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Offi cial reprint from UpToDatewww.uptodate.com 2016 UpToDate

AuthorsJoseph Francis, Jr, MD, MPHG Bryan Young, MD, FRCPC

Section EditorsMichael J Aminoff, MD, DScKenneth E Schmader, MD

Deputy EditorJanet L Wilterdink, MD

Diagnosis of delirium and confusional states

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jan 2016. | This topic last updated:Aug 22, 2014.

INTRODUCTION Delirium and confusional states are among the most common mental disorders encountered

in patients with medical illness, particularly among those who are older. They are associated with many complex

underlying medical conditions and can be hard to recognize. Systematic studies and clinical trials are difficult to

perform in patients with cognitive impairment. Recommendations for evaluating and treating delirium are based

primarily upon clinical observation and expert opinion [1].

Knowledge of the clinical epidemiology of delirium and confusional states in various settings has substantially

increased as a result of applying standardized diagnostic methods. These prospective observational studies

provide a basis for understanding and managing the disorder.

The epidemiology, pathogenesis, clinical features, and diagnosis of delirium and confusional states will be

reviewed here. The prevention and treatment of these disorders are discussed separately. (See "Delirium and

acute confusional states: Prevention, treatment, and prognosis".)

DEFINITION AND TERMINOLOGY The American Psychiatric Association's Diagnostic and Statistical

Manual, 5th edition (DSM-V) lists five key features that characterize delirium [2]:

Additional features that may accompany delirium and confusion include the following:

There is no generally accepted consensus regarding the distinction between delirium and confusional states. The

terms "acute confusional state" and "encephalopathy" are often used synonymously with delirium. The more

general term "confusion" is used to indicate a problem with coherent thinking. Confused patients are unable to

think with normal speed, clarity, or coherence [3]. Confusion is typically associated with a depressed sensorium

and a reduced attention span, and it is an essential component of delirium.

The term "acute confusional state" refers to an acute state of altered consciousness characterized by disordered

attention along with diminished speed, clarity, and coherence of thought [ 3]. Although this definition encompasses

Disturbance in attention (reduced ability to direct, focus, sustain, and shift attention) and awareness.

The disturbance develops over a short period of time (usually hours to days), represents a change from

baseline, and tends to fluctuate during the course of the day.

An additional disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, or

perception)

The disturbances are not better explained by another preexisting, evolving or established neurocognitive

disorder, and do not occur in the context of a severely reduced level of arousal, such as coma

There is evidence from the history, physical examination, or laboratory findings that the disturbance is

caused by a medical condition, substance intoxication or withdrawal, or medication side effect.

Psychomotor behavioral disturbances such as hypoactivity, hyperactivity with increased sympathetic

activity, and impairment in sleep duration and architecture.

Variable emotional disturbances, including fear, depression, euphoria, or perplexity.
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delirium as well, some experts use "confusional state" to convey the additional meaning of reduced alertness and

altered psychomotor activity [3]. In this paradigm, delirium is a special type of confusional state characterized by

increased vigilance, with psychomotor and autonomic overactivity the delirious patient displays agitation,

excitement, tremulousness, hallucinations, fantasies, and delusions.

In this discussion, the term delirium will be used in the sense of the DSM-V definition. The additional components

of agitation, tremor, and hallucinations are allowed for but are not essential diagnostic features of delirium in the

DSM-V usage. Confusion and other states of altered consciousness are encompassed by the DSM-V definition of

delirium.

EPIDEMIOLOGY Delirium and confusion have primarily been studied in hospital settings. Nearly 30 percent of

older medical patients experience delirium at some time during hospitalization [ 4,5]. Among older surgical patients,

the risk for delirium varies from 10 to greater than 50 percent the higher figures are associated either with frail

patients (eg, those who have fallen and sustained a hip fracture) or complex procedures such as cardiac surgery

[6].

In general, delirium can be found wherever there are sick patients. When standardized screening and diagnostic

tools (see 'Evaluation'below) have been applied prospectively to consecutive patients, high rates of delirium have

been demonstrated in intensive care units (70 percent) [7], emergency departments (10 percent) [8], hospice units

(42 percent) [9], and postacute care settings (16 percent) [10]. Now that the care of sicker patients has become

fragmented across a variety of venues, clinicians are challenged to identify and manage delirium efficiently acrossa wide variety of settings.

PATHOGENESIS The pathophysiology of delirium and confusion is poorly understood. Most theories are overly

simplified. With so many disparate etiologies (table 1), it is highly unlikely that a single mechanism is universally

operative.

The biologic basis of delirium and confusion is poorly understood in part because it is difficult to study severely ill

patients with conventional electrophysiologic tests, brain imaging, or neurotransmitter assays. Rarely can the

observed phenomena attributed to delirium be separated reliably from that of underlying illness and drug treatment.

Animal models for delirium have been proposed but are in their infancy and still not validated.

Despite these limitations, some important data regarding the pathophysiology of delirium have been reported. Riskfactors for the development of delirium have also been identified.

Neurobiology of attention Since a disorder of attention is a universal feature of confusional states, it helps to

understand the neurobiology of attention.

Cortical versus subcortical mechanisms Seminal work in the 1940s using electroencephalography (EEG) in

acutely ill patients established that delirium was a disturbance of global cortical function, characterized by slowing

of the dominant posterior alpha rhythm and the appearance of abnormal slow-wave activity [ 11]. These findings

correlated with the level of consciousness and other observed behaviors regardless of the underlying etiology,

suggesting a final common neural pathway. The major exception appeared to be that of delirium accompanying

Arousal and attention may be disrupted by brain lesions involving the ascending reticular activating system

(ARAS) from the mid-pontine tegmentum rostrally to the anterior cingulate regions.

Attention in both right and left aspects of extrapersonal space is governed by the "nondominant" parietal and

frontal lobes. Thus with inattention, there is typically some disruption of the integrated function of these

regions.

Insight and judgment are dependent on intact higher order integrated cortical function. Since insight into

perceptions is often reduced with delirium and confusional states, it seems likely that higher order cortical

function is therefore impaired, especially regarding frontal lobe involvement in scrutinizing incoming sensory

information.
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alcohol and sedative drug withdrawal, in which low voltage, fast-wave activity predominated. These findings are so

consistent that EEG can be used to resolve uncertainty in patients in whom the diagnosis of delirium is in doubt.

