Delirium

Moderator : Dr. M. Amir
DELIRIUM
Presented by : Dr. Karrar
Husain

INTRODUCTION
 Delirium is an acute transient disturbance in consciousness
that is characterized by a change in cognition manifest
primarily by an impairment of attention.
 The patient's inability to focus, sustain, or shift attention can
result in the impairment of other neurobehavioral tasks (e.g.,
memory).
 Language and visual spatial skills also can be affected.
Lipowski Z: Delirium: Acute confusional states. New York, Oxford University Press,
1990
Lipowski Z: Delirium (Acute confusional states). JAMA 258:1789, 1987

 Changes in cognition seen in delirium are not explained by an
underlying dementia.
 These changes fluctuate considerably during a 24-hour period
and tend to be more pronounced at night.

 Intensive care unit psychosis
 Acute confusional state
 Acute brain failure
 Encephalitis
 Encephalopathy
 Toxic metabolic state
 Central nervous system toxicity
 Cinchonism
 Paraneoplastic limbic encephalitis
 Sundowning
 Cerebral insufficiency
 Organic brain syndrome
CTP 9th ed

HISTORY
 Hippocrates - 5th century BC- a clinical entity, poor prognostic
sign.
 Celsus, 1st century - first to use the term delirium and
distinguished it from hysteria, depression, and mania.
 The term delirium originates from latin word delirio –to be
crazy.
CTP 9th ed

 2nd century AD, Galen differentiated between primary and
secondary types of delirium.
 19th century emphasis was placed on disturbed consciousness
as the hallmark of delirium.
 George angel and romano – 19th century, demonstrated that
delirium is due to reduction in metabolic activity
 The first modern standardized criteria for the diagnosis -DSM,
3rd edition (DSM-III) published in 1980.
Levkoff S, Marcantonio E: Delirium: A major diagnostic and therapeutic challenge for
clinicians caring for the elderly. Comp Ther 20:550, 1994
Lipowski Z: Delirium: Acute confusional states. New York, Oxford University Press,
1990

 Substantial alterations of the diagnostic criteria for delirium
were made in the 1987 revision of the manual, DSM-IIIR.
 The 1994 revision, DSM-IV, divides the criteria for diagnosing
delirium into five separate categories
 DSM 5……

EPIDEMIOLOGY
ETIOLOGY
NEUROPATHOLOGY

EPIDEMIOLOGY
 There have been relatively few studies of the incidence and
prevalence of delirium.
 Little is known about the epidemiology of delirium in
community or other non patient, non-institutionalized
populations.

 Among the elderly :
 10-15% have delirium on admission
 10-40% develop delirium during the course of their hospital
(Bucht et al, 1999; Fann, 2000).

 Prevalence of delirium in different populations
General population: 0.4%
General population (>55 yrs): 1.1%
General hospital admissions: 9-30%
Elderly general hospital admissions: 5-55%
Elderly accident and emergency attenders: 16%
(Meagher, 2001)

AIDS: 17-40%
Cancer patients (terminal stages): 25-40%
Postoperative patients: 5-75%
ICU patients: 12-50%
Nursing home residents : 60%
(Meagher, 2001)

 In patients undergoing mechanical ventilation prevalence as
high as 80% (Riker et al, 2009)
 13–28% patients with ischemic stroke, subarachnoid
hemorrhage or intracerebral hemorrhage have delirium.
(Caeiro et al, 2004, McManus et al, 2009; Sheng et al, 2006)
 In critically ill patients on mechanical ventilation it is
associated with increased short term and 6-month mortality,
increased mechanical ventilation days, longer ICU stay, and
hospital stay. (Ely et al, 2004, Lat et al, 2009,Shehabi et al,2010)

 Delirium is common in patients referred to consultation-
liaison psychiatry services.
 10% of consultation-liaison referrals have delirium and
around 10% of delirious general hospital patients receive a
psychiatric consultation
(Sirois, 1988; Francis et al, 1990).

SIGNIFICANCE
 Increased healthcare cost –
• longer hospitalizations,
• increased requirements for nursing care and supervision,
• increased incidence of nursing home placement after
discharge.
 Higher rate of mortality than do nondelirious patients with
the same underlying medical condition.

