DELIRIUM

PRESENTER : D r. VA R A D A P
C H A I R P E R S O N : D r. D R U H I N 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 Sundowning
Encephalopathy Cerebral insufficiency
ICU psychosis Organic brain syndrome
Toxic metabolic state
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 FAC TO R S
• Demographic characteristics
• Cognitive status
• Functional status
• Sensory impairment
• Decreased oral intake
• Drugs
• Co existing medical conditions
P R E C I P I TAT I N G FAC TO R S
• Drugs
• Primary neurological diseases
• Intercurrent illnesses – infections ,
iatrogenic complications ,sepsis,
anemia, poor nutrition
• Surgery – CABG, Orthopedic
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 derivatives
Heroin 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
HYPOTENSION 2)HYPOTHYROIDISM
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

5 CAROTID VESSELS BRUIT OR DECREASED PULSE TIA

6 SCALP AND FACE EVIDENCE OF TRAUMA

EVIDENCE OF NUCHAL
7 NECK RIGIDITY
MENINGITIS
PHYSICAL EXAMINATION
TUMOUR
PAPILLOEDEMA HYPERTENSIVE
ENCEPHALOPATHY
8 EYES
ANXIETY
PUPILLARY
DILATATION AUTONOMIC
HYPERACTIVITY

TONGUE OR CHEEK
9 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 STRENGTH ASYMMETRICAL CEREBROVASCULAR
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

NONPHARMACOLOGICAL
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.