The results of brainstem auditory evoked potential, somatosensory evoked potentials, and neuroimaging studies

have supported an important role for subcortical (eg, thalamus, basal ganglia, and pontine reticular formation) as

well as cortical structures in the pathogenesis of delirium [12]. These findings correlate with clinical reports that

patients with subcortical strokes and basal ganglia abnormalities (including Parkinson disease) have a higher

susceptibility to delirium.

Neurotransmitter and humoral mechanisms Acetylcholine plays a key role in the pathogenesis of delirium[13,14]. Anticholinergic drugs cause delirium when given to healthy volunteers and are even more likely to lead to

acute confusion in frail elderly persons. This effect can be reversed with cholinesterase inhibitors such as

physostigmine. (See "Anticholinergic poisoning".)

Further support for the role of acetylcholine is derived from observations that medical conditions precipitating

delirium, such as hypoxia, hypoglycemia, and thiamine deficiency, decrease acetylcholine synthesis in the central

nervous system (CNS). In addition, serum anticholinergic activity, measured with binding assays employing

purified preparations of brain muscarinic receptors, correlates with the severity of delirium in postoperative and

medical patients [13,15]. Finally, Alzheimer disease, which is characterized by a loss of cholinergic neurons,

increases the risk of delirium due to anticholinergic medications.

The anticholinergic mechanism is important for clinicians to keep in mind, since many drugs used by older adults

(including several not traditionally viewed to have "anticholinergic effects") can lead to detectable serum

anticholinergic activity measured by competitive radioreceptor binding [16,17]. Psychotropic drugs, in particular,

are likely to cause detectable serum anticholinergic activity at doses typically administered to older patients. Some

elderly patients with delirium also have elevated serum anticholinergic activity in the absence of anticholinergic

drug use, raising the possibility that endogenous anticholinergic substances may play a role in delirium [ 13].

Drugs that are agonists or antagonists of a number of other neurotransmitters can produce delirium-like effects,

although the precise role of these neurotransmitter systems is difficult to determine. Cerebrospinal fluid (CSF)

studies of patients with delirium reveal alterations in neuropeptides (eg, somatostatin), endorphins, serotonin,

norepinephrine, and GABA, among others [12]. However, it is difficult to exclude the confounding effects of

underlying illness or dementia.

Pro-inflammatory cytokines such as interleukins and tumor necrosis factor alpha also may have a role in the

pathogenesis of delirium. These agents have strong CNS effects when injected into experimental animals or when

administered for therapeutic purposes (eg, interferons in chronic hepatitis). Cytokine activation may account for

delirium (particularly hyperactive forms of the disturbance) in situations such as sepsis (where mental changes

may actually precede fever), cardiopulmonary bypass [18], and acute hip fracture [19].

Risk factors Delirium is a multifactorial disorder. Factors that increase the risk for delirium and confusional

states can be classified into those that increase baseline vulnerability and those that precipitate the disturbance

[20].

The most commonly identified risk factors are underlying brain diseases such as dementia, stroke, or Parkinson

disease these are present in nearly one-half of older patients with delirium. In a meta-analysis of published

prospective studies of delirium, the prevalence of delirium superimposed upon dementia ranged from 22 to 89

percent [21]. Often, the dementia went unrecognized prior to the onset of delirium. Similarly, in a study of 78

elderly patients with femoral neck fractures who were followed for five years, dementia developed in 69 percent of

the 29 patients with postoperative delirium versus only 20 percent of the 49 patients without postoperative delirium

[22].

Other factors that increase the vulnerability to delirium include advanced age and sensory impairment.

Precipitating factors Factors that may precipitate delirium are numerous and varied (table 1). Some common
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examples include polypharmacy (particularly psychoactive drugs), infection, dehydration, immobility (including

restraint use), malnutrition, and the use of bladder catheters. Drugs that may precipitate delirium and confusion are

noted in the Table (table 2).

CLINICAL PRESENTATION As previously noted, several key features characterize delirium and confusional

states (see 'Definition and terminology' above) [2]. A disturbance of consciousness and altered cognition are

essential components. The condition typically develops over a short period of time and tends to fluctuate during

the course of the day. The disturbance is typically caused by a medical condition, substance intoxication, or

medication side effect. These criteria form a useful framework for understanding the clinical presentation of the

disorder.

Disturbance of consciousness One of the earliest manifestations of delirium is a change in the level of

awareness and the ability to focus, sustain, or shift attention. This loss of mental clarity is often subtle and may

precede more flagrant signs of delirium by one day or more. Thus, family members or caregivers who report that a

patient "isn't acting quite right" should be taken seriously, even if delirium is not obvious to the examining clinician.

Distractibility, one of the hallmarks of delirium, is often evident in conversation. It is important that the examiner be

sensitive to the patient's flow of thought and not attribute tangential or disorganized speech to age, dementia, or

fatigue.

Patients will appear obviously drowsy, lethargic, or even semi-comatose in more advanced cases of delirium. The

opposite extreme, hypervigilance, may also occur in cases of alcohol or sedative drug withdrawal, but such a

presentation is less common in older persons. (See "Management of moderate and severe alcohol withdrawal

syndromes".)

Change in cognition Delirious individuals have cognitive and perceptual problems, including memory loss,

disorientation, and difficulty with language and speech. Formal mental status testing can be used to document the

degree of impairment, but more important than the test score are the patient's overall accessibility and

attentiveness while attempting to answer the questions. It is important to ascertain the patient's level of

functioning prior to the onset of delirium from family members, caregivers, or other reliable informants, since

dementia can impair cognitive ability and frequently underlies delirium.

Perceptual disturbances typically accompany delirium. Patients may misidentify the clinician or believe thatobjects or shadows in the room represent a person. Vague delusions of harm often accompany these

misperceptions. Hallucinations can be visual, auditory or somatosensory, usually with lack of insight - the patients

believe they are real. Hallucinations can be simple, e.g., shadows or shapes, or complex, as people and faces.

Sounds can also consist of simple sounds or hearing voices with clear speech.

A variety of language difficulties can occur. Patients may lose the ability to write or to speak a second language.

One personal experience involved a patient who immigrated to North America as an adolescent she spoke only

Italian during her delirium, recovering her grasp of English after her pneumonia was treated.

