emedicine.medscape.com

Delirium 
Updated: Mar 21, 2018
Author: Kannayiram Alagiakrishnan, MD, MBBS, MPH, MHA; Chief Editor: Randon S Welton, MD 

Overview

Practice Essentials
Delirium is defined as a transient, usually reversible, cause of mental dysfunction and manifests clinically with a wide range of
neuropsychiatric abnormalities. It can occur at any age, but it occurs more commonly in patients who are elderly and have a
previously compromised mental status.

Signs and symptoms

The clinical hallmarks of delirium are decreased attention or awareness and a change in baseline cognition. Delirium often
manifests as a waxing and waning type of confusion. Symptoms include the following:

Clouding of consciousness

Difficulty maintaining or shifting attention

Disorientation

Illusions

Hallucinations

Fluctuating levels of consciousness

Dysphasia

Dysarthria

Tremor

Asterixis in hepatic encephalopathy and uremia

Motor abnormalities

See Clinical Presentation for more detail.

Diagnosis

The diagnosis of delirium is clinical. No laboratory test can diagnose delirium.

Diagnostic criteria

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for delirium is as follows[1] :

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

Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) that is not better
accounted for by a preexisting, established, or evolving dementia.
 The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.

There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a direct
physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more than one
cause.

Assessment instruments

Some of the measures used to identify delirium include the following:

Confusion Assessment Method (CAM)

Delirium Symptom Interview (DSI)

Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)

Intensive Care Delirium Screening Checklist (ICDSC)

Delirium symptom severity can be assessed by the Delirium Detection Scale (DDS) and the Memorial Delirium Assessment
Scale (MDAS).

See Workup for more detail.

Management

The goal of treatment is to determine the cause of the delirium and stop or reverse it. Components of delirium management
include supportive therapy and pharmacologic management.

Fluid and nutrition should be given carefully because the patient may be unwilling or physically unable to maintain a balanced
intake. For the patient suspected of having alcohol toxicity or alcohol withdrawal, management should include multivitamins,
especially thiamine.

Reorientation techniques or memory cues such as a calendar, clocks, and family photos may be helpful. The environment should
be stable, quiet, and well-lighted.

Delirium that causes injury to the patient or others should be treated with medications. The most common medications used are
antipsychotic medications. Benzodiazepines often are used for withdrawal states.

See Treatment and Medication for more detail.

Background
Delirium is a transient global disorder of cognition. The condition is a medical emergency associated with increased morbidity
and mortality rates. Early diagnosis and resolution of symptoms are correlated with the most favorable outcomes. 

Delirium is not a disease but a syndrome with multiple causes that result in a similar constellation of signs and symptoms.
Delirium is defined as a transient, usually reversible, cause of mental dysfunction and manifests clinically with a wide range of
neuropsychiatric abnormalities. The clinical hallmarks are decreased awareness and attention span and a waxing and waning
type of confusion.

Delirium is often unrecognized or misdiagnosed as dementia, depression, mania, psychotic disorders, or a typical response of
the aging brain to hospitalization.  

Pathophysiology
Based on the level of psychomotor activity, delirium can be described as hyperactive, hypoactive, or mixed. Hyperactive delirium
is observed in patients in a state of alcohol withdrawal or intoxication with phencyclidine (PCP), amphetamine, and lysergic acid
diethylamide (LSD). These patients often exhibit agitation, restlessness, hallucinations, or delusions. Hypoactive delirium is
observed in patients in states of hepatic encephalopathy and hypercapnia and may be more common in older adults. Hypoactive
delirium presents with lethargy, drowsiness, apathy, decreased responsiveness, or slowed motor skills. In mixed delirium,
individuals display either relatively normal levels of psychomotor activity or rapidly fluctuating levels of activity.[1, 2]

The mechanism of delirium still is not fully understood. Delirium results from a wide variety of structural or physiological insults.
The neuropathogenesis of delirium has been studied in patients with hepatic encephalopathy and alcohol withdrawal. Research
in these areas still is limited. The main hypothesis is reversible impairment of cerebral oxidative metabolism and multiple
neurotransmitter abnormalities. The following observations support the hypothesis of multiple neurotransmitter abnormalities.
[3]

