Delirium

CHAIR PERSON : DR SAFEEKH AT

PRESENTER : DR CHANDINI

Introduction

Delirium is characterized by an acute decline in both the

level of consciousness and cognition with particular

impairment in attention.

A life threatening, yet potentially reversible disorder of the

central nervous system (CNS)

Delirium often involves perceptual disturbances, abnormal

psychomotor activity and sleep cycle impairment

INTRODUCTION
3

DEFINED: Acute onset of fluctuating cognitive impairment &

disturbance of consciousness with reduced attention.
They are frequently associated with perceptual
abnormalities, sleep wake cycle disturbances, disorganized
thought process and abnormal psychomotor activity.

The term delirium originates from the Latin word

deliroto be crazy, which is taken from de + lira, a

furrow (i.e., To go out of the furrow)
Or Greek meaning off the track

History

The earliest known references to delirium in medical

literature are found in the writings of Hippocrates

2,400 years ago, in his Book of Epidemics.
Hippocrates described case of Erasinus - who lived

near the Canal of Bootes, who was seized with fever

after supper; passed the night in an agitated state.

History
The word delirium was first used by Celsus in the first

century AD.
Celsus - Used the term delirium to describe a spectrum

of mental disorders ranging from general insanity to

acute transient states of mental disturbance including
phrenitis, lethargus, hysteria, melancholia and mania.

History
Aretaeus of Cappadocia - was the first to classify mental

disorders into acute and chronic categories.

Aretaeus identified both phrenitis and lethargus as acute

manifestations of disease.
He introduced the concept that delirium is an acute syndrome

and that it consist of possible variants.

This distinction by Aretaeus may represent the first recorded

description of both the hyperactive and hypoactive motor

elements of delirium.

History
Phillip Barrough - described the concept of delirium in

his textbook- The Method of Physick.

Barrough proposed that delirium constituted a

derangement of some combination of three main internal

senses, including imagination, cognition and memory.
This concept of deranged senses was elaborated by

Thomas Willis in his treatise De Anima Brutorum.

Willis established that delirium was in fact a specific set

of symptoms and not a disease.

History
In 18th century, Erasmus Darwin and John Hunter

made significant contributions to the theory of delirium.

Darwin was the first to compare delirium with the dream

state, noting that both states constituted an interruption of

voluntary power and a suspension of the ability to attend
to one's external environment.
Darwin's notion was expanded by John Hunter, who

defined delirium as a cessation of consciousness of one's

own existence.

History
James Sims argued that delirium was distinctly different

from general insanity and that it constituted an alienation

of the mind.
Sims further distinguished two species of delirium, which

he referred to as low or raving, which correspond almost

perfectly with the modern concept of hypoactive and
hyperactive motor subtypes of delirium.
The 19th century saw critical advances in the development

of the concept of delirium.

Epidemiology
PREVALENCE of delirium at hospital admission
ranges from 14 to 24 percent
INCIDENCE of delirium arising during
hospitalization ranges from 6 to 56 percent.

Epidemiology
Delirium is a common disorder in elderly patients.
In community studies 1 percent of the elderly population aged

55 or more have delirium & 13 percent in the 85 and older.

At the time of admission to medical wards, between 15 and 20

percent of older patients meet criteria for delirium-prevalent

cases.
Delirium has been reported in 10 to 15 percent of general

surgical patients
30 percent of open heart surgery patients
over 50 percent of patients treated for hip fractures.
Delirium occurs in 70 to 87 percent of those in intensive care

units and in up to 83 percent of all patients at the end of life

care.