Temporal course Delirium develops over hours to days and typically persists for days to months. The

acuteness of the presentation is the most helpful feature in differentiating delirium from dementia. In addition, the

features of delirium are unstable, typically becoming most severe in the evening and at night. It is not unusual for a

patient with delirium to appear relatively lucid during morning rounds. Clinicians, particularly physicians, are apt to

miss the diagnosis if they rely upon only a single point assessment evidence of the behavior change should be

actively solicited from all staff, especially those working evening and night shifts.

There is often a prodromal phase, especially in elderly patients, that later blends into quiet/hypoactive delirium or

erupts into an agitated confusional state. Prodromal features include complaints of fatigue, sleep disturbance

(excessive daytime somnolence or insomnia), depression, anxiety, restlessness, irritability and hypersensitivity to

light or sound. With progression there are perceptual disturbances and cognitive impairment. These symptoms

may fluctuate. Hypoactive delirium can, however, begin without a prodromal phase and agitated behavior may
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appear as the first manifestation of delirium without a prodromal or hypoactive phase.

Elderly patients Patients with delirium are sick by definition. However, older patients with delirium often do not

look sick apart from their behavioral change. Thus, delirium may be the only finding suggesting acute illness in

older demented patients. Caregivers must be educated that sudden changes in mental functioning are not

expected with most progressive dementias and require prompt medical attention.

Other features Delirium may present with a variety of clinical manifestations that are not essential diagnostic

features, including psychomotor agitation, sleep-wake reversals, irritability, anxiety, emotional lability, and

hypersensitivity to lights and sounds. These features are not seen in all patients with delirium and can be evidentin patients with dementia their presence neither rules in nor rules out the diagnosis. The most common

presentation in older patients is a relatively quiet, withdrawn state that frequently is mistaken for depression.

The relationship between clinical manifestations and outcome has not been well studied, although a report of

outcomes of delirium following hip fracture repair suggested that patients with more severe delirium, including

psychomotor agitation, had higher rates of mortality and nursing home placement [23]. Delirium that does not

resolve before discharge is also a risk factor for nursing home placement [24].

EVALUATION There are two important aspects to the diagnostic evaluation of delirium: recognizing that the

disorder is present and uncovering the underlying medical illness that has caused delirium.

Recognizing the disorder As previously mentioned, clinicians often fail to recognize delirium in some reports,this happens in more than 70 percent of cases. Behavioral problems or cognitive impairment may be readily

apparent but wrongly attributed to the patient's age, to dementia, or to other mental disorders. In one study, over

40 percent of patients referred to a consulting liaison psychiatrist for the evaluation or treatment of depression

ultimately were found to have delirium [23].

Clinical confirmation The DSM-V criteria (See 'Definition and terminology' above.) form a practical framework

for assessing delirium [25]:

Determining that cognitive impairment or perceptual problems are not due to a prior or progressing dementia can be

challenging and requires knowledge of the patient's baseline level of functioning. The diagnosis is made more

easily if there has been a prior assessment of cognitive abilities. In other instances, informants must be

immediately sought to establish chronology. These should include formal caregivers (eg, nursing staff familiar with

the patient), family members, and informal caregivers, particularly those who may have observed fluctuations in

the patient's mental functions.

History Some historical clues to the underlying etiology of delirium and confusion can be obtained from

relatives, eg, recent febrile illness, history of organ failure, a medication list, history of alcoholism or drug abuse, or

recent depression. It is otherwise often difficult to impossible to obtain a history in the confused or uncooperative

A change in the level of consciousness is often the first observable clue. Clinicians must not "normalize"

lethargy or somnolence by assuming that illness, sleep loss, fatigue, or anxiety are causing the changes.

In cases where the patient appears awake, the ability to focus, sustain, or shift attention can be assessedduring attempts to obtain a history a global assessment of the patient's "accessibility" during conversation or

the performance of a mental status examination is a sensitive indicator of delirium.

Conversation with the patient may elicit memory difficulties, disorientation, or speech that is tangential,

disorganized, or incoherent. The clinician should be aware of superficially appropriate conversation that

follows social norms but is poor in content.

When in doubt, formal mental status testing should be performed, such as the Mini-Mental State Examination

or brief bedside tests of attention (table 3). Serial-sevens and spelling a word such as farm or world

backward are other simple tests of attention. (See "Evaluation of cognitive impairment and dementia",

section on 'Mini-Mental State Examination'.)
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patient. As an example, myocardial infarction may cause sufficient confusion that the patient cannot relate a

history of chest pain.

General examination A comprehensive physical examination is often difficult or impossible in the confused

or uncooperative patient. Clinicians should instead perform a focused assessment, concentrating upon vital signs,

the state of hydration, skin condition, and potential infectious foci.

The patient's general appearance may be suggestive, eg, the dusky appearance seen with chronic pulmonary

disease, the jaundiced appearance of hepatic failure, or the stigmata of renal failure. Needle tracks strongly

suggest drug abuse. Cherry-red lips indicate possible carbon monoxide poisoning. The breath may smell ofalcohol, fetor hepaticus, uremic fetor or ketones. Hyperventilation offers a limited number of possible etiologies.

(See 'Diagnostic tests' below.)

A bitten tongue or posterior fracture-dislocation of the shoulder suggests a convulsive seizure (over 40 percent of

such patients remain in nonconvulsive status epilepticus). There may also be signs of head injury. Subhyaloid or

retinal hemorrhages raise the possibility of an intracranial hemorrhage, usually from a ruptured berry aneurysm.

Alcohol or sedative-drug withdrawal may cause a delirium characterized by autonomic nervous system activation

(tachycardia, sweating, flushing, dilated pupils) in younger persons, but these responses are blunted or absent in

the geriatric population. Anticholinergic toxicity in elders can cause delirium without peripheral signs of atropine

poisoning (eg, fever, mydriasis, tachycardia). Sepsis may present as delirium without obvious fever (sometimes

even with hypothermia) or localizing signs (eg, rebound tenderness from a perforated viscus). (See "Evaluation of

infection in the older adult".)

Pitfalls in the examination must be kept in mind: temperature may be under 38.3C (101F) even in the presence of

serious infections auscultatory and radiographic findings of pneumonia may be subtle or absent and abdominal

catastrophes may present without peritoneal signs in frail older patients. False-positive findings occur as well (eg,

nuchal rigidity may not signify meningitis).