Acetylcholine

Data from animal and clinical studies support the hypothesis that acetylcholine is one of the critical neurotransmitters in the
pathogenesis of delirium.[4] A small prospective study among patients who have undergone elective hip replacement surgery
showed reduced preoperative plasma cholinesterase activity in as many as one quarter of patients. In addition, reduced
preoperative cholinesterase levels were significantly correlated with postoperative delirium.[5]

Clinically, good reasons support this hypothesis. Anticholinergic medications are a well-known cause of acute confusional
states, and patients with impaired cholinergic transmission, such those with Alzheimer disease, are particularly susceptible. In
patients with postoperative delirium, serum anticholinergic activity may be increased.[6]

Dopamine

In the brain, a reciprocal relationship exists between cholinergic and dopaminergic activities. In delirium, an excess of
dopaminergic activity occurs. Symptomatic relief occurs with antipsychotic medications such as haloperidol and other
neuroleptic dopamine blockers.

Other neurotransmitters

Serotonin: Human and animal studies have found that serotonin is increased in patients with hepatic encephalopathy and septic
delirium. Hallucinogens such as LSD act as agonists at the site of serotonin receptors. Serotonergic agents also can cause
delirium.

Gamma-aminobutyric acid (GABA): In patients with hepatic encephalopathy, increased inhibitory GABA levels also are observed.
An increase in ammonia levels occurs in patients with hepatic encephalopathy, which causes an increase in the amino acids
glutamate and glutamine, which are precursors to GABA. Decreases in CNS GABA levels are observed in patients with delirium
resulting from benzodiazepine and alcohol withdrawal.

Cortisol and beta-endorphins: Delirium has been associated with the disruption of cortisol and beta-endorphin circadian
rhythms. This mechanism has been suggested as a possible explanation for delirium caused by exogenous glucocorticoids.

Disturbed melatonin disturbance has been associated with sleep disturbances in delirium.[7]

Inflammatory mechanism

Recent studies have suggested a role for cytokines, such as interleukin-1 and interleukin-6, in the pathogenesis of delirium.
Following a wide range of infectious, inflammatory, and toxic insults, endogenous pyrogen, such as interleukin-1, is released
from the cells. Head trauma and ischemia, which frequently are associated with delirium, are characterized by brain responses
that are mediated by interleukin-1 and interleukin-6.[8, 9]

Stress reaction mechanism

Studies indicate psychosocial stress and sleep deprivation facilitate the onset of delirium.

Structural mechanism

The specific neuronal pathways that cause delirium are unknown. Imaging studies of metabolic (eg, hepatic encephalopathy)
and structural (eg, traumatic brain injury, stroke) factors support the hypothesis that certain anatomical pathways may play a
more important role than others. The reticular formation and its connections are the main sites of arousal and attention. The
dorsal tegmental pathway projecting from the mesencephalic reticular formation to the tectum and the thalamus is involved in
delirium.

Disrupted blood-brain barrier can allow neurotoxic agents and inflammatory cytokines to enter the brain and may cause delirium.
Contrast-enhanced MRI can be used to assess the blood-brain barrier.[10, 11]
Visuoperceptual deficits in delirium such as hallucinations and delusions are not due to the underlying cognitive impairment.[12]
Visual hallucinations during alcohol-withdrawal delirium are seen in subjects with polymorphisms of genes coding for dopamine
transporter and catechol-O-methyltransferase (COMT).[13]

Mortality/Morbidity
In patients who are admitted with delirium, mortality rates are 10-26%.[14]

Patients who develop delirium during hospitalization have a mortality rate of 22-76% and a high rate of death during the months
following discharge.[15] . In a review of 28 studies of critically ill patients the rate of death for patients with delirium was more
than doubled.[16]

In patients who are elderly and patients in the postoperative period, delirium may result in a prolonged hospital stay, increased
complications, increased cost, and long-term disability.[17]