 Delirious patients pose a potential medico legal risk –
1. informed consent;
2. risk to escape;
3. aggressive behavior;
4. risk for falls or self-injury.
 They are poorly cooperative with necessary procedures and
therapy, and thus further complicating their underlying
medical condition.

RISK FACTORS
 Risk for delirium could be conceptualized into two
categories :
1. Pre-disposing
2. Precipitating factors
 Managing predisposing factors for delirium becomes essential
in decreasing future episodes of delirium and the morbidity
and mortality associated with it.

CTP 9th ed
PRECIPITATING FACTORS

 Practically any physiologic derangement can cause delirium in
a susceptible individual.
 As currently conceptualized, delirium is a threshold
phenomena, where systemic and cerebral insults are
cumulative.

 In a prospective study of delirium in elderly patients, Francis
and colleagues identified five leading causes of delirium.
1. Fluid/electrolyte disturbance
2. Infection
3. Medication toxicity
4. Metabolic derangement
5. Sensory and environmental disturbance

 Protective factors
 Good premorbid functioning before delirium.
 Early recognition have a significant impact on improving
patient outcome and reduce the cost of caring for delirious
patients

NEUROPATHOPHYSIOLOGY
 Anatomical areas
 Prefrontal cortex,
 Right cerebral hemisphere (esp. parietal), and
 Sub cortical nuclei (esp. right sided thalamus & caudate).
(Trzepacz, 1994)

NEUROTRANSMISSION
 Cholinergic,
 Dopaminergic,
 Serotonergic And GABA-ergic Systems With NA,
 Glutaminergic,
 Opiatergic And Histaminergic Systems.

 ACETYLCHOLINE - decreased
• Anti cholinergic medications
• B1 deficiency
• Hypoxia  Ach.
• Hypoglycemia
 Experimental delirium

 DA:
 Increased Dopamine activity
 Administration of anti DA-ergic drugs treat delirium
 Delirium from intoxication with DA ergic drug (L-dopa,
dopamine, bupropion).
 Opiates, common cause of delirium, increase activity of DA
and glutamate, whereas they  that of Ach.
 Hypoxia,  DA and Ach 

 GABA
 Delirium in conditions that either  (e.g. hepatic
encephalopathy) or  (e.g. hypnosedative withdrawal).
 5HT
 Postulated as either  or  in different types of delirium: 
hepatic encephalopathy and serotonin syndrome
 Decreased in post cardiotomy patients with delirium and
withdrawal from serotonergic drugs .
(Vander Mast, 1994).

 Histamine
 Antihistamines (H1 antagonists) are associated with delirium
esp. in the elderly. They also increase catechols and serotonin
as possible mechanisms for delirium. (Tejera, 1994)
 H2 blockers – associated with delirium, mechanism is
uncertain, probably anticholinergic action. (Jones, 1986)

 Glutamate
 Glutamate excitatory neurotoxicity via NMDA receptor 
apoptosis and neuronal death associated with alcohol
intoxication and withdrawal, delirium.
 NMDA antagonists, such as phencyclidine (PCP) and
ketamine, are also associated with delirium

 Cytokines
 Delirium from inflammatory or infectious causes.
(Manos, 1995; Ovsiew, 1995).
 Therapeutic administration of some cytokines, such as
interferons and interleukins has been reported to cause
delirium, perhaps related to d b-b-b permeability.
 Cytokines may influence activity of neurotransmitter
systems, such as catecholamines, GABA and acetylcholine
(Rothwell, 1995)

 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.

DIAGNOSIS AND CF
DIFFERENTIAL
DIAGNOSIS
COURSE

CLASSIFICATION
 Delirium is classified in DSM 5 in chapter of neurocognitive
disorders, which consist of delirium, major NCD, mild NCD
and their etiological subtypes.
 In ICD 10- F00-F09 Organic, including symptomatic, mental
disorders.. F05
 F10-F19 Mental and behavioural disorders due to
psychoactive substance use with individual substance.
DSM 5
ICD-10

DSM 5
Diagnostic Criteria
A. A disturbance in attention (i.e., reduced ability to direct,
focus, sustain, and shift attention) and awareness (reduced
orientation to the environment).
B. The disturbance develops over a short period of time (usually
hours to a few days), represents a change from baseline
attention and awareness, and tends to fluctuate in severity
during the course of a day.
C. An additional disturbance in cognition (e.g., memory deficit,
disorientation, language, visuospatial ability, or perception).

