Delirium

Moderator : Dr. M. Amir

Usmani

DELIRIUM

Presented by : Dr. Karrar

Husain

INTRODUCTION

HISTORY

INTRODUCTION

Delirium is an acute transient disturbance in consciousnessthat is characterized by a change in cognition manifestprimarily by an impairment of attention.

The patient's inability to focus, sustain, or shift attention canresult 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 anunderlying dementia.

These changes fluctuate considerably during a 24-hour periodand 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

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HISTORY

Hippocrates - 5th century BC- a clinical entity, poor prognosticsign.

Celsus, 1st century - first to use the term delirium anddistinguished it from hysteria, depression, and mania.

The term delirium originates from latin word delirio –to becrazy.

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2nd century AD, Galen differentiated between primary andsecondary types of delirium.

19th century emphasis was placed on disturbed consciousnessas the hallmark of delirium.

George angel and romano – 19th century, demonstrated thatdelirium 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 deliriumwere made in the 1987 revision of the manual, DSM-IIIR.

The 1994 revision, DSM-IV, divides the criteria for diagnosingdelirium into five separate categories

DSM 5……

EPIDEMIOLOGY

ETIOLOGY

NEUROPATHOLOGY

EPIDEMIOLOGY

There have been relatively few studies of the incidence andprevalence of delirium.

Little is known about the epidemiology of delirium incommunity or other non patient, non-institutionalizedpopulations.

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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 ashigh as 80% (Riker et al, 2009)

13–28% patients with ischemic stroke, subarachnoidhemorrhage 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 isassociated with increased short term and 6-month mortality,increased mechanical ventilation days, longer ICU stay, andhospital 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 andaround 10% of delirious general hospital patients receive apsychiatric 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 afterdischarge.

Higher rate of mortality than do nondelirious patients withthe 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 andtherapy, and thus further complicating their underlyingmedical condition.

RISK FACTORS

Risk for delirium could be conceptualized into twocategories :

1. Pre-disposing

2. Precipitating factors

Managing predisposing factors for delirium becomes essentialin decreasing future episodes of delirium and the morbidityand mortality associated with it.

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PRE-DISPOSING

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PRE-DISPOSING

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PRECIPITATING FACTORS

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Practically any physiologic derangement can cause delirium ina susceptible individual.

As currently conceptualized, delirium is a thresholdphenomena, where systemic and cerebral insults arecumulative.

In a prospective study of delirium in elderly patients, Francisand 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 improvingpatient outcome and reduce the cost of caring for deliriouspatients

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 DAand glutamate, whereas they that of Ach.

Hypoxia, DA and Ach

GABA

Delirium in conditions that either (e.g. hepaticencephalopathy) 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 andwithdrawal from serotonergic drugs .

(Vander Mast, 1994).

Histamine

Antihistamines (H1 antagonists) are associated with deliriumesp. in the elderly. They also increase catechols and serotoninas possible mechanisms for delirium. (Tejera, 1994)

H2 blockers – associated with delirium, mechanism isuncertain, probably anticholinergic action. (Jones, 1986)

Glutamate

Glutamate excitatory neurotoxicity via NMDA receptor apoptosis and neuronal death associated with alcoholintoxication and withdrawal, delirium.

NMDA antagonists, such as phencyclidine (PCP) andketamine, are also associated with delirium

Cytokines

Delirium from inflammatory or infectious causes.

(Manos, 1995; Ovsiew, 1995).

Therapeutic administration of some cytokines, such asinterferons and interleukins has been reported to causedelirium, perhaps related to d b-b-b permeability.

Cytokines may influence activity of neurotransmittersystems, 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 neurocognitivedisorders, which consist of delirium, major NCD, mild NCDand their etiological subtypes.

In ICD 10- F00-F09 Organic, including symptomatic, mentaldisorders.. F05

F10-F19 Mental and behavioural disorders due topsychoactive 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 (reducedorientation to the environment).

B. The disturbance develops over a short period of time (usuallyhours to a few days), represents a change from baselineattention and awareness, and tends to fluctuate in severityduring 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 explainedby another preexisting, established, or evolvingneurocognitive disorder and do not occur in the context of aseverely reduced level of arousal, such as coma.

E. There is evidence from the history, physical examination, orlaboratory findings that the disturbance is a directphysiological consequence of another medical condition,substance intoxication or withdrawal (i.e., due to a drug ofabuse or to a medication), or exposure to a toxin, or is due tomultiple 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 rapidand unpredictable shift from one state to another.

OTHERS - Other specified delirium, Unspecified delirium

ICD-10

F05 Delirium, not induced by alcohol and other psychoactivesubstances

• 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 OTHERPSYCHOACTIVE SUBSTANCES

A. Clouding of consciousness, i.e. reduced clarity of awareness ofthe environment, with reduced ability to focus, sustain, orshift attention.

B. Disturbance of cognition, manifest by both:

1. impairment of immediate recall and recent memory, withrelatively 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 atleast one of the following:

1. insomnia, which in severe cases may involve total sleep loss,with or without daytime drowsiness, or reversal of thesleep-wake cycle;

2. nocturnal worsening of symptoms;

3. disturbing dreams and nightmares which may continue ashallucinations or illusions after awakening.