According to one study, delirium is associated with worse survival and greater resource consumption in those with cardiac
critical illness. Among 590 patients included, the prevalence of cardiac (C)ICU delirium was 20.3%. Delirious patients were older,
had greater disease severity, required longer ICU stays (5 vs 2 days; P< .001), and had higher mortality (27% vs 3%; P< .001).[18]

Epidemiology
Frequency
Delirium is common in the United States. In a systematic review of 42 cohorts in 40 studies, 10–31% of new hospital
admissions met criteria for delirium and the incidence of developing delirium during the admission ranged from 3–29%.[19]

For patients in intensive care units the prevalence of delirium may reach as high as 80%.[2]

Prevalence of postoperative delirium following general surgery is 5–10% and as high as 42% following orthopedic surgery. As
many as 80% of patients develop delirium near death. Delirium is extremely common among nursing home residents.

Age

Delirium can occur at any age, but it occurs more commonly in patients who are elderly and have compromised mental status.
Delirium can occur on top of an underlying dementia. This diagnosis here requires not only a careful mental status but also a
thorough history from the patient's family and the staff as well as a comprehensive chart review.

Presentation

History
The diagnosis of delirium is clinical. No laboratory test can diagnose delirium. Obtaining a thorough history is essential.

Because delirious patients often are confused and unable to provide accurate information, getting a detailed history from family,
caregivers, and nursing staff is particularly important. Nursing notes can be very helpful for documentation of episodes of
disorientation, abnormal behavior, and hallucinations. Learning to record accurate and specific findings in mental status as well
as the particular time the finding was observed is imperative for the staff. Staff should not just report "he was confused."

Delirium always should be suspected when (a new onset) or an acute or subacute deterioration in behavior, cognition, or
function occurs, especially in patients who are elderly, demented, or depressed.
Patients may have visual hallucinations or persecutory delusions as well as grandiose delusions.

Some patients with delirium also may become suicidal or homicidal. Therefore, they should not be left unattended or alone.

Delirium is mistaken for dementia or depression, especially when patients are quiet or withdrawn. However, by Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM5) criteria, dementia cannot be diagnosed with certainty when delirium
is present. Health professionals can do Mini-Mental Status Exam (MMSE),[20] depression assessment screening using DSM-5
criteria,[1] or the Geriatric Depression Scale (GDS).[21] They can also assess for suicidal and homicidal risk if necessary. Health
professionals can directly ask patients about suicidal or homicidal ideation (thoughts), intent, and plan.

Depression symptoms are commonly seen with delirium. In a recent study, patients having symptoms of dysphoric mood and
hopelessness are at risk for incident delirium while in the hospital.[22] On the other hand, hypoactive delirium may be mistaken
for depression. Up to 42% of patients referred to psychiatry services for suspected depressive illness in the hospital may have
delirium.[23] Screening for depression in the presence of delirium is quite challenging.

Delirium is a common cause for psychotic symptoms, bizarre delusions, abnormal behavior, and thought disorders. Agitated
patients are at risk for violent and abnormal behavior and in rare circumstances, agitation can lead to attempts of homicide.

The mental status is a bedside or interview assessment that dramatically fluctuates. It includes the patient's appearance, affect
(mood), thoughts (especially the presence of hallucinations and delusions), inquiry into self-destructive behavior, homicidal
behavior, judgment and, in this diagnosis, orientation, immediate, recent, and long-term memory.

Delirium develops in a short period of time (within hours), and an acute change in consciousness or difficulty focusing on what
was being said could occur during the interview. Disturbance of the sleep-wake cycle with insomnia, daytime drowsiness, or
disturbing dreams or nightmares can also occur. Patients are often unable to remember why they are in the hospital or the
events that occurred during the delirious period (for most patients, it is like a blackout period).

Patients may have false beliefs or thinking (misinterpreting intravenous lines as ropes or snakes) or see or hear things that are
not present (picking up things in the air or seeing bugs in the bedclothes). Patients may also misjudge their level of wellness and
try to elope from the hospital. Emotional disturbances leading to depression, anxiety, fear, and irritability may be seen in some
patients. Delirium in hospitalized seniors may result in the self-removal of catheters or intravenous tubing or attempts to get out
of bed, resulting in a fall or injury.