Neurologic examination The neurologic examination is often confounded by inattention and altered

consciousness in patients with delirium. Certain aspects of the examination may be difficult or unreliable in

uncooperative patients (eg, sensory testing), or reflect chronic rather than acute CNS conditions. However, an

assessment emphasizing the level of consciousness, degree of attention or inattention, visual fields, andunambiguous cranial nerve and motor deficits, is important to identify individuals with a higher likelihood of focal

neurologic disease. Posterior cortical strokes, for example, can present as delirium with few findings other than

hemianopia, and in some cases may present with no focal symptoms or signs.

The absence of focal examination findings does not exclude the possibility of focal or multifocal neurologic lesions

as the cause of the delirium. In the absence of an obvious cause for delirium, further testing including

neuroimaging, lumbar puncture, and EEG is indicated.

The physical signs of metabolic/toxic delirium can include nonrhythmic, asynchronous muscle jerking (multifocal

myoclonus), flapping motions of an outstretched, dorsiflexed hand (asterixis), and postural action tremor. These

are nonspecific findings and do not help establish any particular medical etiology within the metabolic/toxic

category. Selective loss of the vestibular-ocular reflex, or nystagmus with unexplained ocular palsies that spare

pupillary reactivity to light, raise the possibility of Wernicke's encephalopathy.

Clinical instruments The Confusion Assessment Method (CAM) is a simple tool that can be used by

clinicians to integrate their observations and identify when delirium is the most probable diagnosis ( table 4). In

medical and surgical settings, the CAM has a sensitivity of 94 to 100 percent and a specificity of 90 to 95 percent

[26]. The CAM has become a standard screening device in clinical studies of delirium, conducted across multiple

settings including emergency rooms and long-term care [27]. It takes five minutes to administer and may be

particularly helpful when incorporated into the routine bedside assessment. A review of 11 bedside instruments

used to identify the presence of delirium in adults concluded that the best evidence supported the use of the CAM
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as the best, and the Mini Mental State Exam as the least accurate test [ 28].

The CAM-ICU instrument has been developed and validated for identification of delirium in the intensive care unit

(ICU) [29-31]. In mechanically ventilated patients who are unable to communicate verbally, the instrument

considers observed behaviors and nonverbal responses to simple questions, as well as visual and auditory

recognition tasks (table 4).

Another instrument, the Intensive Care Delirium Checklist for Screening (ICDSC), has also been validated in the

diagnosis of delirium in the ICU setting and had high agreement rates with the CAM-ICU in one study [ 32,33].

Investigating medical etiologies Virtually any medical condition can precipitate delirium in a susceptible

person multiple underlying conditions are often found [34]. The history and physical examination will guide most of

the investigations. The conditions noted most commonly in prospective studies of the disorder include:

Less common causes that should be considered include hypoxemia, hypercarbia, Wernicke encephalopathy,

adrenal failure, primary central nervous system infection, seizures, trauma, and paraneoplastic syndromes.

A cost-effective work-up for delirium focuses upon these most likely possibilities. (See "Delirium and acute

confusional states: Prevention, treatment, and prognosis".)

Medication review Drug toxicity accounts for approximately 30 percent of all cases of delirium [16]. Thus, the

most important initial step is a medication review. The most common offenders are listed in the Table (table 2)

[16]. Clinicians should be careful not to neglect over-the-counter agents, drugs prescribed by other physicians, or

drugs belonging to other household members. A simple but high-yield diagnostic procedure is to ask a family

member to clean out the medicine cabinet and bring the contents for review.

DIFFERENTIAL DIAGNOSIS Careful attention to the key features of acute onset, fluctuating course, altered

consciousness, and cognitive decline should readily distinguish delirium from depression, psychotic illness, and

dementia. When in doubt, the most useful rule-of-thumb is to assume delirium and attempt to rule out common

medical etiologies. This is true even for patients with known psychiatric illness (including dementia), since they

also are susceptible to delirium when acutely ill.

Sundowning Delirium should be distinguished from "sundowning," a frequently seen but poorly understood

phenomenon of behavioral deterioration seen in the evening hours, typically in demented, institutionalized patients

[35]. Sundowning should be presumed to be delirium when it is a new pattern. Patients with establishedsundowning and no obvious medical illness may be suffering the effects of impaired circadian regulation or

nocturnal factors in the institutional environment (eg, shift changes, noise, reduced staffing).

Focal syndromes A number of lobar or focal neurologic syndromes may mimic delirium.

Fluid and electrolyte disturbances (dehydration, hyponatremia and hypernatremia)

Infections (urinary tract, respiratory tract, skin and soft tissue)

Drug or alcohol toxicity

Withdrawal from alcohol

Withdrawal from barbiturates, benzodiazepines, and selective serotonin reuptake inhibitors

Metabolic disorders (hypoglycemia, hypercalcemia, uremia, liver failure, thyrotoxicosis)

Low perfusion states (shock, heart failure)

Postoperative states, especially in the elderly

Temporal-parietal Patients with Wernicke's aphasia may appear delirious in that they do not comprehend

or obey and seem confused. However, the problem is restricted to language, while other aspects of mental

function are intact. Furthermore, fluent paraphasias are typically present with Wernicke's and offer a major

clue to the correct diagnosis.

Bitemporal dysfunction, if transient, may produce a transient global amnesia (TGA), in which the deficit is
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Confusion or delirium due to acute or subacute brain lesions, such as stroke or multifocal white matter

inflammation, may occur without focal deficits on examination [ 36-39]. One retrospective study of 127 consecutive

neurology consultations for isolated acute mental status change found stroke as the cause in nine patients (7

percent) [37]. Of these, three patients (2.7 percent) with stroke had no focal neurologic findings, and one of these

was a subarachnoid hemorrhage. Risk factors for delirium in the setting of stroke include pre-existing cognitive

impairment, infection, right hemispheric stroke, anterior circulation large vessel stroke, and greater stroke severity

[39].

Confusion or delirium may follow head injury even in the absence of focal neurologic deficits.

Nonconvulsive status epilepticus Nonconvulsive status epilepticus (NCSE) is under-recognized, particularly

in older patients. NCSE requires an EEG for detection and continuous EEG for management. Often patients show

no classic ictal features, but the following features should suggest the possibility of seizures: prominent bilateral

facial twitching, unexplained nystagmoid eye movements during obtunded periods, spontaneous hippus, prolonged

"post-ictal state," automatisms (lip smacking, chewing, or swallowing movements), and acute aphasia or neglect

without a structural lesion [40]. NCSE should also be considered in the absence of these findings when the

etiology of a confusional state remains obscure [41].

