control agitation
or psychotic symptoms.
Jackson, Lipman. Drug therapy for delirium in terminally ill patients. The
Cochrane Library, issue 2, 2004.

Older patients are more likely to experience severe
extrapyramidal effects w haloperidol (akathisia,
potential fatal neuroleptic malignant syndrome)
 The newer antipsychotic agents (risperidone,
olanzapine) have fewer extrapyramidal side
effects.
 Benzodiazepine (lorazepam 0.5 to 1.0 mg) have a
more rapid onset of action (5 min after parenteral),
but they commonly worsen confusion and
sedation. Drug of choice only in cases of sedative
drug and alcohol withdrawal.
Summary
:
Delirium
workup
scheme
Summary
:
Common
causes of
Delirium
Summary:
common
culprit
drugs