EPIDEMIOLOGY
INCIDENCE AND PREVALENCE
13

POPULATION

PREVALENCE RANGE % INCIDENCE RANGE %

GEN MED IP

10-30

3-16

MED & SUR IP

5-15

10-55

GEN SURG PTS

N/A

9-15 POST OP

CCU PTs

16

16-83

CARDIAC SURG

16-34

7-34

ORTHO SURG PTS

33

18-50

EMERGENCY DEPT

7-10

N/A

TERMINALLY ILL
CANCER PTS

23-28

83

INSTITUTIONALIZD
ELDERLY

44

33

Other Terms Describing Delirium

Acute confusional state

Acute brain failure
Encephalitis
Encephalopathy
Intensive care unit psychosis
Toxic metabolic state
Central nervous system toxicity
Paraneoplastic limbic encephalitis
Sundowning
Cerebral insufficiency
Organic brain syndrome

Risk factors
Predisposing Factors for Delirium
Functional Status
Functional dependence
Immobility
History of falls
Low level of activity
Sensory Impairment
Hearing
Visual

Risk factors
Predisposing Factors for Delirium
Demographic characteristics
Age 65 and older
Male sex
Cognitive status
Dementia
Cognitive impairment
History of delirium
Depression

Risk factors
Predisposing Factors for Delirium
Decreased Oral Intake
Dehydration
Malnutrition
Drugs
Treatment with psychoactive drugs
Treatment with drugs with anti cholinergic
properties
Alcohol abuse

Risk factors
Predisposing Factors for Delirium
Coexisting Medical Conditions
Severe medical diseases
Chronic renal or hepatic disease
Stroke
Neurological disease
Metabolic derangements
Infection with human immunodeficiency virus
Fractures or trauma
Terminal diseases

RISK FACTORS
Precipitating Factors for Delirium
Drugs
Sedative hypnotics
Narcotics
Anticholinergic drugs
Treatment with multiple drugs
Alcohol or drug withdrawal
Primary Neurologic Diseases
Stroke, nondominant hemispheric
Intracranial bleeding
Meningitis or encephalitis

RISK FACTORS
Precipitating Factors for Delirium
Intercurrent Illnesses
Infections
Iatrogenic complications
Severe acute illness
Hypoxia
Shock
Anaemia
Fever or hypothermia
Dehydration
Poor nutritional status
Low serum albumin levels
Metabolic derangements

RISK FACTORS
Precipitating Factors for Delirium
Surgery
Orthopaedic surgery
Cardiac surgery
Prolonged cardiopulmonary bypass
Non cardiac surgery

RISK FACTORS
Precipitating Factors for Delirium
Environmental
Admission to intensive care unit
Use of physical restraints
Use of bladder catheter
Use of multiple procedures
Pain
Emotional stress
Prolonged sleep depravation

PROTECTIVE FACTORS
23

1.Good premorbid functioning

2.Education programes that target clinicians,improving
coordination between consultants and primary care
givers
3.Focus on nutrition
4.Attention to visual and hearing impairment
5.Increased rehabilitation

Etiology

ETIOLOGY
Development of delirium is multifactorial, including

stress or trauma to the CNS, drug toxicity or

withdrawal, and metabolic disorders arising from
organ failure.
Despite the numerous etiologies that have been noted,

yet to elucidate the underlying pathophysiology of

delirium.
Current research indicates that mechanisms such as
neurochemical abnormalities, inflammatory changes,
oxidative stress and bloodbrain barrier dysfunction
may all contribute to the pathogenesis of delirium.

Etiology
General disruption in higher cortical function with

dysfunction in the prefrontal cortex, subcortical structures,

thalamus, basal ganglia, frontal and temporoparietal
cortex, fusiform cortex and lingual gyri
Cholinergic deficiency
Dopaminergic excess
Glutamate excitotoxicity
Increased serum GABA levels and ammonia
Cytokines increase permeability of BBB and alter

neurotransmitters

SITE
1) Primary neuroanatomical site involved
is the RETICULAR FORMATION
2) Generalized disruption in higher cortical function,
with dysfunction in the prefrontal cortex,
subcortical structures, thalamus, basal ganglia,
frontal and temporoparietal cortex, fusiform
cortex, and lingual gyri, particularly on the
nondominant side.