D. The disturbances in Criteria A and C are not better explained
by another preexisting, established, or evolving
neurocognitive disorder and do not occur in the context of a
severely reduced level of arousal, such as coma.
E. There is evidence from the history, physical examination, or
laboratory findings that the disturbance is a direct
physiological consequence of another medical condition,
substance intoxication or withdrawal (i.e., due to a drug of
abuse or to a medication), or exposure to a toxin, or is due to
multiple etiologies.

 Specify whether
(1) substance intoxication delirium
(2) substance withdrawal delirium
(3) medication induced delirium
(4) delirium due to another medical condition
(5) delirium due to multiple etiologies

 Specify if
1. Acute – lasting a few hours or day
2. Persistent- lasting weeks or months
 Specify if
1. Hyperactive
2. Hypoactive
3. Mixed level of activity

 Associated feature supporting diagnosis :
• Disturbance in sleep wake cycle
• Emotional disturbance like anxiety, fear, depression,
euphoria, anger, irritability and apathy. There may be rapid
and unpredictable shift from one state to another.
 OTHERS - Other specified delirium, Unspecified delirium

ICD-10
 F05 Delirium, not induced by alcohol and other psychoactive
substances
• F05.0 Delirium, not superimposed on dementia, so described
• F05.1 Delirium, superimposed on dementia
• F05.8 Other delirium
• F05.9 Delirium, unspecified

 FO5 DELIRIUM, NOT INDUCED BY ALCOHOL AND OTHER
PSYCHOACTIVE SUBSTANCES
A. Clouding of consciousness, i.e. reduced clarity of awareness of
the environment, with reduced ability to focus, sustain, or
shift attention.
B. Disturbance of cognition, manifest by both:
1. impairment of immediate recall and recent memory, with
relatively intact remote memory;
2. disorientation in time, place or person.

C. At least one of the following psychomotor disturbances:
1. rapid, unpredictable shifts from hypo-activity to hyper-activity;
2. increased reaction time;
3. increased or decreased flow of speech;
4. enhanced startle reaction.

D. Disturbance of sleep or the sleep-wake cycle, manifest by at
least one of the following:
1. insomnia, which in severe cases may involve total sleep loss,
with or without daytime drowsiness, or reversal of the
sleep-wake cycle;
2. nocturnal worsening of symptoms;
3. disturbing dreams and nightmares which may continue as
hallucinations or illusions after awakening.

E. Rapid onset and fluctuations of the symptoms over the course
of the day.
F. Objective evidence from history, physical and neurological
examination or laboratory tests of an underlying cerebral or
systemic disease (other than psychoactive substance-related)
that can be presumed to be responsible for the clinical
manifestations in A-D.

Recognizing warning Signs of Delirium
 Acute change in mental status
 Presence of medical illness
 Visual hallucinations
 Fluctuating levels of consciousness
 Acute onset of psychiatric symptoms without prior history of
psychiatric illness

 Acute onset of new or different psychiatric symptoms with
history of prior psychiatric illness
 Patient described as “confused” or “disoriented”
 Diffuse slow waves or epileptiform discharges on
electroencephalogram.

SCALES
 Confusion Assessment Method (CAM) and CAM-ICU for
critically ill patients
 Severity of delirium –
1. Delirium Rating Scale (DRS),
2. Memorial Delirium Assessment Scale (MDAS)

DIFFERENTIAL DIAGNOSIS
 Depression
 Dementia
 Schizophrenia
 Adjustment disorders,
 Anxiety disorders,
 Agitated depression
 Mania
CTP 9th ed

COURSE AND PROGNOSIS
 By the third hospital day, approximately one-half the patients
who are diagnosed with delirium have been diagnosed.
 Symptoms of delirium usually last 3 to 5 days, but there is
slow resolution of symptoms contributing to persistent
symptoms of delirium at 6 to 8 weeks for severely ill patients.
 Symptom resolution is frequently incomplete by hospital
discharge, with as many as 15 percent of patients remaining
symptomatic of delirium at 6 months.
CTP 9th ed

 In general, studies suggest that the increased mortality risk
associated with delirium was maintained at 12, 24, and 36
months with a risk ratio of at least 2 at all time points.
 Additionally, at 24 months, the increased risk of cognitive and
functional impairment remained.