Dementia Dementia may sometimes be confused with delirium or confusion and vice-versa. However,

characteristic differences in progression and cognitive features usually distinguish these disorders.

Primary psychiatric illnesses Delirium is commonly misdiagnosed as depression. Both are associated with

poor sleep and difficulty with attention or concentration. Agitated depression may be especially problematic.

However, depression is associated with dysphoria, and there is less fluctuation than in delirium.

Mania can be confused with hyperactive delirium with agitation, delusions, and psychotic behavior. However,

mania is usually associated with a history of previous episodes of mania or depression. In schizophrenia, the

delusions are usually highly systematized, the history is longer, and the sensorium is otherwise clear.

DIAGNOSTIC TESTS

Laboratory tests A number of laboratory tests may be considered in the patient with delirium. However, the

desire for diagnostic completeness can increase costs and possibly delay the prompt treatment of more obvious

disorders. Targeted testing is appropriate in most instances.

restricted to memory. With more extensive bitemporal dysfunction, visual agnosia and cortical deafness

(either bitemporal or left temporal) or the Kluver-Bucy syndrome (apathy, visual agnosia, increased sexual

activity, and increased oral behavior) may be seen.

Occipital Anton's syndrome of cortical blindness and confabulation might be confused with delirium.

Careful examination, however, will reveal a lack of vision.

Frontal Patients with bifrontal lesions (eg, from tumor or trauma) often show akinetic mutism, lack of

spontaneity, lack of judgment, problems with recent or working memory, blunted or labile emotional

responses, and incontinence. These features may closely resemble delirium. Neuroimaging may be requiredto differentiate frontal lesions from delirium and confusional states in difficult cases.

In contrast to delirium, cognitive change in Alzheimer disease is typically insidious, progressive, without

much fluctuation, and occurs over a much longer time (months to years). Attention is relatively intact, as are

remote memories in the earlier stages. (See "Clinical features and diagnosis of Alzheimer disease", section

on 'Clinical features'.)

Dementia with Lewy bodies (DLB) is similar to Alzheimer disease but can be more easily confused with

delirium, because fluctuations and visual hallucinations are common and prominent. (See "Clinical features

and diagnosis of dementia with Lewy bodies".)
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Neuroimaging Neuroimaging with head CT may be used selectively rather than routinely for most patients with

delirium. However, neuroimaging is necessary, if no obvious cause of delirium is apparent on first evaluation.

The need for imaging should be guided by patient history and findings on neurologic examination. Neuroimaging

may not be necessary if a patient with acute delirium meets the following conditions: the initial clinical evaluation

discloses an obvious treatable medical illness or problem, there is no evidence of trauma, no new focal neurologic

signs are present, and the patient is arousable and able to follow simple commands. However, neuroimaging

should be reconsidered if the patient doesn't improve as expected.

Neuroimaging may still be required if the delirium does not improve despite appropriate treatment of the underlying

medical problem. In addition, imaging should be considered if the neurologic examination is confounded by

diminished patient responsiveness or cooperation.

There have been no well-designed prospective studies to assess the yield of neuroimaging in patients withdelirium. Abnormalities on head CT are commonly seen, but they usually represent chronic conditions that

predispose to delirium rather than acute, treatable causes [42]. Examples of retrospective studies include:

Fewer data exist for MRI evaluation of patients with delirium. However, MRI is more sensitive than head CT for

acute stroke, posterior fossa lesions, and white matter lesions, however, such findings may not influence

immediate treatment course in critically ill patients [44]. In patients with delirium of unknown cause and negative

head CT, MRI may be useful to exclude acute or subacute stroke and multifocal inflammatory lesions (eg, as seen

in reversible posterior leukoencephalopathy and acute disseminated encephalomyelitis).

Serum electrolytes, creatinine, glucose, calcium, complete blood count, and urinalysis and urine culture are

reasonable for most patients when a cause is not immediately obvious.

Drug levels should be ordered where appropriate. However, clinicians must be aware that delirium can occur

even with "therapeutic" levels of such agents as digoxin, lithium, or quinidine.

Toxic screen of blood and urine should be obtained from patients with acute delirium or confusion when a

cause is not immediately obvious. Again, clinicians must be aware that some common drugs (eg,

risperidone) are not assessed in routine laboratory screens. Therefore, overdose of these drugs cannot be

excluded by negative results from a toxic screen.

Blood gas determination is often helpful. In hyperventilating patients, respiratory alkalosis is most commonly

due to early sepsis, hepatic failure, early salicylate intoxication, or cardiopulmonary causes. A metabolic

acidosis usually reflects uremia, diabetic ketoacidosis, lactic acidosis, late phases of sepsis or salicylate

intoxication, or toxins including methanol and ethylene glycol. A chest x-ray is usually performed.

Further testing, such as liver function tests, should be based upon the history and clinical examination. A

report of slow cognitive decline over several months, for example, will increase the importance of evaluating

thyroid function and vitamin B12 levels.

A retrospective study of 294 patients with acute confusion found revealed abnormal CTs in 14 percent overall

[43]. However, only 4 percent of patients without focal signs had abnormal CT the lowest yield of CT (2

percent) was in patients with premorbid dementia and no focal neurologic signs.

In a review of CT scans performed in 123 medical intensive care unit patients, new CT findings were present

in 26, leading to a change in diagnosis in 11 and a new treatment plan in 6 [ 36]. Most studies were performed

for an indication of "altered mental status" and findings included cerebral infarction in 13, intracranial

hemorrhage in 2, and tumor in 3.

In another review of 279 head CT scans performed in the emergency department in patients older than 70

years, 42 (15 percent) revealed an acute condition [38]. Of these, 40 were found in patients with either

significantly impaired consciousness (eg, unable to open eyes, speak, or follow simple commands) and/or

new focal neurologic findings.
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Lumbar puncture Older patients with bacterial meningitis are more likely to present with delirium rather than

the classic triad of fever, headache, and meningismus. Bacterial meningitis is an uncommon disorder, and routine

cerebrospinal fluid (CSF) evaluation may not be necessary in all febrile or septic appearing older patients with

delirium as long as other infectious foci are obvious. However, CSF analysis may be the only diagnostic tool that

will identify bacterial or aseptic meningitis and encephalitis.

