DELIRIUM

PRESENTER : Dr. VARADA P

CHAIRPERSON : Dr. DRUHIN A V
PLAN
• Introduction
• Etymology
• History
• Nosology
• Criteria
• Risk factors
• Pathophysiology
• Types
• Management
• Recent developments
INTRODUCTION

Disorders of cognition are like Occam’s razor, challenging

clinicians with multiplicity, comorbidities and unclear
boundaries. Among them the most commonly met and often
unrecognized one is delirium which significantly complicates
prognosis and delivery of health care.
ETYMOLOGY

Origin- from Latin verb deliro- to be crazy

Derived from de + lira , a furrow (to go out of the furrow)
HISTORY

First description by Hippocrates in his Book of Epidemics –

astute observation of clinical features
Term first used by Celsus to describe a spectrum of disorders
ranging from general insanity to acute transient states of
disturbances including phrenitis,lethargus,hysteria,melancholia
and mania
Aretaeus of Cappadocia – phrenitis and lethargus as acute
manifestations of disease– first description of hypoactive and
hyperactive delirium
Philip Barrough (1583):- delirium as a derangement of
imagination,memory and cognition
Thomas Willis (1672):- elaborated this concept and identified
delirium as a set of symptoms, not a disease
Erasmus Darwin:- described delirium as a dream like state with
interruption of voluntary power and a suspension of the ability
to attend to one’s external environment
John Hunter:- defined delirium as a cessation of consciousness
of one’s own existence
James Sims:- delirium as distinct from general insanity,and that
it constituted an alienation of the mind;two types of delirium -
low and raving
Rees (1818):-insisted that delirium is a distinct condition with
two specific variants and a unique etiology that was localized
to the brain
George Engel and John Romano :- delirium due to reduction in
metabolic activities of brain,able to demonstrate it using EEG
COMPARATIVE NOSOLOGY

Acute confusional state CNS toxicity

Acute brain failure Paraneoplastic limbic
Encephalitis encephalitis
Encephalopathy Sundowning
ICU psychosis Cerebral insufficiency
Toxic metabolic state Organic brain syndrome
ICD 10 CRITERIA
Coded as F-05,Delirium not induced by alcohol or other psychoactive
substances

An etiologically nonspecific syndrome characterized by concurrent

disturbances of consciousness and
attention,perception,thinking,memory,psychomotor behavior,emotion
and the sleep wake cycle.

Variable duration-usually resolves by 4 weeks,may go upto 6 months

Maybe acute and subacute,

For a definite diagnosis,symptoms,mild or severe,should be
present in each one of the following areas

Impairment of consciousness and attention

Global disturbance of cognition
Psychomotor disturbances
Disturbances of sleep wake cycle
Emotional disturbances
Specifiers are
 Substance intoxication delirium
 Substance withdrawal delirium
 Medication induced delirium
 Delirium due to another medical condition
 Delirium due to multiple etiologies
Acute or persistent
Hyperactive, hypoactive or mixed
EPIDEMIOLOGY
• Common in elderly
• Rate varies based on settings
• Community studies- 1% of elderly population of age 55 or more
have delirium
• Elderly ER room subjects- 5-10% prevalence
• Mostly underdiagnosed
• Mortality -22 -76% in hospitalized patients
INCIDENCE AND PREVALENCE OF
DELIRIUM IN VARIOUS SETTINGS
RISK FACTORS FOR DELIRIUM
P R E D I S P O S I N G FA C T O R S P R E C I P I TAT I N G FAC T O R S

• Demographic characteristics • Drugs

• Cognitive status • Primary neurological
• Functional status diseases
• Sensory impairment • Intercurrent illnesses –
infections , iatrogenic
• Decreased oral intake
complications ,sepsis,
• Drugs anemia, poor nutrition
• Co existing medical • Surgery – CABG, Orthopedic
conditions surgeries
• Environmental factors
PROTECTIVE FACTORS

• Good premorbid functioning

• Interventions preventing delirium
• Focus on nutrition
• Increased rehabilitation
• Attention to visual and hearing impairment
PATHOPHYSIOLOGY
• Remains poorly understood
• Proposed theories include
1. Neurochemical alterations
2. Oxidative metabolism
3. Blood brain barrier alterations
4. Ammonia
NEUROCHEMICAL ALTERATIONS