PATHWAY
The major pathway involved in delirium is the dorsal
tegmental pathway projecting from the
mesencephalic reticular formation to the tectum and
the thalamus

Neurochemical
Patients with delirium have shown evidence of
neurochemical changes in
Acetylcholine
Dopamine
Glutamate
-aminobutyric acid (GABA)
Serotonin systems.

Neurochemical

Acetylcholine
The role of cholinergic deficiency in delirium - is involved in rapid eye

movement (REM) sleep, attention, arousal, and memory.

Administration of anticholinergic drugs can induce delirium in humans

and animals and serum anticholinergic activity is increased in patients

with delirium.
Physostigmine , a cholinergic agent, reverses delirium associated with

anticholinergic drugs.
Physostigmine has also demonstrated benefit in nonanticholinergic

delirium such as delirium from alcohol withdrawal, ketamine anesthesia,

H2 receptor antagonist delirium, and -hydroxybutyric acid withdrawal.
This suggests the possibility of interactions between other systems and

the cholinergic system in the pathophysiology of delirium.

Neurochemical

Dopamine
Dopaminergic excess also appears to contribute to delirium,

possibly owing to its regulatory influence on the release of

acetylcholine.
One suggested mechanism is the involvement of dopamine in

maintaining and shifting attention.

Dopaminergic drugs - levodopa and bupropion are

recognized precipitants of delirium and dopamine antagonists

( antipsychotic agents) effectively treat delirium symptoms.

Neurochemical

Glutamate
Glutamate through its excitatory neurotoxicity effects

(mediated via the N-methyl-D-aspartate [NMDA] receptor)

may cause neuronal death and can be associated with
delirium.
Drugs that are NMDA antagonists such as ketamine and

phencyclidine (PCP) are associated with delirium.

One proposed mechanism of Wernicke's encephalopathy is

through glutamate abnormalities

Neurochemical

GABA
GABA, an inhibitor of brain activity has been implicated in
contributing to delirium secondary to benzodiazepine and
alcohol withdrawal.
Hepatic encephalopathy has been associated with increased
serum ammonia and GABA levels.
Serotonin
Perturbations of other neurotransmitters such as

norepinephrine, serotonin, GABA, glutamate, and melatonin,

may also have a role in the pathophysiology of delirium, but the
evidence is less well developed.
These neurotransmitters may exert their influence through
interactions with the cholinergic and dopaminergic pathways.

Neurochemical

Oxidative Metabolism
Disturbance in brain oxygen supply versus demand has

been one of the theories proposed for delirium.

Impaired oxidative metabolism appears to be a

predisposing factor for later development of delirium.

Neurochemical

BloodBrain Barrier Alterations

One hypothesis of delirium is that it is a CNS response to systemic

inflammation during a state of bloodbrain barrier compromise.

In postcardiac surgery patients, chemokines, which is an inflammatory

marker have been associated with delirium by disrupting the blood

brain barrier.
Similar alterations have been found in patients developing delirium

after trauma, primary hyperparathyroidism and delirium tremens.

Neurochemical

Ammonia
Ammonia and several other factors are known to

induce and aggravate astrocyte swelling, which

initiate a cascade of events leading to delirium.
Another mechanism could be that elevated ammonia

levels can contribute to increased glutamate and

glutamine levels, which are precursors to GABA.

Neurochemical

Cytokines including interleukin-1, interleukin-2,

interleukin-6, tumor necrosis factor- (TNF-), and

interferon may contribute to delirium by increasing the
permeability of the bloodbrain barrier and altering
neurotransmission.
Chronic stress brought on by illness or trauma activates the
sympathetic nervous system and hypothalamicpituitary
adrenocortical axis resulting in increased cytokine levels
and chronic hypercortisolism.
Chronic hypercortisolism has deleterious effects on
hippocampal serotonin (5-hydroxytryptamine) 5-HT1A
receptors which may contribute to delirium.