In a retrospective study of 81 elderly patients who were admitted to the hospital for the evaluation of fever and

mental status changes, CSF cultures were negative for bacterial growth in 80 of 81 patients [ 45]. However, one

case of bacterial meningitis and one case of aseptic meningitis were diagnosed by CSF findings. In a

retrospective review of 232 lumbar punctures performed in hospitalized patients for the indication of altered mental

status, 11 percent were abnormal the yield was highest in those suspected of community-acquired meningitis

[46].

Lumbar puncture is mandatory when the cause of delirium is not obvious. Clinicians should also have a low

threshold for obtaining CSF in febrile patients with delirium, even when alternate explanatory conditions for delirium

are present or suspected.

Neuroimaging should be obtained prior to lumbar puncture in patients with coma, focal signs, papilledema, or

suspicion of increased intracranial pressure because of the very low but real risk of precipitating transtentorial

herniation. If lumbar puncture is delayed and the suspicion of bacterial meningitis is high, empiric antibiotic

treatment should be considered. (See "Lumbar puncture: Technique, indications, contraindications, andcomplications in adults", section on 'Complications' and "Clinical features and diagnosis of acute bacterial

meningitis in adults".)

EEG testing Electroencephalography (EEG) is useful in patients with altered consciousness in order to [47,48]:

Nonconvulsive seizures lack motor manifestations or convulsions, but they may impair consciousness.

Nonconvulsive status epilepticus may cause continuous or fluctuating impairment of consciousness, and EEG is

the only method that can make the diagnosis. One report evaluated 198 EEGs performed for the indication ofaltered consciousness without convulsions and found definite or probable nonconvulsive status epilepticus in 74

(37 percent) [49]. In another study, continuous EEG monitoring was performed for unexplained decrease in

consciousness or detection of subclinical seizures in 570 critically ill patients [50]. Seizures were detected in 110

patients (19 percent), and the seizures were exclusively nonconvulsive in 92 percent of these individuals. Coma

patients frequently required greater than 24 hours of monitoring to detect the first electrographic seizure.

Metabolic encephalopathies may show diffuse bilateral slowing of background rhythm and moderate or high wave

amplitude. Triphasic waves are associated with hepatic encephalopathy but can be seen in other severe metabolic

disturbances including uremic and septic encephalopathy [51,52]. Viral encephalitis is typically associated with

diffuse background slowing and occasional epileptiform activity or electrographic seizures. Herpes simplex

encephalitis may be associated with high amplitude periodic complexes in the temporal lobe leads.

EEG evaluation should be obtained for any patient with altered consciousness of unknown etiology [40]. Patients

with a remote or recent history of head trauma, stroke, seizures, or focal brain lesions may be at higher risk of

convulsive and nonconvulsive seizures. However, neither clinical signs nor prior history predicted which of the 198

EEGs showed nonconvulsive status in the study cited above [49].

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and

Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5 to 6 grade

reading level, and they answer the four or five key questions a patient might have about a given condition. These

articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond

Exclude seizures, especially nonconvulsive or subclinical seizures

Confirm the diagnosis of certain metabolic encephalopathies or infectious encephalitides that have

characteristic EEG patterns

th th
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the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written

at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable

with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these

topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on

patient info and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

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REFERENCES

1. Inouye SK. The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluationof delirium in hospitalized elderly medical patients. Am J Med 1994 97:278.

2. American Psychiatric Association, Diagnostic and Statistical Manual, 5th ed, APA Press, Washington, DC2013.

3. Adams RD, Victor M, Ropper AH. Delirium and other acute confusional states. In: Principles of Neurology,6th, McGraw-Hill, New York 1997. p.405.

4. Francis J. Delirium in older patients. J Am Geriatr Soc 1992 40:829.

5. Inouye SK, Rushing JT, Foreman MD, et al. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med 1998 13:234.

6. Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium. A review of 80 primary data-collection studies.

th th

Basics topic (see "Patient information: Delirium (confusion) (The Basics)")

Beyond the Basics topic (see "Patient information: Delirium (Beyond the Basics)")

Delirium is a clinical syndrome caused by a medical condition, substance intoxication or withdrawal, or

medication side effect that is characterized by a disturbance of consciousness with reduced ability to focus,

sustain, or shift attention (See 'Definition and terminology'above.)

Nearly 30 percent of older medical patients experience delirium at some time during hospitalization. The

incidence is higher in those with advanced age and pre-existing brain disease (See 'Epidemiology'above.)

A disturbance of consciousness and altered cognition are essential components of delirium. Some patients

are drowsy and lethargic, others are agitated and confused. Visual hallucinations, tremulousness, and

myoclonus/asterixis are variably present (See 'Clinical presentation' above and 'Neurologic examination'

above.).

Focal or lateralized neurologic findings are not characteristic of delirium. A careful neurologic

examination can also distinguish between focal syndromes that can mimic delirium (See 'Focal

syndromes'above.)

The past medical history, a review of medications, and a physical examination may provide clues as to the

underlying etiology (See 'History'above and 'General examination'above.)

Laboratory evaluation in patients with delirium should include serum electrolytes, creatinine, glucose,

calcium, complete blood count, and urinalysis and urine culture. Drug levels, toxicology screen, liver function

testing, and arterial blood gas should follow if the cause remains obscure (See 'Laboratory tests' above.).

Neuroimaging, lumbar puncture, and electroencephalogram are not required in most patients with delirium,

but are recommended in specific clinical scenarios, including in those whose cause remains obscure after

routine testing (See 'Diagnostic tests'above.)
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Arch Intern Med 1995 155:461.

7. McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course inolder patients. J Am Geriatr Soc 2003 51:591.

8. Elie M, Rousseau F, Cole M, et al. Prevalence and detection of delirium in elderly emergency departmentpatients. CMAJ 2000 163:977.

9. Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients withadvanced cancer: a prospective study. Arch Intern Med 2000 160:786.

10. Kiely DK, Bergmann MA, Murphy KM, et al. Delirium among newly admitted postacute facility patients:

prevalence, symptoms, and severity. J Gerontol A Biol Sci Med Sci 2003 58:M441.11. Romano J, Engel GL. Delirium: I. Electroencephalographic data. Arch Neurol Psychiatr 1944 51:356.