PREVENTION
 Primary prevention
 Minimization of polypharmacy.
 Anti cholinergic, hypnosedative and opioid medications
should be used sparingly in the elderly.
 Maintain hydration and nourishment and ensure sufficient
sleep.
 Caregivers and nursing staff must be trained to recognize
delirium.

 Secondary prevention
 Early diagnosis and treatment
 Improved recognition of the condition.
 It is recommended that all acutely ill elderly patients should
have a brief mental test on admission to increase the rate of
detection of delirium.
 Environment modifications, close monitoring to prevent
further morbidity and mortality.
(Jitapunkul et al,

MANAGEMENT
 Basic algorithm for initial delirium management
1. Taper or discontinue non-essential medications.
2. Close observation.
3. Monitor vital signs and fluid intake and outputs.
4. Complete history and perform initial laboratory studies.

5. Implement environment and psychosocial interventions.
6. Pharmacological treatment as indicated.
7. Physical restraints are used only as a last resort.

 Setting
 Considering the morbidity and mortality rates associated with
delirium and the need for its timely, definitive treatment,
inpatient care is almost always required.
 Definitive treatment is directed towards the condition(s)
causing the syndrome, whereas palliative treatment is
directed toward control of symptoms such as agitation.

LABORATORY EVALUATION
 Basic Laboratory Examination:
1. Complete blood count with differential,
2. Serum chemistries,
3. Urine analysis,
4. EKG,
5. Chest radiograph,
6. Pulse oxymetry-arterial blood gas.

 Additional Laboratories Based on History, Examination,
Laboratories:
• Serum-urine drug screens;
• Drug levels;
• Vitamin B12 ; folate;
• Thyroid tests;
• Ammonia levels;
• Blood-urine cultures;

• EEG (seizure disorder);
• CT or MR imaging (focal neurologic deficits or suspected
trauma);
• Cerebrospinal fluid examination.

 In the future, a measure of total serum anticholinergic
activity may prove helpful in deciding whether to discontinue
some or all medications.
 This is a radioreceptor assay that has been validated at
several centers; however, it is not yet available commercially.

 EEG
• Slowing of the posterior dominant rhythm and increased
generalized slow-wave activity.
• As delirium worsens and as the EEG background rhythm
reaches 5 to 6 Hz or less, reactivity is lost.
• The magnitude of change in frequency of the posterior
dominant rhythm is more important than the absolute
frequency.

 NEUROIMAGING : Structural brain imaging may detect acute
or subacute conditions, such as
• Subarachnoid hemorrhage,
• Subdural hematomas,
• Intracranial tumors, and
• Vascular changes, including stroke,
 may cause or contribute to a delirium.

NON PHARMACOLOGICAL INTERVENTION
 Ensure effective communication & reorientation (e.g.
explaining where the person is, who they are, and what your
role is)
 Promoting day activity
 Maintaining quite, well-lit environment
 Staff continuity
 Avoiding room and bed changes
 Providing hearing and visual aids

 Encouraging personal items
 Limiting visits especially for hyperactive delirium patients,
 Remove noxious stimuli (e.g., catheters, pumps, etc.)
 Normal sleep–wake cycles can be promoted by the use of day
time activity and environmental cues (such as windows and
clocks).
 Interruptions of sleep should be minimized when possible.
 Adequate nutrition.

PHARMACOLOGICAL INTERVENTION
General principles
• Keep the use of sedatives and antipsychotics to a minimum.
• Use one drug at a time.
• Titrate doses to effect.
• Review at least every 24 hours. Once an effective has been
established, a regular dose should be prescribed.
• Maintain at an effective dose and discontinue 7–10 days after
symptoms resolve.
Maudsley prescribing

 Psychoactive medications are indicated for delirium
associated with drug withdrawal or for behaviors that pose a
safety risk for the patient and others.
 Two general classes of agents—
• Antipsychotics and
• Benzodiazepines

 Antipsychotics are effective in alleviating a range of delirium
symptoms in patients with either hypoactive or hyperactive
clinical profiles.
 The therapeutic impact is due to their sedative effects and by
effects on the dopamine-acetylcholine balance.
(Platt et al, 1994).

