medicine 4.7 - confusion and delirium

CALDERON, GARCIA, HARDIN, MANABAT, SOLIS 1 of 8

PLM CM

CONFUSION AND DELIRIUM 4

Hi guys! This trans is purely Harrisons-based (18th ed.)

OUTLINE INTRODUCTION CLINICAL FEATURES OF DELIRIUM RISK FACTORS EPIDEMIOLOGY PATHOGENESIS APPROACH TO THE PATIENT: DELIRIUM o HISTORY o PHYSICAL EXAMINATION o ETIOLOGY o LABORATORY AND DIAGNOSTIC EVALUATION

TREATMENT: DELIRIUM PREVENTION

INTRODUCTION Confusion a mental and behavioral state of reduced

comprehension, coherence, and capacity to reason

one of the most common problems encountered in medicine

accounting for a large number of emergency department visits, hospital admissions, and inpatient consultations

Delirium an acute confusional state remains a major cause of morbidity and mortality

rates costing billions of dollars yearly in health care

costs in the United States alone often goes unrecognized despite clear evidence

that it is usually the cognitive manifestation of serious underlying medical or neurologic illness.

CLINICAL FEATURES OF DELIRIUM Delirium is a clinical diagnosis that can be made only at the

bedside. Terms used to describe delirium

encephalopathy acute brain failure acute confusional state postoperative or intensive care unit (ICU)

psychosis Manifestation many clinical manifestations

defined as a relatively acute decline in cognition that fluctuates over hours or days.

Hallmark of Delirium

a deficit of attention, although all cognitive domainsincluding memory, executive function, visuospatial tasks, and languageare variably involved.

Associated symptoms

altered sleep-wake cycles perceptual disturbances such as

hallucinations or delusions affect changes autonomic findings that include heart rate and

blood pressure instability Clinical categories

Two broad clinical categories: o Hyperactive Subtype

-Classic example: cognitive syndrome associated with severe alcohol withdrawal -prominent hallucinations, agitation, and

hyperarousal, often accompanied by life-threatening autonomic instability -easily recognized

o Hypoactive Subtype -Exemplified by: opiate intoxication -withdrawn and quiet, with prominent apathy and psychomotor slowing -overlooked more often -associated with worse outcomes

Based on differential psychomotor features A useful construct, but patients often fall

somewhere along a spectrum between the hyperactive and hypoactive extremes, sometimes fluctuating from one to the other within minutes.

Therefore, clinicians must recognize the broad range of presentations of delirium to identify all patients with this potentially reversible cognitive disturbance.

Reversibilty of delirium

Emphasized because many etiologies, such as systemic infection and medication effects, can be treated easily.

long-term cognitive effects of delirium remain largely unknown and understudied

Some episodes of delirium continue for weeks, months, or even years

In some instances, delirium does not disappear because there is underlying permanent neuronal damage.

Even after an episode of delirium resolves, there may be lingering effects of the disorder.

A patients recall of events after delirium varies widely, ranging from complete amnesia to repeated reexperiencing of the frightening period of confusion in a disturbing manner, similar to what is seen in patients with posttraumatic stress disorder.

Persistence and High recurrence rates

may be due to inadequate treatment of the underlying etiology of the syndrome

RISK FACTORS

Effective primary prevention strategy for delirium

begins with identification of patients at highest risk, including those preparing for elective surgery or being admitted to the hospital

no single validated scoring system has been widely accepted as a screen for asymptomatic patients

multiple well-established risk factors for delirium

Two Most consistently identified risks

older age and baseline cognitive dysfunction

Individuals who are over age 65 or exhibit low scores on standardized tests of cognition develop delirium upon hospitalization at a rate approaching 50%.

Its uncertain if the two is truly independent risk factors.

Other predisposing factors:

MEDICINE 1 // CONFUSION AND DELIRIUM 4


o sensory deprivation ( preexisting hearing and visual impairment)

o indices for poor overall health (baseline immobility, malnutrition, and underlying medical or neurologic illness)

In-hospital risks for delirium

use of bladder catheterization physical restraints sleep and sensory deprivation addition of three or more new medications Avoiding such risks remains a key

component of delirium prevention as well as treatment.