ICD 10
For a definite diagnosis, symptoms, mild or severe, should be
present in each one of the following areas:
(a) Impairment of consciousness and attention (on a
continuum from clouding to coma; reduced ability to direct,
focus, sustain, and shift attention);
(b) Global disturbance of cognition (perceptual distortions,
illusions and hallucinations - most often visual; impairment of
abstract thinking and comprehension, with or without
transient delusions, but typically with some degree of
incoherence; impairment of immediate recall and of recent
memory but with relatively intact remote memory;
disorientation for time as well as, in more severe cases, for
place and person);

ICD 10
(c) Psychomotor Disturbances (hypo- or hyperactivity and
unpredictable shifts from one to the other; increased reaction time;
increased or decreased flow of speech; enhanced startle reaction);
(d) Disturbance of the sleep-wake cycle (insomnia or, in severe
cases, total sleep loss or reversal of the sleep-wake cycle; daytime
drowsiness; nocturnal worsening of symptoms; disturbing dreams
or nightmares, which may continue as
hallucinations after awakening)
(e) Emotional disturbances e.g. depression, anxiety or fear,
irritability, euphoria, apathy or wondering perplexity.
The onset is usually rapid, the course diurnally fluctuating, and the
total duration of the condition less than 6 months.

ICD 10
F05 Delirium, not induced by alcohol and other

psychoactive substances
F05.0 Delirium, not superimposed on dementia,
F05.1 Delirium, superimposed on dementia
F05.8 Other delirium
F05.9 Delirium, unspecified

DSM IV TR

A) Disturbance of consciousness (i.e., reduced clarity of

awareness of the environment) with reduced ability to focus,

sustain, or shift attention.
B) A change in cognition (such as memory deficit,

disorientation, language disturbance) or the development of a

perceptual disturbance that is not better accounted for by a
preexisting, established, or evolving dementia.
C) The disturbance develops over a short period of time

(usually hours to days) and tends to fluctuate during the course

of the day.
D) There is evidence from the history, physical examination, or

laboratory findings that the disturbance is caused by the direct

physiological consequences of a general medical condition

DSM-IV-TR Classification of Delirium

Delirium due to a general medical condition (indicate

the condition)
Substance intoxication delirium
Substance withdrawal delirium
Delirium due to multiple etiologies (indicate the

etiologies)
Delirium not otherwise specified

Sub types

Hyperactive
Hypoactive
Mixed

Hyperactive:
Three or more of the following: hypervigilance, restlessness, fast or
loud speech, anger or irritability, combativeness, impatience,
uncooperativeness, swearing, singing, laughing, euphoria, wandering,
easy startling, distractibility, nightmares, persistent thoughts.
b) Hypoactive:
Patients were classified as hypoactive subtype if they had four or
more of the following: unawareness, decreased alertness, sparse or
slow speech, lethargy, decreased motor activity, staring, apathy.
c) Mixed:
Met the criteria for both (a) and (b) above.
a)

Course
The symptoms of delirium usually develop over hours to days,

although in some individuals they may begin abruptly (e.g., after a

head injury).
More typically, prodromal symptoms such as restlessness, anxiety,

irritability, disorientation, distractibility or sleep disturbance,

progress to full-blown delirium within a 1- to 3-day period.
The delirium may resolve in a few hours to days, or symptoms may

persist for weeks to months particularly in elderly and individuals

with coexisting dementia.
If the underlying etiological factor is promptly corrected or is self

limited, recovery is more likely to be complete and more rapid

course
Individuals with better premorbid cognitive and physical

functioning have better recovery from delirium.

Those with previous episodes of delirium may be at increased
risk for recurrent symptoms.
Persistent cognitive deficits are also common in elderly
individuals recovering from delirium.
Delirium is also associated with increased functional decline and
risk of institutional placement.
The mortality rates among hospitalized patients with delirium
range from 22 to 76 percent.
The 1-year mortality rate associated with cases of delirium is 35
to 40 percent.