E. Rapid onset and fluctuations of the symptoms over the courseof the day.

F. Objective evidence from history, physical and neurologicalexamination or laboratory tests of an underlying cerebral orsystemic disease (other than psychoactive substance-related)that can be presumed to be responsible for the clinicalmanifestations 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 withhistory of prior psychiatric illness

Patient described as “confused” or “disoriented”

Diffuse slow waves or epileptiform discharges onelectroencephalogram.

SCALES

Confusion Assessment Method (CAM) and CAM-ICU forcritically 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

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COURSE AND PROGNOSIS

By the third hospital day, approximately one-half the patientswho are diagnosed with delirium have been diagnosed.

Symptoms of delirium usually last 3 to 5 days, but there isslow resolution of symptoms contributing to persistentsymptoms of delirium at 6 to 8 weeks for severely ill patients.

Symptom resolution is frequently incomplete by hospitaldischarge, with as many as 15 percent of patients remainingsymptomatic of delirium at 6 months.

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In general, studies suggest that the increased mortality riskassociated with delirium was maintained at 12, 24, and 36months with a risk ratio of at least 2 at all time points.

Additionally, at 24 months, the increased risk of cognitive andfunctional impairment remained.

PREVENTION

MANAGEMENT

PREVENTION

Primary prevention

Minimization of polypharmacy.

Anti cholinergic, hypnosedative and opioid medicationsshould be used sparingly in the elderly.

Maintain hydration and nourishment and ensure sufficientsleep.

Caregivers and nursing staff must be trained to recognizedelirium.

Secondary prevention

Early diagnosis and treatment

Improved recognition of the condition.

It is recommended that all acutely ill elderly patients shouldhave a brief mental test on admission to increase the rate ofdetection of delirium.

Environment modifications, close monitoring to preventfurther morbidity and mortality.

(Jitapunkul et al,

1992).

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 withdelirium 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 isdirected 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 suspectedtrauma);

• Cerebrospinal fluid examination.

In the future, a measure of total serum anticholinergicactivity may prove helpful in deciding whether to discontinuesome or all medications.

This is a radioreceptor assay that has been validated atseveral centers; however, it is not yet available commercially.

EEG

• Slowing of the posterior dominant rhythm and increasedgeneralized slow-wave activity.

• As delirium worsens and as the EEG background rhythmreaches 5 to 6 Hz or less, reactivity is lost.

• The magnitude of change in frequency of the posteriordominant rhythm is more important than the absolutefrequency.

NEUROIMAGING : Structural brain imaging may detect acuteor 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 yourrole 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 daytime activity and environmental cues (such as windows andclocks).

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 beenestablished, a regular dose should be prescribed.

• Maintain at an effective dose and discontinue 7–10 days aftersymptoms resolve.

Maudsley prescribing

guidelines

Psychoactive medications are indicated for deliriumassociated with drug withdrawal or for behaviors that pose asafety risk for the patient and others.

Two general classes of agents—

• Antipsychotics and

• Benzodiazepines

Antipsychotics are effective in alleviating a range of deliriumsymptoms in patients with either hypoactive or hyperactiveclinical profiles.

The therapeutic impact is due to their sedative effects and byeffects on the dopamine-acetylcholine balance.

(Platt et al, 1994).

Haloperidol is the preferred drug because it is potent and hasfewer 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 approvedby 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 sideeffects when used intravenous.

IV haloperidol does not interfere with dopamine-inducedincreases 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 asneeded

IM 0.5–1 mg, observe for 30–60 minutes and repeat ifnecessary (peak effect: 20–40 minutes)

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Second-generation antipsychotics, such as risperidone,clozapine, olanzapine, quetiapine, ziprasidone, andaripiprazole, may be considered.

But these agents are associated with increased mortality inpatient of dementia.

For patients with Parkinson's disease and delirium whorequire antipsychotic medications, clozapine or quetiapinehave some support in the literature.

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

Benzodiazepines are also used in the management ofdelirium to sedate the agitated patient.

When the agitation is associated with sedative-hypnotic andalcohol withdrawal, benzodiazepines are the treatment ofchoice.

Dosing : Lorazepam –0.5–3 mg a day and as needed every4hr.

BZD may worsen delirium and may cause respiratorydepression.

Cholinestrase inhibitors

Donezepil 5mg OD, very little evidence

Rivastigmine 3-9 mg OD, very little experience, usually usedin 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 whenantipsychotics and benzodiazepenes are not effective.

Maudsley prescribing

guidelines

Electroconvulsive Therapy

It has been used as a last resort for delirious patients withsevere 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.





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 ortrazodone, to reset the sleep–wake cycle may be appropriate.

AFTER CARE:

Many patients are discharged before their symptoms are fullyresolved.

Problems with attention and orientation are especiallypersistent (Levkoff et al, 1994).

Depression, post traumatic stress disorder (PTSD) arerecognized as psychological sequelae.

CONCLUSION

• Delirium is complex neuropsychiatric syndrome that iscommon in all health care settings.

• The field is hampered by poor detection.

• Psychiatrists can play a pivotal role in the diagnosis andtreatment of delirious patients.

• Typical neuroleptic drugs remain the cornerstone oftreatment.

• Cognitive impairment of delirium is not entirely reversible inall patients.

• During delirium there is significant risk for progression ofunderlying dementia.

• Symptoms of delirium frequently persists beyond the acutephase of treatment, therefore post-discharge treatment plansmust focus on reducing ongoing risk factors and managingresidual functional impairment.

Thank

you

Health & Medicine

Delirium