Development of postoperative delirium

Surgical and anesthetic risk factors: o specific procedures such as those

involving cardiopulmonary bypass o inadequate or excessive treatment of

pain in the immediate postoperative period

Relationship between delirium and dementia

complicated by significant overlap between the two conditions

not always simple to distinguish between them

serve as major risk factors for delirium: o Dementia o preexisting cognitive dysfunction

at least 2/3 of cases of delirium occur in patients with coexisting underlying dementia

Dementia with Lewy bodies

A form of dementia with parkinsonism characterized by:

o fluctuating course o prominent visual hallucinations o parkinsonism o attentional deficit that clinically

resembles hyperactive delirium.

Delirium in elderly

often reflects an insult to the brain that is vulnerable due to an underlying neurodegenerative condition

Development of delirium

sometimes heralds the onset of a previously unrecognized brain disorder.

EPIDEMIOLOGY

Delirium a common disease reported incidence has varied widely with the

criteria used to define the disorder Estimates of delirium in hospitalized patients

range from 14 to 56%, with higher rates reported for elderly patients and patients undergoing hip surgery.

Older patients in the ICU have especially high rates of delirium that range from 70 to 87%.

not recognized in up to 1/3 of delirious inpatients Delirium in the ICU:

o Diagnosis is problematic (cognitive dysfunction is often difficult to appreciate in the setting of serious systemic illness and sedation)

o should be viewed as an important manifestation of organ dysfunction not unlike liver, kidney, or heart failure.

Outside the acute hospital setting o delirium occurs in nearly 2/3 of patients in

nursing homes and in over 80% of those at

the end of life. These estimates emphasize the remarkably

high frequency of this cognitive syndrome in older patients, a population expected to grow in the upcoming decade with the aging of the baby boom generation.

In previous decades

an episode of delirium was viewed as a transient condition that carried a benign prognosis.

Now Delirium now has been clearly associated with

substantial morbidity rate and increased mortality rate and increasingly is recognized as a sign of serious underlying illness.

Recent estimates of in-hospital mortality rates among delirious patients have ranged from 25 to 33%, a rate similar to that of patients with sepsis.

Patients with an in-hospital episode of delirium have a higher mortality rate in the months and years after their illness compared with age-matched nondelirious hospitalized patients.

Delirious hospitalized patients have a longer length of stay, are more likely to be discharged to a nursing home, and are more likely to experience subsequent episodes of delirium; as a result, this condition has enormous economic implications.

PATHOGENESIS

Pathogenesis and anatomy of delirium

incompletely understood

Attentional deficit serves as the neuropsychological hallmark of delirium

appears to have a diffuse localization with the brainstem, thalamus, prefrontal cortex, and parietal lobes.

Focal lesions such as ischemic strokes rarely, have led to delirium in

otherwise healthy persons right parietal and medial dorsal

thalamic lesions have been reported most commonly, pointing to the relevance of these areas to delirium pathogenesis

Cortical and subcortical regions

Widespred disturbances in these regions cause delirium

Cause of delirium in most cases rather than a focal neuroanatomic cause

Electroencephalogram (EEG)

usually show symmetric slowing, a nonspecific finding that supports diffuse cerebral dysfunction, in persons with delirium

Acetylcholine deficiency

often plays a key role in delirium pathogenesis

Medications with anticholinergic

can precipitate delirium in susceptible individuals,

Therapies with cholinergic properties

designed to boost cholinergic tone e.x. cholinesterase inhibitors have, in small trials, been shown to

relieve symptoms of delirium Dementia patients susceptible to episodes of delirium

Those with Alzheimers pathology o known to have a chronic

cholinergic deficiency state due to degeneration of acetylcholine-producing



neurons in the basal forebrain

Dementia with Lewy bodies o Another common dementia

associated with decreased acetylcholine levels

o clinically mimics delirium in some patients

Other neurotransmitters

are also likely to be involved in this diffuse cerebral disorder

For example, increases in dopamine can also lead to delirium. o Patients with Parkinsons

disease treated with dopaminergic medications can develop a delirium-like state that features visual hallucinations, fluctuations, and confusion.

reducing dopaminergic tone with dopamine antagonists such as typical and atypical antipsychotic medications has long been recognized as effective symptomatic treatment in patients with delirium.