12. Trzepacz PT. The neuropathogenesis of delirium. A need to focus our research. Psychosomatics 199435:374.

13. Mach JR Jr, Dysken MW, Kuskowski M, et al. Serum anticholinergic activity in hospitalized older personswith delirium: a preliminary study. J Am Geriatr Soc 1995 43:491.

14. Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: a clinical review. ClinInterv Aging 2009 4:225.

15. Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium insurgical patients. Am J Psychiatry 1987 144:1218.

16. Francis J. Drug-induced delirium: Diagnosis and treatment. CNS Drugs 1996 5:103.

17. Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used byolder adults. J Am Geriatr Soc 2008 56:1333.

18. Stefano GB, Bilfinger TV, Fricchione GL. The immune-neuro-link and the macrophage: postcardiotomydelirium, HIV-associated dementia and psychiatry. Prog Neurobiol 1994 42:475.

19. van Munster BC, Korevaar JC, Zwinderman AH, et al. Time-course of cytokines during delirium in elderlypatients with hip fractures. J Am Geriatr Soc 2008 56:1704.

20. Elie M, Cole MG, Primeau FJ, Bellavance F. Delirium risk factors in elderly hospitalized patients. J GenIntern Med 1998 13:204.

21. Fick DM, Agostini JV, Inouye SK. Delirium superimposed on dementia: a systematic review. J Am GeriatrSoc 2002 50:1723.

22. Lundstrm M, Edlund A, Bucht G, et al. Dementia after delirium in patients with femoral neck fractures. JAm Geriatr Soc 2003 51:1002.

23. Marcantonio E, Ta T, Duthie E, Resnick NM. Delirium severity and psychomotor types: their relationshipwith outcomes after hip fracture repair. J Am Geriatr Soc 2002 50:850.

24. McAvay GJ, Van Ness PH, Bogardus ST Jr, et al. Older adults discharged from the hospital with delirium:1-year outcomes. J Am Geriatr Soc 2006 54:1245.

25. Pompei P, Foreman M, Cassel CK, et al. Detecting delirium among hospitalized older patients. Arch InternMed 1995 155:301.

26. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A newmethod for detection of delirium. Ann Intern Med 1990 113:941.

27. Wei LA, Fearing MA, Sternberg EJ, Inouye SK. The Confusion Assessment Method: a systematic review ofcurrent usage. J Am Geriatr Soc 2008 56:823.

28. Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium?: value of bedsideinstruments. JAMA 2010 304:779.

29. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability ofthe confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001 286:2703.

30. Luetz A, Heymann A, Radtke FM, et al. Different assessment tools for intensive care unit delirium: whichscore to use? Crit Care Med 2010 38:409.

31. Mitasova A, Kostalova M, Bednarik J, et al. Poststroke delirium incidence and outcomes: validation of theConfusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2012 40:484.

32. Plaschke K, von Haken R, Scholz M, et al. Comparison of the confusion assessment method for the
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intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium incritical care patients gives high agreement rate(s). Intensive Care Med 2008 34:431.

33. Bergeron N, Dubois MJ, Dumont M, et al. Intensive Care Delirium Screening Checklist: evaluation of a newscreening tool. Intensive Care Med 2001 27:859.

34. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1990263:1097.

35. Bliwise DL. What is sundowning? J Am Geriatr Soc 1994 42:1009.

36. Salerno D, Marik PE, Daskalakis C, et al. The role of head computer tomographic scans on the

management of MICU patients with neurological dysfunction. J Intensive Care Med 2009 24:372.37. Benbadis SR, Sila CA, Cristea RL. Mental status changes and stroke. J Gen Intern Med 1994 9:485.

38. Naughton BJ, Moran M, Ghaly Y, Michalakes C. Computed tomography scanning and delirium in elderpatients. Acad Emerg Med 1997 4:1107.

39. Oldenbeuving AW, de Kort PL, Jansen BP, et al. Delirium in the acute phase after stroke: incidence, riskfactors, and outcome. Neurology 2011 76:993.

40. Sheth RD, Drazkowski JF, Sirven JI, et al. Protracted ictal confusion in elderly patients. Arch Neurol 200663:529.

41. Veran O, Kahane P, Thomas P, et al. De novo epileptic confusion in the elderly: a 1-year prospective study.Epilepsia 2010 51:1030.

42. Koponen H, Hurri L, Stenbck U, et al. Computed tomography findings in delirium. J Nerv Ment Dis 1989177:226.

43. Hufschmidt A, Shabarin V. Diagnostic yield of cerebral imaging in patients with acute confusion. ActaNeurol Scand 2008 118:245.

44. Morandi A, Gunther ML, Vasilevskis EE, et al. Neuroimaging in delirious intensive care unit patients: apreliminary case series report. Psychiatry (Edgmont) 2010 7:28.

45. Warshaw G, Tanzer F. The effectiveness of lumbar puncture in the evaluation of delirium and fever in thehospitalized elderly. Arch Fam Med 1993 2:293.

46. Metersky ML, Williams A, Rafanan AL. Retrospective analysis: are fever and altered mental statusindications for lumbar puncture in a hospitalized patient who has not undergone neurosurgery? Clin InfectDis 1997 25:285.

47. Jacobson SA, Leuchter AF, Walter DO, Weiner H. Serial quantitative EEG among elderly subjects withdelirium. Biol Psychiatry 1993 34:135.

48. Hemphill JC. Disorders of consciousness in systemic diseases. In: Neurology and general medicine,Aminoff, MJ (Ed), Churchill Livingstone, 2001. p.1053.

49. Privitera M, Hoffman M, Moore JL, Jester D. EEG detection of nontonic-clonic status epilepticus in patientswith altered consciousness. Epilepsy Res 1994 18:155.

50. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEGmonitoring in critically ill patients. Neurology 2004 62:1743.

51. Fisch BJ, Klass DW. The diagnostic specificity of triphasic wave patterns. Electroencephalogr ClinNeurophysiol 1988 70:1.

52. Young GB. Metabolic and inflammatory cerebral diseases: electrophysiological aspects. Can J Neurol Sci

1998 25:S16.