The main symptoms of delirium include the following:

Clouding of consciousness

Difficulty maintaining or shifting attention

Disorientation

Illusions

Hallucinations

Fluctuating levels of consciousness

Symptoms tend to fluctuate over the course of the day, with some improvement in the daytime and maximum
disturbance at night. Reversal of the sleep-wake cycle is common.

Neurological symptoms may include the following:

Dysphasia

Dysarthria

Tremor

Asterixis in hepatic encephalopathy and uremia

Motor abnormalities

Patients with delirium who are hyperactive have an increased state of arousal, psychomotor abnormalities, and hypervigilance.
In contrast, patients with delirium who are hypoactive are withdrawn, less active, and sleepy.

Hypoactive delirium sometimes is misdiagnosed as dementia or depression.

In patients who are elderly, delirium often is the presenting symptom of an underlying illness.
Subsyndromal delirium has been defined as the presence of some core diagnostic symptoms that do not meet the criteria for
diagnostic threshold. Prevalence rates of 30-50% have been reported in intensive care units.[24, 25]

A prodromal phase lasting for hours to days can occur before full syndromal delirium becomes evident. This includes sleep
disturbances, vivid dreams, frequent calls for assistance, and anxiety.[24, 25]

Physical
A careful and complete physical examination including a mental status examination is necessary. Testing vital signs such as
temperature, pulse, blood pressure, and respiration is mandatory.

Patients have difficulty sustaining attention, problems in orientation and short-term memory, poor insight, and impaired
judgment. Key elements here are fluctuating levels of consciousness.

Impaired attention can be assessed with bedside tests that require sustained attention to a task that has not been memorized,
such as reciting the days of the week or months of the year backwards, counting backwards from 20, or doing serial subtraction.

DSM-5 diagnostic criteria for delirium[1] is as follows:

Disturbance of consciousness (ie, reduced clarity of awareness of the environment) occurs, with reduced ability to focus,
sustain, or shift attention.

Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) occurs that is not
better accounted for by a preexisting, established, or evolving dementia.

The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.

Evidence from the history, physical examination, or laboratory findings is present that indicates the disturbance is caused
by a direct physiologic consequence of a general medical condition, an intoxicating substance, medication use, or more
than one cause.

Other diagnostic instruments are the Delirium Symptom Interview (DSI) and the Confusion Assessment Method (CAM).[26]

Delirium symptom severity can be assessed by the Delirium Rating Scale (DRS) and the Memorial Delirium Assessment Scale
(MDAS).

Table 1. Differentiating Features of Delirium and Dementia (Open Table in a new window)

Features Delirium Dementia

Onset Acute Insidious

Course Fluctuating Progressive

Duration Days to weeks Months to years

Consciousness Altered Clear

Attention Impaired Normal, except in severe dementia

 Psychomotor changes Increased or decreased Often normal

Reversibility Usually Rarely

To make an accurate diagnosis, periodic application of diagnostic criteria such as CAM or DSM5 criteria and knowledge of the
patient's baseline mental status is imperative.

Gaps in the medical record such as once daily cognitive assessment or no formal assessments on the hallmarks of delirium
(attention span and fluctuation) may make diagnosing the condition more difficult.  The physicians depend on health records
(nursing notes) to identify a fluctuating course. The type of information might also be less than adequate for developing a timely
diagnosis. So the recognition of delirium can be delayed by infrequent observation or documentation.[27]

A simple cognitive test like the Mini-Cog can be a predictor of inhospital delirium. At the time of admission to the hospital, if the
elderly patient does not have a history of dementia or cognitive impairment, the Mini-Cog can be used to identify patients at high
risk for inhospital delirium.

The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) offers the clinician the opportunity to identify delirium
in critical care patients, especially patients on mechanical ventilation. The CAM-ICU makes use of nonverbal assessments to
evaluate the important features of delirium.

Another instrument that can be used in ICU settings is the Intensive Care Delirium Screening Checklist (ICDSC). The severity of
delirium in the ICU can be estimated by the Delirium Detection Scale (DDS).