1. Acetylcholine
2. Dopamine
3. Glutamate
4. GABA
5. Serotonin
ACETYL CHOLINE
• Evidence of cholinergic deficiency in delirium
• ACh involved in REM sleep , arousal , attention and memory
• Anticholinergic drugs worsen delirium
• Serum cholinergic deficiency was demonstrated
• Cholinergic agents like physostigmine improves delirium
DOPAMINE:
Dopaminergic excess
Probably due to regulatory influence on acetyl choline
Involvemnet in maintaining and shifting attention
Dopaminergic drugs(levodopa,bupropion)-causes delirium
Antidopaminergic drugs(antipsychotics) – used in treatment of
delirium
GLUTAMATE :
• causes delirium due to excitatory neurotoxicity effect through NMDA
receptors
• Proposed mechanism for Wernicke’s encephalopathy

GABA :
• Implicated in delirium secondary to benzodiazepine and alcohol
withdrawal
• Increased GABA levels in hepatic encephalopathy
Alterations in other neurotransmitters like norepinephrine ,
melatonin, serotonin- implicated in causation of delirium

 Maybe through their interactions with dopaminergic and

cholinergic pathways
OXIDATIVE METABOLISM

Disturbances in brain oxygen supply and demand

Impaired oxidative metabolism-predisposes to later

development of delirium
BLOOD BRAIN BARRIER ALTERATIONS

Hypothesized as a CNS response to systemic inflammation

during a state of blood brain barrier compromise
Post cardiac surgery patients- chemokine disrupts blood brain
barrier
Seen in patients following trauma ,primary
hyperparathyroidism and delirium tremens
AMMONIA

One of the factors causing hepatic encephalopathy

Ammonia – aggravates astrocyte swelling– cascade of events
leading to delirium
Elevated ammonia– increased glutamate and glutamine –
increased GABA – delirium
Cytokines like IL-1,IL-2,IL-6,TNF alpha and interferon –
increases permeability of BBB – alters neurotransmission
Chronic stress – activates sympathetic nervous system and
hypothalamo pituitary adrenocortical axis – increased cytokine
levels and chronic hypercorticolism –deleterious effects on
serotonin receptors
SUBSTANCES CAUSING DELIRIUM

Cocaine Gamma hydroxybutyrate

PCP Amphetamine and its
Heroin derivatives like Ecstasy
Alcohol Marijuana
Nitrous oxide flunitrazepam
SUBSTANCE WITHDRAWAL DELIRIUM

• Any acute change in mental status

• Supported by autonomic changes and detection of substance
or metabolite in serum or urine
Alcohol withdrawal :
classic agitated withdrawal – delirium tremens
Presents with delirium, autonomic hyperactivity and frequent
hallucinations
May progress to seizures and death
Benzodiazepine withdrawal :
presents like alcohol withdrawal with seizures
onset of symptoms depends upon half life of particular
benzodiazepine
Opiate withdrawal:

presents with severe flu like symptoms , gastro intestinal

cramping, diarrhea, diaphoresis, autonomic hyperactivity and
craving
delirium- with switching from transdermal fentanyl to morphine
POSTOPERATIVE DELIRIUM

• CABG : post CABG incidence –3 -35%

• Factors associated – increasing age
-- peripheral vascular disease
-- Preoperative IABP support
-- postoperative blood product usage
-- low cardiac output syndrome
-- hypertension ,smoking habbits ,
AF, pneumonia
Hip or joint replacement surgery :-
15-60% incidence
Cognitive impairment prior to surgery- high risk for delirium
Elective patients – less prone for delirium
CLINICAL FEATURES

• Rapid onset with variable and intermittent symptoms

• Can present with manic symptoms, anxiety like symptoms
,depression like symptoms or psychotic symptoms
• Maybe superimposed on other conditions
• Fluctuating course
• Sundowning
• Hallucinations, illusions and sensory misperceptions- 40%
• Typically visual hallucinations- ranging from dream like
experiences to terrifying visions
• Auditory, tactile and olfactory hallucinations – rare
• Persecutory delusions
• Reduced alertness- cardinal feature, manifested by maintaining
attention and focusing concentration
• Easily distractible
• Impaired memory-inability to register information and to retrieve
the information
• Problem solving, planning and guiding actions are affected
• Based on psychomotor activity – hypoactive, hyper active and
mixed

Hyperactive delirium:
• Most commonly recognized
• May exhibit agitation, psychosis and mood lability
• Refuse to cooperate with medical care
• Disruptive behavior
• May sustain injuries
Hypoactive delirium
• More common than hyperactive but less recognized
• Mostly associated metabolic causes
• Appear sluggish, lethargic as well as confused
• Disruptive, bizarre and injurious behavior absent
• Stronger stimuli needed for arousal
MIXED