Not all individuals exposed to the same insult will develop signs of delirium

low dose of anticholinergic: o may have no cognitive

effects on a healthy young adult

o may produce a florid delirium in an elderly person with known underlying dementia.

extremely high dose of the same anticholinergic may lead to delirium even in healthy young persons.

This concept of delirium developing as the result of an insult in predisposed individuals is currently the most widely accepted pathogenic construct.

if a previously healthy individual with no known history of cognitive illness develops delirium in the setting of a relatively minor insult such as elective surgery or hospitalization, an unrecognized underlying neurologic illness such as a neurodegenerative disease, multiple previous strokes, or another diffuse cerebral cause should be considered.

delirium can be viewed as the symptom resulting from a stress test for the brain induced by the insult.

Exposure to known inciting factors

such as systemic infection and offending drugs

can unmask a decreased cerebral reserve

can herald a serious underlying and potentially treatable illness

APPROACH TO THE PATIENT: DELIRIUM Diagnosis clinical and is made at the bedside

careful history and physical examination is necessary in evaluating patients with possible confusional states

Screening tools

can aid physicians and nurses in identifying patients with delirium o Confusion Assessment Method (CAM) o Organic Brain Syndrome Scal o Delirium Rating Scale o Delirium Detection Score (in ICU) o ICU version of the CAM

These scales are based on criteria from the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM) or the World Health Organizations International Classification of Diseases (ICD)

These scales do not identify the full spectrum of patients with delirium.

Using CAM diagnosis of delirium is made if there is

acute onset and fluctuating course inattention accompanied by either disorganized thinking or altered level of consciousness.

Acutely confused patients

should be presumed delirious regardless of their presentation due to the wide variety of possible clinical features.

Not essential for diagnosis

A typical course that fluctuates over hours or days and may worsen at night (termed sundowning)

Observation Will reveal an altered level of consciousness or a deficit of attention.

Other hallmark features

alteration of sleep-wake cycles thought disturbances such as hallucinations or

delusions autonomic instability changes in affect.

HISTORY

Accurate history

difficult to elicit in delirious patients who have altered levels of consciousness or impaired attention

Information from collateral source

such as a spouse or another family member is invaluable.

3 Most important pieces of history

patients baseline cognitive function the time course of the present illness current medications

Premorbid cognitive function

can be assessed through the collateral source or, if needed, via a review of outpatient records

Delirium by definition

represents a change that is relatively acute, usually over hours to days, from a cognitive baseline.

As a result, an acute confusional state is nearly impossible to diagnose without some knowledge of baseline cognitive function.

Without this information, many patients with dementia or depression may be mistaken as delirious during a single initial evaluation.

Patients with a more hypoactive, apathetic presentation with psychomotor slowing may be identified as being different from baseline only through conversations with family members.



A number of validated instruments have been shown to diagnose cognitive dysfunction accurately by using a collateral source: o modified Blessed Dementia Rating

Scale o Clinical Dementia Rating (CDR).

Baseline cognitive impairment is common in patients with delirium.

Even when no such history of cognitive impairment is elicited, there should still be a high suspicion for a previously unrecognized underlying neurologic disorder

Time course of cognitive change

Establishing this is important not only to make a diagnosis of delirium but also to correlate the onset of the illness with potentially treatable etiologies such as recent medication changes or symptoms of systemic infection.

Medications remain a common cause of delirium, especially compounds with anticholinergic or sedative properties

1/3 of all cases of delirium are secondary to medications, especially in the elderly.