 Haloperidol is the preferred drug because it is potent and has
fewer anti cholinergic and hypotensive side effects.
 Therapy should be monitored closely for side effects.
 Haloperidol can be administered through oral, intravascular,
intravenous routes though intravenous route is not approved
by US FDA.
(Adams 1984, 1988),

 Intravenous route
• Potency is twice that of oral dose.
• Fast onset of action (3-19 minutes)
• Elimination T ½ is 10-19 hours.
(Friedman, 1995).
(Gelfand, 1992)

 Advantages
 Relatively safe side-effect profile.
 Haloperidol has surprisingly infrequent extrapyramidal side
effects when used intravenous.
 IV haloperidol does not interfere with dopamine-induced
increases in renal blood flow
(Gelfand, 1985; Moulaert, 1989; Tesar, 1986);
Armstrong, 1986; Fernandez, 1988

 Dosing
 Oral 0.5–1 mg bd with additional doses every 4 hours as
needed
 IM 0.5–1 mg, observe for 30–60 minutes and repeat if
necessary (peak effect: 20–40 minutes)
CTP 9th ed

 Second-generation antipsychotics, such as risperidone,
clozapine, olanzapine, quetiapine, ziprasidone, and
aripiprazole, may be considered.
 But these agents are associated with increased mortality in
patient of dementia.
 For patients with Parkinson's disease and delirium who
require antipsychotic medications, clozapine or quetiapine
have some support in the literature.
CTP 9th ed

Advances in Psychiatric Treatment (2008), vol.
14, 292–301, BJPsych advances

 Benzodiazepines are also used in the management of
delirium to sedate the agitated patient.
 When the agitation is associated with sedative-hypnotic and
alcohol withdrawal, benzodiazepines are the treatment of
choice.
 Dosing : Lorazepam –0.5–3 mg a day and as needed every
4hr.
 BZD may worsen delirium and may cause respiratory
depression.

 Cholinestrase inhibitors
 Donezepil 5mg OD, very little evidence
 Rivastigmine 3-9 mg OD, very little experience, usually used
in chronic delirium as an adjunct to antipsychotics.
 Others
 Melatonin 2mg OD, used to correct sleep wake cycle
 Sodium valproate, some case reports of its use when
antipsychotics and benzodiazepenes are not effective.
Maudsley prescribing
guidelines

 Electroconvulsive Therapy
 It has been used as a last resort for delirious patients with
severe agitation who are not responsive to pharmacotherapy.
 The ECT is usually given en bloc or daily for several days,
sometimes with multiple treatments per day.

Advances in Psychiatric Treatment (2008), vol. 14, 292–
301, BJPsych advances

 Sleep–Wake Cycle
• Delirium is frequently complicated by changes in the sleep–
wake cycle.
• Sedating medicines – bedtime
• Stimulating medicines or caffeine in morning
• Brief, judicious use of sedating agents, such as zolpidem or
trazodone, to reset the sleep–wake cycle may be appropriate.

AFTER CARE:
 Many patients are discharged before their symptoms are fully
resolved.
 Problems with attention and orientation are especially
persistent (Levkoff et al, 1994).
 Depression, post traumatic stress disorder (PTSD) are
recognized as psychological sequelae.

CONCLUSION
• Delirium is complex neuropsychiatric syndrome that is
common in all health care settings.
• The field is hampered by poor detection.
• Psychiatrists can play a pivotal role in the diagnosis and
treatment of delirious patients.
• Typical neuroleptic drugs remain the cornerstone of
treatment.

• Cognitive impairment of delirium is not entirely reversible in
all patients.
• During delirium there is significant risk for progression of
underlying dementia.
• Symptoms of delirium frequently persists beyond the acute
phase of treatment, therefore post-discharge treatment plans
must focus on reducing ongoing risk factors and managing
residual functional impairment.

Delirium

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Delirium

Editor's Notes