• Have a mixture of symptoms of both hypo and hyper active

delirium
• More prone for morbidity and mortality
DIAGNOSIS
• Detailed history from caregiver
• Possibility for occult or atypical presentations
• Review of preadmission and current medications including
longstanding ones
• Occult alcohol or benzodiazepine use should be ruled out
PHYSICAL EXAMINATION
1)HYPOTHYROIDISM
2)INCREASED ICP
BRADYCARDIA
3)STOKES ADAM’S
SYNDROME
1 PULSE
1)HYPERTHYROIDISM
TACHYCARDIA 2)INFECTION
3)HEART FAILURE

1)SEPSIS
2 TEMPERATURE FEVER 2)THYROID STORM
3)VASCULITIS

1)SHOCK
2)HYPOTHYROIDISM
HYPOTENSION
3)ADDISON’S
DISEASE
BLOOD
3 PRESSURE
1)ENCEPHALOPATHY
HYPERTENSION 2)INTRACRANIAL
MASS
PHYSICAL EXAMINATION
1)DIABETES
2)PNEUMONIA
TACHYPNOEA 3)CARDIAC FAILURE
4)FEVER
5)ACIDOSIS
4 RESPIRATION

ALCOHOL OR OTHER
SHALLOW
SUBSTANCE INTOXICATION

BRUIT OR DECREASED
5 CAROTID VESSELS PULSE
TIA

6 SCALP AND FACE EVIDENCE OF TRAUMA

7 NECK EVIDENCE OF NUCHAL

RIGIDITY
MENINGITIS
PHYSICAL EXAMINATION
TUMOUR
PAPILLOEDEMA HYPERTENSIVE
ENCEPHALOPATHY
8 EYES
ANXIETY
PUPILLARY
DILATATION AUTONOMIC
HYPERACTIVITY

9 TONGUE OR CHEEK
MOUTH LACERATIONS
EVIDENCE OF GTCS

10 THYROID ENLARGED HYPERTHYROIDISM

INADEQUATE
CARDIAC OUTPUT
ARRHYTHMIA
POSSIBILITY OF
EMBOLI
11 HEART
HEART FAILURE
CARDIOMEGALY HYPERTENSIVE
DISEASE
PHYSICAL EXAMINATION
1)PRIMARY
PULMONARY FAILURE
12 LUNGS CONGESTION 2)PULMONARY
EDEMA
3)PNEUMONIA

ALCOHOL

13 BREATH

KETONES DIABETES

1)CIRRHOSIS
14 LIVER ENLARGEMENT
2)LIVER FAILURE
PHYSICAL EXAMINATION
MASS LESION
ASYMMETRY WITH CVA
BABINSKI’S SIGN PREEXISTING
DEMENTIA
REFLEXES

FRONTAL MASS
SNOUT
B/L PCA OCCLUSION

ABDUCENT WEAKNESS IN
INCREASED IN ICP
NERVOUS NERVE LATERAL GAZE
15
SYSTEM

MASS LESION
LIMB ASYMMETRICAL CEREBROVASCULAR
STRENGTH
DISEASE

ANXIETY
AUTONOMIC HYPERACTIVITY
DELIRIUM
LABORATORY EXAMINATION
DIFFERENTIAL DIAGNOSIS

• Dementia
• Depression
• Schizophrenia
• Anxiety
DIFFERENTIAL DIAGNOSIS
RATING SCALES

• CAM(confusion assessment method)

• Delirium rating scale (DRS)
• Memorial delirium rating scale (MDRS)
CONFUSION ASSESSMENT METHOD
MANAGEMENT