Medication histories should include o all prescription as well as over-the-

counter o herbal substances taken by the patient o any recent changes in dosing or

formulation o substitution of generics for brand-name

medications. Other important elements of the history

screening for symptoms of organ failure or systemic infection, which often contributes to delirium in the elderly

common in younger delirious patients: o A history of illicit drug use o Alcoholism o toxin exposure

other symptoms that may accompany delirium, such as depression and hallucinations, may help identify potential therapeutic targets.

PHYSICAL EXAMINATION

General Careful screening for signs of infection o Fever o Tachypnea o pulmonary consolidation o heart murmur o stiff neck

fluid status should be assessed; both dehydration and fluid overload with resultant hypoxemia have been associated with delirium, and each is usually easily rectified

appearance of the skin can be helpful o jaundice in hepatic

encephalopathy o cyanosis in hypoxemia o needle tracks in patients using

intravenous drugs Neurologic requires a careful assessment of

mental status Patients with delirium often present

with a fluctuating course diagnosis can be missed when one

relies on a single time point of

evaluation Some but not all patients exhibit the

characteristic pattern of sundowning, a wors- ening of their condition in the evening.

In these cases, assessment only during morning rounds may be falsely reassuring.

Altered level of consciousness

ranging from hyperarousal to lethargy to coma is present in most patients with delirium

can be assessed easily at the bedside

Patients w/ normal level of consciousness

screen for an attentional deficit (classic neuropsychological hallmark of delirium)

Attention can be assessed while taking a history

from the patient Tangential speech

o fragmentary flow of ideas, or inability to follow complex commands often signifies an attentional problem

There are formal neuropsychological tests to assess attention, but a simple bedside test of digit span forward is quick and fairly sensitive.

In this task, patients are asked to repeat successively longer random strings of digits beginning with two digits in a row.

Average adults can repeat a string of five to seven digits before faltering; a digit span of four or less usually indicates an attentional deficit unless hearing or language barriers are present.

Forman neuropsychological testing

can be extraordinarily helpful in assessing a delirious patient

usually too cumbersome and time-consuming in the inpatient setting

Simple Mini Mental Status Examination (MMSE)

can provide some information regarding orientation, language, and visuospatial skills

performance of some tasks on the MMSE such as spelling world backward and serial subtraction of digits will be impaired by delirious patients attentional deficits alone and are therefore unreliable

New focal neurologic deficits

Focus of remainder of the screening neurologic examination

Focal strokes or mass lesions in isolation o rarely the cause of delirium, but

patients with underlying extensive cerebrovascular disease or neurodegenerative conditions may not be able to cognitively tolerate even relatively small new insults

Signs of neurodegenerative conditions

Screen for parkinsonism, which is seen not only in idiopathic Parkinsons disease but also in other dementing conditions such as Alzheimers



disease, dementia with Lewy bodies, and progressive supranuclear palsy.

Motor examination presence of multifocal myoclonus or asterixis is nonspecific but usually indicates a metabolic or toxic etiology of the delirium.

ETIOLOGY Etiologies Some can be easily discerned through a

careful history and physical examination others require confirmation with laboratory

studies, imaging, or other ancillary tests A large, diverse group of insults can lead

to delirium, and the cause in many patients is often multifactorial.

Prescribed, pver-the-counter, and herbal medications

common precipitants of delirium Drugs with anticholinergic properties,

narcotics, and benzodiazepines are especially common offenders, but nearly any compound can lead to cognitive dysfunction in a predisposed patient.

elderly patient with baseline dementia may become delirious upon exposure to a relatively low dose of a medication

less susceptible individuals may become delirious only with very high doses of the same medication

importance of correlating the timing of recent medication changes, including dose and formulation, with the onset of cognitive dysfunction

Illicit drugs and toxins

common causes of delirium, especially in younger patients

increase in delirious young persons presenting to acute care settings due to recent rise in availability of so-called club drugs, o methylenedioxymethamphetamine

(MDMA, ecstasy), o -hydroxybutyrate (GHB) o phencyclidine (PCP)-like agent

ketamine Many common prescription drugs such as

oral narcotics and benzodiazepines are often abused and readily available on the street.