Differential diagnosis
Delirium should be distinguished from other organic

syndromes, especially dementia

Memory impairment is common to both delirium and
dementia, but the person with dementia does not have
the disturbance in consciousness.
The temporal onset and course of cognitive impairment
are helpful in distinguishing between delirium and
dementia.
Delirium results from the direct physiological effects of a
drug of abuse, Substance Intoxication Delirium or
Substance Withdrawal Delirium

Differential diagnosis
Brief Psychotic Disorder, acute state in Schizophrenia,

Schizophreniform Disorder, and other Psychotic Disorders.

- In delirium, the psychotic symptoms are fragmented and
unsystematized.
Mood Disorders and Anxiety Disorders.
Acute Stress Disorder

Differential diagnosis
Delirium must be distinguished from Malingering and from

Factitious Disorder.- This distinction is made based on the often

atypical presentation in Malingering and Factitious Disorder and
the absence of a general medical condition or substance that is
etiologically related to the apparent cognitive disturbance.
Cognitive disorder not otherwise specified.

MANAGEMENT

Initial Evaluation
History with special attention to medications
General physical examination and neurologic examination
Complete blood count
Electrolyte panel including calcium, magnesium,

phosphorus
Liver function tests including albumin
Renal function tests

Further evaluation- first tier

Systemic infection screen
Urinalysis and culture
Chest radiograph
Blood cultures
Electrocardiogram
Arterial blood gas
Serum and/or urine toxicology screen (perform earlier in young

persons)
Brain imaging with MRI with diffusion and gadolinium (preferred)
or CT
Suspected CNS infection: lumbar puncture following brain imaging
Suspected seizure-related etiology: electroencephalogram (EEG) (if
high suspicion should be performed immediately)

Second tier

Vitamin levels: B12, folate, thiamine

Endocrinologic laboratories: thyroid-stimulating hormone (TSH)

and free T4; cortisol

Serum ammonia
Sedimentation rate
Autoimmune serologies: antinuclear antibodies (ANA),
complement levels; p-ANCA, c-ANCA
Infectious serologies: rapid plasmin reagin (RPR);
fungal and viral serologies if high suspicion; HIV antibody
Lumbar puncture (if not already performed)
Brain MRI with and without gadolinium (if not already performed)

EEG
Slowing of posterior dominant rhythm
Increased generalized slow wave activity
Magnitude of change in frequency of posterior dominant rhythm is

more important than absolute frequency

Cross-sectional QEEG is potentially useful in the early differential
diagnosis of encephalopathy
Variables which collectively distinguished delirium from dementia

EEG theta activity

Relative power in delta

Brain map rating

SCALES

MMSE
Confusion assessment method
Richmond agitation sedation scale
Informant questionnaire on cognitive decline in elderly

Severity of Delirium

Organic brain syndrome scale

The memorial delirium rating scale
Delirium rating scale revised

Management
Treatment of the underlying inciting factor
Supportive care - Reorientation by the nursing staff and family

combined with visible clocks, calendars and outside-facing

windows can reduce confusion.
Sensory isolation should be prevented by providing glasses and

hearing aids to those patients who need them.

Sundowning can be addressed to a large extent through vigilance

to appropriate sleep-wake cycles.

During the day, a well-lit room should be accompanied by

activities or exercises to prevent napping.

Cont ..
At night, a quiet, dark environment with limited interruptions

by staff can assure proper rest.

Maintaining proper nutrition and volume status
Managing incontinence and skin breakdown.
Bed alarms and personal sitters are less disorienting than

physical restraints.

Pharmacotherapy
Typicals(haloperidol)) are main stay of treatment
Oral/iv/
Side effect cardiac arrhythmia ,look for QTC

prolongation
Dose 1-2mg po. q4h.
Atypicals Risperidone, Olanzapine

Pharmacotherapy
Risperidone :0.51 mg a day
EPS concerns
Limited data in Delirium
Olanzapine : 510 mg a day
Metabolic syndrome
Higher mortality in dementia
Quetiapine : 25150 mg a day
More sedating Patients
Benzodiazepine
Lorazepam : 0.53 mg a day and as needed every 4 hr
Respiratory depression, paradoxical agitation
Best use in delirium secondary to alcohol/benzodiazepine withdrawal

ECT is also a treatment for delirium when other approaches have failed

Treatment of Specific Etiologies of

Delirium
Anticholinergic Intoxication
Anticholinergic poisoning almost always results in

delirium and is often accompanied by physical agitation

and visual hallucinations.
Physical signs - dilated, poorly reactive pupils; warm,

dry skin; dry mouth; fever; tachycardia; elevated blood

pressure; constipation; and urinary retention.
Use of cholinesterase inhibitors, such as physostigmine,

has been shown to reduce the severity of the delirium

but requires repeated dosing because of a short half-life.