PHARMACOLOGICAL

MANAGEMENT OF
DELIRIUM

NONPHARMACOLOGICA
L
PHARMACOLOGICAL MANAGEMENT

• Addresses the brain dysfunction itself

• Underlying causes are separately considered
• Based upon prevailing notion of dopaminergic excess and
cholinergic deficiency as the principal neurochemical
aberrations
• Keep the use of sedatives and antipsychotics to a minimum.
• Use one drug at a time.
• Tailor doses according to age, body size and degree of agitation.
• Titrate doses to effect.
• Use small doses regularly, rather than large doses less frequently.
• Review at least every 24 hours.
• Increase scheduled doses if regular ‘as needed’ doses are
required after the initial 24-hour period.
• Maintain at an effective dose and discontinue 7–10 days after
symptoms resolve.
TYPICAL ANTIPSYCHOTICS
• Haloperidol : remains the standard agent to use in delirium
• Used in oral, intramuscular and intravenous routes
• Started in lower doses i.e. 0.25-0.5 mg every 4 hours, can be given up to 1-2 mg
every four hours(peak effect: 4–6 hours)
• IM 0.5–1 mg, observe for 30–60 minutes and repeat if necessary (peak effect: 20–40
minutes)
• Avoid IV dosage as much as possible
• Careful monitoring of ECG
• Maintaining serum potassium, calcium and magnesium levels
• Look or EPS
• Thioridazine, chlorpromazine and droperidol – effective,but higher anticholinergic
side effects
ATYPICAL ANTIPSYCHOTICS

• Risperidone ,olanzapine and quetiapine

• Equally effective as haloperidol with lesser EPS
• Risperidone – 0.5-1 mg per day
• Olanzapine -- 5-10 mg per day
• Quetiapine – 25-150 mg a day
BENZODIAZEPINES

• Either an alleviating agent or as a risk factor

• Can worsen the mental state in ICU and cancer patients
• Treatment of choice in agitation associated with sedative
hypnotic withdrawal like alcohol,BZD,barbiturates etc
• Lorazepam is preferred ( short duration of action)
• 0.5-3 mg a day and as needed every 4 hr
• Diazepam also can be used ,but worsening of symptoms
PROCHOLINERGIC AGENTS

• Intravenous physostigmine-in delirium due to toxicity with

anticholinergic drugs
• Dosage – 1-2 mg IV or IM with repeated doses in 30 minutes as
indicated
• Cholinesterase inhibitors: Donepezil and rivastigmine tried,but
no definite evidence
• SLEEP WAKE CYCLE:
• Judicious use of zolpidem or trazodone to reset the sleep wake
cycle

• ECT:
• When other approaches have failed
• Usually given en bloc or daily for several days, sometimes
multiple treatments per day
• Should be monitored closely
TREATMENT IN SPECIAL POPULATION
In Parkinson’s disease
• Often antiparkinsonian drugs are implicated
• Reducing the dosage of drugs
• If symptoms persists clozapine
• If not tolerated quetiapine is being tried
Terminally ill patients
• Focus is on palliation, comfort and assistance with dying
In those with concomitant dementia
• Both modalities are less effective
• Neuroleptics to be avoided in lewy body dementia and vascular
dementia
• Lower dose of antipsychotics should be used
• Monitoring of adverse effects
• Prolonged use should be avoided
NONPHARMACOLOGICAL
MANAGEMENT
• Treatment of underlying cause for delirium
• Maximizing safety of environment and providing psychosocial support
• Patient’s ability to interpret environment should not be affected-those with glasses
or hearing aid should be given those
• Paper and pen to improve communication if intubated
• Modifying the environment to reduce fear and agitation- avoid extremes of sensory
input
• Maintenance of patient comfort
• Adequate pain control
• Initiation of physical activity
Enhance orientation using visual cues like clock,calendar or
windows
Restoration of normal sleep wake cycle by daytime activity
Decreased interruption of sleep
Adequate nutrition
Psychosocial support by staff and family members (avoiding
unnecessary conversations near the patient, helping in
reorientation and reassurance
Minimal use of physical restraint
RECENT DEVELOPMENTS

Studies regarding alpha 2 agonists like clonidine and

dexmedetomidine – shows promising results that these may be
an acceptable alternative to opioids and GABA-ergic
medications in addressing the sedative, analgesic, and
hypnotic needs of critically ill patients in the ICU
• 5 HT antagonists like ondansetron- found to be useful in
delirium,esp in patients who have underwent cardiac surgeries
• Serotonin involvement in delirium
CONCLUSION

Delirium is a state of acute confusion and declined

cognitive functions which is often under diagnosed- as high as
65%. Multiple etiologies are found for delirium commonly being
infections and dyselectrolytemia. Identifying and treating
delirium helps reducing significant morbidity and mortality.
Usually delirium resolves by 2 weeks , but sometimes we do get
protracted delirium as well
REFERENCES
• Comprehensive textbook of psychiatry,9th edition
• Oxford textbook of psychiatry
• Adam and victor’s textbook of neurology
• The Maudsley’s prescribing guidelines- 12th edition
• Neerland BE, Hov KR, Bruun Wyller V, et al. The protocol of the Oslo Study
of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-
controlled trial. BMC Geriatrics. 2015;15:7. doi:10.1186/s12877-015-0006-3.