Alcohol intoxication with high serum levels can cause confusion

withdrawal from alcohol o more commonly leads to a classic

hyperactive delirium Alcohol and benzodiazepine withdrawal

o should be considered in all cases of delirium

o patients who drink only a few servings of alcohol every day can experience relatively severe withdrawal symptoms upon hospitalization

Metabolic abnormalities

electrolyte disturbances of sodium, calcium, magnesium, or glucose o can cause delirium

mild derangements o can lead to substantial cognitive

disturbances in susceptible individuals

Other common metabolic etiologies:

o liver and renal failure o hypercarbia and hypoxemia o vitamin deficiencies of thiamine

and B12 o autoimmune disorders including

central nervous system (CNS) vasculitis

o endocrinopathies such as thyroid and adrenal disorders.

Systemic infections

often cause delirium, especially in the elderly

common scenario o involves the development of an

acute cognitive decline in the setting of a urinary tract infection in a patient with baseline dementia.

Pneumonia, skin infections such as cellulitis, and frank sepsis also can lead to delirium.

septic encephalopathy o often seen in the ICU o probably due to the release of

proinflammatory cytokines and their diffuse cerebral effects.

CNS infections o such as meningitis, encephalitis,

and abscess o less common etiologies of delirium o high mortality rates associated with

these conditions when they are not treated quickly,

o clinicians must always maintain a high index of suspicion.

Exposure to unfamiliar environment of a hospital

In some susceptible individuals, this can lead to delirium.

usually occurs as part of a multifactorial delirium

should be considered a diagnosis of exclusion after all other causes have been thoroughly investigated

Many primary prevention and treatment strategies for delirium involve relatively simple methods to address the aspects of the inpatient setting that are most confusing.

Cerebrovascular etiologies

usually due to global hypoperfusion in the setting of systemic hypotension from heart failure, septic shock, dehydration, or anemia.

Focal strokes in the right parietal lobe and medial dorsal thalamus o rarely can lead to a delirious state

new focal stroke or hemorrhage o more common scenario causring

confusion in a patient who has decreased cerebral reserve

o sometimes difficult to distinguish between cognitive dysfunction resulting from the new neurovascular insult itself and delirium due to the infectious, metabolic, and pharmacologic complications that can accompany hospitalization after stroke.

Seizures intermittent seizures o may be overlooked when one is

considering potential etiologies,



because a fluctuating course often is seen in delirium

nonconvulsive status epilepticus and recurrent focal or generalized seizures followed by postictal confusion o can cause delirium o EEG remains essential for this

diagnosis. Seizure activity spreading from an

electrical focus in a mass or infarct can explain global cognitive dysfunction caused by relatively small lesions.

Terminal restlessness

patients experience delirium at the end of life in palliative care settings

must be identified and treated aggressively

an important cause of patient and family discomfort at the end of life

It should be remembered that these patients also may be suffering from more common etiologies of delirium such as systemic infection.

LABORATORY AND DIAGNOSTIC EVALUATION Cost-effective

approach to the diagnostic evaluation of delirium that allows the history and physical examination to guide tests

No established algorithm for workup will fit all delirious patients due to the staggering number of potential etiologies o one stepwise approach is detailed in

Table 25-2. If a clear precipitant is identiied early

o such as an offending medication o little further workup is required

If no likely etiology is uncovered with initial evaluation o an aggressive search for an underlying

cause should be initiated Basic screening labs

Should be obtained in all patients w/ delirium: o complete blood count o electrolyte panel o tests of liver and renal function

In elderly patients o screening for systemic infection is

important o chest radiography o urinalysis and culture o possibly blood cultures

In younger individuals o serum and urine drug and toxicology

screening may be appropriate early in the workup.

patients in whom the diagnosis remains unclear after initial testing

o Additional laboratory tests addressing other autoimmune, endocrinologic, metabolic, and infectious etiologies should be reserved.