A 2012 meta-analysis showed a sensitivity of 75.5% and specificity of 95.8% for CAM-ICU, whereas sensitivity and specificity for
the ICDSC were 80.1% and 74.6%, respectively. These results suggest the CAM-ICU is one of the most specific bedside tests that
can be used to diagnose delirium in ICU patients.[28]

The CAM-S was developed for measuring the severity of delirium in hospitalized patients (short form) and those in research
settings (long form).[29, 30]  Developers reported good psychometric properties, high interrater reliability, and strong
associations with important clinical outcomes with this tool, which is based on the standardized and validated Confusion
Assessment Method (CAM) that screens for the presence—but not the severity—of delirium. The CAM-S was tested in 2
independent cohorts at 3 academic centers comprising 300 patients scheduled for major surgery and 919 medical patients (all
patients aged ≥70 y).[29, 30]

Causes
Almost any medical illness, intoxication, or medication can cause delirium. Often, delirium is multifactorial in etiology, and the
physician treating the delirium should investigate each cause contributing to it. Medications are the most common reversible
cause of delirium.

Some of the other common reversible causes include the following:

Hypoxia

Hypoglycemia

Hyperthermia

Anticholinergic delirium

Alcohol or sedative withdrawal

Other causes of delirium include the following:

Infections
 Metabolic abnormalities

Structural lesions of the brain

Postoperative states

Miscellaneous causes, such as sensory deprivation, sleep deprivation, fecal impaction, urinary retention, and change of
environment

In persons who are elderly, medications at therapeutic doses and levels can cause delirium.

Although numerous risk factors have been described, a recent study identified 5 important independent risk factors.

Use of physical restraints

Malnutrition

Use of a bladder catheter

Any iatrogenic event

Use of 3 or more medications

Dementia is one of the strongest most consistent risk factors. Underlying dementia is observed in 25-50% of patients. The
presence of dementia increases the risk of delirium 2-3 times. Low educational level, which may be an indicator of low cognitive
reserve, is associated with increased vulnerability to delirium.

Dysphoric mood and hopelessness are also risk factors for incident delirium.

Structural changes that may contribute to delirium include the following:

Closed head injury or cerebral hemorrhage

Cerebrovascular accidents, such as cerebral infarction, subarachnoid hemorrhage, and hypertensive encephalopathy

Primary or metastatic brain tumors

Brain abscess

Metabolic causes may include the following:

Fluid and electrolyte abnormalities, acid-base disturbances, and hypoxia

Hypoglycemia

Hepatic or renal failure

Vitamin deficiency states (especially thiamine and cyanocobalamin)

Endocrinopathies associated with the thyroid and parathyroid

Hypoperfusion states such as shock congestive heart failure, cardiac arrhythmias, and anemias may contribute to delirium.

Infectious causes may include the following:

CNS infections such as meningitis

Encephalitis

HIV-related brain infections

Septicemia

Pneumonia

Urinary tract infections

Substance intoxication  with alcohol, heroin, cannabis, PCP, and LSD may cause symptoms of delirium. Withdrawal from these
substances may also contribute.
Medication-induced delirium can be caused by any of the following agents:

Anticholinergics (Benadryl, tricyclic antidepressants)

Narcotics (meperidine)

Sedative hypnotics (benzodiazepines)

Histamine-2 (H2) blockers (cimetidine)

Corticosteroids

Centrally acting antihypertensives (methyldopa, reserpine)

Anti-Parkinson drugs (levodopa)

Other causes may include postictal state and unfamiliar environment.

Delirium may come about as a result of surgery or operation.

Preoperative (dementia, polypharmacy, fluid and electrolyte imbalance)

Intraoperative (meperidine, long-acting benzodiazepines, anticholinergics such as atropine; however, medications such
as glycopyrrolate can be used because, in contrast to atropine, they do not cross the blood brain barrier)

Postoperative (hypoxia, hypotension, drug withdrawal)

Mild cognitive impairment and vascular risk factors can be independent risk factors for postoperative delirium.[31]

Drugs are a common risk factor for delirium, and drug-induced delirium is commonly seen in medical practice, especially in
hospital settings. The risk of anticholinergic toxicity is greater in elderly persons, and the risk of inducing delirium by
medications is high in frail, elderly persons and in those with dementia.