Treatment of Specific Etiologies of

Delirium
Wernicke's Encephalopathy
It is characterized by nystagmus and ophthalmoplegia,

mental-status changes, and unsteadiness of stance and

gait.
The disorder results from a deficiency in vitamin B 1

(thiamine)
Wernicke's encephalopathy is a medical emergency,

thiamine should be initiated immediately, either

intravenously or intramuscularly.
Substance Intoxication
Substance Withdrawal

Treatment in Special Populations

Parkinson's Disease
Parkinson's disease patients are predisposed to delirium.
In Parkinson's disease - the antiparkinsonian agents are

frequently implicated in causing delirium.

Decreasing the dosage of the antiparkinsonian agent has to be
weighed against a worsening of motor symptoms.
If the antiparkinsonian agents cannot be further reduced or if the
delirium persists after attenuation of the antiparkinsonian
agents, clozapine is recommended.
Terminally Ill Patients
The focus may change from an aggressive search for the etiology
of the delirium to one of palliation, comfort, and assistance with
dying.

Yale Delirium Prevention Trial demonstrated the

effectiveness of intervention protocols targeted toward six

risk factors:
Orientation and therapeutic activities for cognitive

impairment
Early mobilization to avert immobilization
Nonpharmacologic approaches to minimize the use of

psychoactive drugs

Interventions to prevent sleep deprivation,

Communication methods adaptive equipment

(particularly eyeglasses and hearing aids) for vision,

hearing impairment,
Early intervention for volume depletion

Burden of delirium
Increased nursing care
Increased length of stay
Increased risk of cognitive decline
Increased risk of functional decline
Increased mortality
Delay in postoperative mobilization
Prevention of early rehabilitation
Increased need for home care services
Increased distress to caregivers
Barrier to psychosocial closure in terminally ill patient.

End results of delirium

Delirium result in direct neuronal injury
Neuronal injury markers may be particularly helpful

for identifying individuals at higher risk for dementia

after an episode of delirium

Dsm v
A. Disturbance in level of awareness and reduced ability

to direct, focus, sustain, and shift attention.

B. A change in cognition (such as deficits in orientation,

executive ability, language, visuoperception, learning

and memory)
-Cannot be assessed in face of severely reduced level of

awareness

-Should not be better accounted for by a preexisting

neurocognitive disorder
C. There is evidence from the history, physical

examination, or laboratory findings that the disturbance is

caused by the direct physiologic consequences of a general
medical condition.
D. The disturbance develops over a short period of time

(usually hours to a few days) and tends to fluctuate in

severity during the course of a day.

Note: The following supportive features are

commonly present in delirium but are not key

diagnostic features: sleep-wake cycle disturbance,
psychomotor disturbance, perceptual disturbances
(e.g., hallucinations, illusions), emotional
disturbances, delusions, labile affect, dysarthria and
EEG abnormalities (generalized slowing of
background activity)

Coding note: If delirium is superimposed on a pre-

existing Neurocognitive Disorder, indicate the delirium

as follows: _______
If the full criteria are currently met for delirium, specify

its current clinical status and/or features:

Hyperactive, hypoactive or mixed
Short term vs. persistent duration

CONCLUSIONS

Current research evidence on impairment of attention

Several structural assessment available as research tool
Pathophysiology is poorly understood
Neuroimaging is likely to show promising results in

elucidating pathophysiology
Current emphasis is on prevention of delirium
Paucity of literature from India

Thank you