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GRAPHICS

Common causes of delirium and confusional states

Drugs and toxins

Prescription medications (eg, opioids, sedative-hypnotics, antipsychotics, lithium, skeletal muscle

relaxers, polypharmacy)

Non-prescription medications (eg, antihistamines)

Drugs of abuse (eg, ethanol, heroin, hallucinogens, nonmedicinal use of prescription medications)

Withdrawal states (eg, ethanol, benzodiazepines)

Medication side effects (eg, hyperammonemia from valproic acid, confusion from quinolones,

serotonin syndrome)

Poisons:

Atypical alcohols (ethylene glycol, methanol)

Inhaled toxins (carbon monoxide, cyanide, hydrogen sulfide)

Plant-derived (eg, Jimson weed, Salvia)

Infections

Sepsis

Systemic infections fever-related delirium

Metabolic derangements

Electrolyte disturbance (elevated or depressed): sodium, calcium, magnesium, phosphate

Endocrine disturbance (depressed or increased): thyroid, parathyroid, pancreas, pituitary, adrenal

Hypercarbia

Hyperglycemia and hypoglycemia

Hyperosmolar and hypoosmolar states

Hypoxemia

Inborn errors of metabolism: porphyria, Wilson's disease, etc.

Nutritional: Wernicke's encephalopathy, vitamin B12 deficiency, possibly folate and niacin

deficiencies

Brain disorders

CNS infections: encephalitis, meningitis, brain or epidural abscess

Epileptic seizures, especially nonconvulsive status epilepticus*

Head injury*

Hypertensive encephalopathy

Psychiatric disorders*

Systemic organ failure

Cardiac failure

Hematologic: thrombocytosis, hypereosinophilia, leukemic blast cell crisis, polycythemia


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Liver failure: acute, chronic

Pulmonary disease, including hypercarbia and hypoxemia

Renal failure: acute, chronic

Physical disorders

Burns

Electrocution

Hyperthermia

Hypothermia

Trauma: with systemic inflammatory response syndrome, *head injury, fat embolism

* Disorders that, while not truly systemic or "medical", may produce the clinical picture of delirium or

confusional state in all other aspects.

Graphic 59893 Version 3.0


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Drugs believed to cause or prolong delirium or confusional states*

Analgesics

Nonsteroidal anti-inflammatory agents

Opioids (especially meperidine)

Antibiotics and antivirals

Acyclovir

Aminoglycosides

Amphotericin B

Antimalarials

Cephalosporins

Cycloserine

Fluoroquinolones

Isoniazid

Interferon

Linezolid

Macrolides

Metronidazole

Nalidixic acid

Penicillins

Rifampin

Sulfonamides

Anticholinergics

Atropine

Benztropine

Diphenhydramine

Scopolamine

Trihexyphenidyl

Anticonvulsants

Carbamazepine

Levetiracetam

Phenytoin

Valproate

Vigabatrin

Antidepressants

Corticosteroids

Dopamine agonists

Amantadine

BromocriptineLevodopa

Pergolide

Pramipexole

Ropinirole

Gastrointestinal agents

Antiemetics

Antispasmodics

Histamine-2 receptor blockers

Loperamide

Herbal preparations

Atropa belladonna extract

Henbane

Mandrake

Jimson weed

St. John's Wort

Valerian

Hypoglycemics

Hypnotics and sedatives

Barbiturates

Benzodiazepines

Muscle relaxants

Baclofen

Cyclobenzaprine

Other CNS-active agents

Disulfiram

Cholinesterase inhibitors (eg, donepezil)

Interleukin-2

Lithium


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Mirtazapine

Selective serotonin reuptake inhibitors

Tricyclic antidepressants

Cardiovascular and hypertension drugs

Antiarrhythmics

Beta blockers

Clonidine

Digoxin

Diuretics

Methyldopa

Phenothiazines

* Not exhaustive, all medications should be considered.



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Bedside tests of attention

Test Directions Scoring

Digit

span

Ask the subject to listen carefully and repeat a series of random

numbers. Begin with a string of 2 digits, then increase. Read each

number in a normal tone of voice at a rate of one digit per second,

taking care not to group digits in pairs or sequences that could aidrepetition eg, 3 - 52 - 8 - 18 - 4 - 9 - 36 - 3 - 8 - 5 - 15 - 7 - 2 - 9 -

4 - 68 - 1 - 9 - 2 - 7 - 5 - 6

Inability to

repeat a string

of at least five

digits indicatesprobable

impairment.

Vigilance

"A" test

Read a list of 60 letters, among which the letter "A" appears with

greater than random frequency. The subject is required to indicate

(eg, by tapping on the desk) whenever the target letter is spoken by

the examiner. The letter list is read in a normal tone at a rate of one

letter per second eg, L T P E A O A I C T D A L A A N I A B F S A M R A

E O Z D P A K A L U C J T A E O

Count errors of

omission and

commission.

More than two

errors is

considered

abnormal.



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Confusion assessment method (CAM) for the diagnosis of delirium*

Feature Assessment

1. Acute onset

and fluctuating

course

Usually obtained from a family member or nurse and shown by positive

responses to the following questions:

"Is there evidence of an acute change in mental status from the patient's

baseline?"

"Did the abnormal behavior fluctuate during the day, that is, tend to come and

go, or increase and decrease in severity?"

2. Inattention Shown by a positive response to the following:

"Did the patient have difficulty focusing attention, for example, being easily

distractible or having difficulty keeping track of what was being said?"

3. Disorganized

thinking

Shown by a positive response to the following:

"Was the patient's thinking disorganized or incoherent, such as rambling or

irrelevant conversation, unclear or illogical flow of ideas, or unpredictableswitching from subject to subject?"

4. Altered level

of

consciousness

Shown by any answer other than "alert" to the following:

"Overall, how would you rate this patient's level ofconsciousness?"

Normal = alert

Hyperalert = vigilant

Drowsy, easily aroused = lethargic

Difficult to arouse = stupor

Unarousable = coma

*The diagnosis of delirium requires the presence of features 1 AND 2 plus either 3 OR 4.



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Disclosures:Joseph Francis, Jr, MD, MPH Nothing to disclose. G Bryan Young, MD, FRCPC Nothing to disclose. Michael J

Aminoff, MD, DSc Equity Ownership/Stock Options: Trust, which is independently managed by a financial company. The portfolio may

include medical or drug companies. Kenneth E Schmader, MD Grant/Research/Clinical Trial Support: Merck [Herpes zoster (Zostervaccine)]. Janet L Wilterdink, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a

multi-level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

Disclosures
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