DDx

Diagnostic Considerations
Dementia

AIDS-related complex

Psychosis

Dementia is one of the most important risk factors for delirium. It often coexists in patients who are hospitalized. Delirium may
be a risk factor or marker for the development of dementia. The safest rule is to consider delirium when recent changes in an
elderly patient's level of consciousness and cognition have occurred in an acute care setting.

Patients with hypoactive withdrawn delirium may be misdiagnosed as depressed. Depressed patients also may have cognitive
symptoms, but the patient's level of consciousness is normal.

Delirium may have to be differentiated from psychotic illnesses such as schizophrenia because both have psychotic features. In
delirium, the patient often does not have a previous history of serious psychiatric illness. The onset of symptoms of delirium is
acute or subacute, the hallucinations predominantly are visual and fluctuate, and the patient has impaired memory and
orientation and clouding of consciousness.

Differential Diagnoses
Depression

Workup
 
Workup

Laboratory Studies
Laboratory tests that may be helpful for diagnosis include the following:

Complete blood cell count with differential - Helpful to diagnose infection and anemia

Electrolytes - To diagnose low or high levels

Glucose - To diagnose hypoglycemia, diabetic ketoacidosis, and hyperosmolar nonketotic states

Renal and liver function tests - To diagnose liver and renal failure

Thyroid function studies - To diagnose hypothyroidism

Urine analysis - Used to diagnose urinary tract infection

Urine and blood drug screen - Used to diagnose toxicological causes

Thiamine and vitamin B-12 levels - Used to detect deficiency states of these vitamins

Tests for bacteriological and viral etiologies including syphilis

Sedimentation rate

Drug screen including alcohol level

HIV tests

Tests for other infectious causes if necessary or clinically indicated (These tests are not performed routinely, even
though 30-40% of hospitalized patients with HIV infection develop delirium during hospitalization.[32] )

Serum marker for delirium: The calcium-binding protein S-100 B could be a serum marker of delirium. Higher levels are
seen in patients with delirium when compared to patients without delirium.[33]

Imaging Studies
See the list below:

Neuroimaging

Perform CT scan of the head.

Magnetic resonance imaging (MRI) of the head may be helpful in the diagnosis of stroke, hemorrhage, and
structural lesions.

Electroencephalogram

In delirium, generally, slowing of the posterior dominant rhythm and increased generalized slow-wave activity are
observed on electroencephalogram (EEG) recordings.

In delirium resulting from alcohol/sedative withdrawal, increased EEG fast-wave activity occurs.

In patients with hepatic encephalopathy, diffuse EEG slowing occurs.

The type of patterns observed includes triphasic waves in toxicity or metabolic derangement, continuous
discharges in nonconvulsive status epilepticus, and localized delta activity in focal lesions.

Chest radiograph is used to diagnose pneumonia or congestive heart failure.

Other Tests
Lumbar puncture is indicated when CNS infection is suspected as a cause of delirium or when the source for the systemic
infection cannot be determined.

Pulse oximetry is used to diagnose hypoxia as a cause of delirium.

Electrocardiogram is used to diagnose ischemic and arrhythmic causes.

Treatment

Medical Care
When delirium is diagnosed or suspected, the underlying causes should be sought and treated. Despite every effort, no cause
for delirium can be found in a small percentage of patients. Components of delirium management include supportive therapy
and pharmacological management.

Fluid and nutrition should be given carefully because the patient may be unwilling or physically unable to maintain a balanced
intake. For the patient suspected of having alcohol toxicity or alcohol withdrawal, therapy should include multivitamins,
especially thiamine.