Brain imaging

often unhelpful if the initial workup is unrevealing

o most clinicians quickly move toward imaging of the brain to exclude structural causes.

noncontrast CT scan o can identify large masses and

hemorrhages o relatively insensitive for discovering an

etiology of delirium MRI Able to identify most acute ischemic strokes provides neuroanatomic detail that gives clues to

possible infectious, inflammatory, neurodegenerative, and neoplastic conditions

test of choice MRI techniques are limited by:

o availability o speed of imaging o patient cooperation o contraindications to magnetic exposure

Many clinicians begin with CT scanning and proceed to MRI if the etiology of delirium remains elusive

Lumbar puncture (LP)

must be obtained immediately after appropriate neuroimaging in all patients in whom CNS infection is suspected.

Spinal fluid examination o can also be useful in identifying

inflammatory and neoplastic conditions and

o diagnosis of hepatic encephalopathy



through elevated cerebrospinal fluid (CSF) glutamine levels.

LP should be considered in any delirious patient with a negative workup.

EEG does not have a routine role in the workup of delirium

remains invaluable if seizure-related etiologies are considered

TREATMENT: DELIRIUM Management of delirium

begins with treatment of the underlying inciting factor o patients with systemic infections should

be given appropriate antibiotics o underlying electrolyte disturbances

judiciously corrected These treatments often lead to prompt

resolution of delirium. Blindly targeting the symptoms of delirium

pharmacologically o only serves to prolong the time patients

remain in the confused state o may mask important diagnostic

information medications used to boost cholinergic

tone in delirious patients o led to mixed results o not currently recommended

Simple methods of supportive care

can be highly effective in treating patients with delirium

Can reduce confusion: o Reorientation by the nursing staff and

family o visible clocks and calendars o outside-facing windows

Sensory isolation o should be prevented by providing

glasses and hearing aids to patients who need them

Sundowning o can be addressed to a large extent

through vigilance to appropriate sleep-wake cycles.

During the day o a well-lit room should be accompanied

by activities or exercises to prevent napping.

At night o a quiet, dark environment o limited interruptions by staff o assure proper rest

sleep-wake cycle interventions o important in the ICU setting as the

usual constant 24-h activity commonly provokes delirium

Attempting to mimic the home environment as much as possible o has been shown to help treat and even

prevent delirium. Visits from friends and family throughout

the day o minimize the anxiety associated with

the constant flow of new faces of staff and physicians.

Allowing hospitalized patients to have access to home bedding, clothing, and nightstand objects o makes the hospital environment less

foreign and therefore less confusing. Simple standard nursing practices:

o Ex. maintaining proper nutrition and volume status

o Ex. managing incontinence and skin breakdown

o help alleviate discomfort and resulting confusion

Acute management

required in some instances where patients pose a threat to their own safety or to the safety of staff members

Bed alarms and personal sitters vs physical restraints o more effective o much less disorienting

Chemical restraints o should be avoided o when necessary, very low dose typical

or atypical antipsychotic medications administered on an as-needed basis are effective.

association of antipsychotic use in the elderly with increased mortality rates o underscores the importance of using

these medications judiciously and only as a last resort

Benzodiazepines



o not as effective as antipsychotics o often worsen confusion through their

sedative properties. o Still used by many clinicians to treat

acute confusion o use should be limited to cases in which

delirium is caused by alcohol or benzodiazepine withdrawal

PREVENTION

It is extremely important to develop effective strategy to prevent delirium in hospitalizations, because of: o high morbidity associated with delirium o tremendously increased health care costs that

accompany it First step:

o Successful identification of high-risk patients followed by:

o initiation of appropriate interventions One trial randomized more than 850 elderly inpatients to

simple standardized protocols used to manage risk factors for delirium, including cognitive impairment, immobility, visual impairment, hearing impairment, sleep deprivation, and dehydration.

Significant reductions in the number and duration of episodes of delirium were observed in the treatment group, but unfortunately, delirium recurrence rates were unchanged.

Recent trials in the ICU have focused on identifying sedatives, such as dexmedetomidine, that are less likely to lead to delirium in critically ill patients.

All hospitals and health care systems should work toward developing standardized protocols to address common risk factors with the goal of decreasing the incidence of delirium.

medicine 4.7 - confusion and delirium

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