Reorientation techniques or memory cues such as a calendar, clocks, and family photos may be helpful. The environment should
be stable, quiet, and well-lighted. One study showed a reduction of sound during the night by using earplugs in the ICU setting
decreased the risk of delirium by 53%, and improved the self-reported sleep perception of the patient for 48 hours.[34] Sensory
deficits should be corrected, if necessary, with eyeglasses and hearing aids. Family members and staff should explain
proceedings at every opportunity, reinforce orientation, and reassure the patient. Support from a familiar nurse and family
should be encouraged. A meta-analysis of 7 studies that focused on the usefulness of interventions such as physical or
occupational therapy, daily reorientation, and the avoidance of sensorial deprivation found a significant reduction in the
development of delirium among elderly inpatients.[35]

Physical restraints should be avoided. Delirious patients may pull out intravenous lines, climb out of bed, and may not be
compliant. Perceptual problems lead to agitation, fear, combative behavior, and wandering. Severely delirious patients benefit
from constant observation (sitters), which may be cost effective for these patients and help avoid the use of physical restraints.
These patients should never be left alone or unattended.

Consultations
Psychiatric consultation may be indicated for management of behavioral problems such as agitation or aggressive behavior.

Medication

Medication Summary
Delirium that causes injury to the patient or others should be treated with medications. The most common medications used are
antipsychotic medications. While this is a common and seemingly useful strategy, the literature is still mixed. A 2015 meta-
analysis of 15 studies found that second-generation antipsychotics (SGAs) may treat delirium better than placebo, usual care, or
haloperidol.[36]  A 2016 meta-analysis of 19 studies found that antipsychotic use was not associated with change in delirium
duration, severity, or hospital or ICU length of stay.[37]

Benzodiazepines often are used for alcohol and benzodiazepine withdrawal states.

Since decreased anticholinergic activity may be associated with delirium, anticholinesterase inhibitors have been tried. Even
though case reports showed evidence that cholinesterase inhibitors may play a role in the management of delirium, larger trials
and systematic review did not support this use.[38]  A randomized, double-blinded, placebo-controlled, multicenter trial in
intensive care unit patients showed rivastigmine did not decrease duration of delirium and increased mortality in these patients.
In this trial, the study group had more sicker patients with emergency admissions to the ICU, and this trial had used IV
haloperidol, lorazepam, or propofol, in addition to rivastigmine, which might also have contributed to the delirium and increased
mortality.[39]  A review of 7 trials of anticholinesterase inhibitors found that in 5 of the studies there was no benefit from the
medications in either the prevention or management of delirium.[40]

Recent clinical trials showed that the melatonin supplement and its receptor agonist ramelteon may be useful in the prevention
and management of delirium. Melatonin levels were found to be altered in delirium subjects.[41] Melatonin is available over the
counter in North America. Ramelteon has been approved by the FDA for the treatment of insomnia.[42]

Antipsychotics

Class Summary
This class of drugs are the medication of choice in the treatment of psychotic symptoms of delirium. Older antipsychotics such
as haloperidol, a high-potency antipsychotic, are useful but have adverse neurological effects. Newer neuroleptics such as
risperidone, olanzapine, and quetiapine relieve symptoms while minimizing adverse effects. Initial doses may need to be higher
than maintenance doses. Use lower doses in patients who are elderly. Discontinue these medications as soon as possible.
Attempt a trial of tapering the medication once symptoms are in control. Antipsychotics can be associated with adverse
neurological effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and tardive dyskinesia. Longer term
use is also associated with metabolic syndrome. Doses should be kept as low as possible to minimize adverse effects.
Paradoxical and hypersensitivity reactions may occur.

Haloperidol (Haldol)
A butyrophenone high-potency antipsychotic. One of most effective antipsychotics for delirium. High-potency antipsychotic
medications also cause less sedation than phenothiazines and reduce risks of exacerbating delirium.

Risperidone (Risperdal)
A newer antipsychotic with fewer extrapyramidal adverse effects than Haldol. Binds to dopamine D2-receptor with 20 times
lower affinity than for 5-HT2-receptor. Improves negative symptoms of psychoses and reduces incidence of adverse
extrapyramidal effects.

Benzodiazepines

Class Summary
Reserved for delirium resulting from seizures or withdrawal from alcohol or sedative hypnotics. Coadministration with
antipsychotics is considered only in patients who tolerate lower doses of either medication or have prominent anxiety or
agitation. Benzodiazepines are preferred over neuroleptics for treatment of delirium resulting from alcohol or sedative hypnotic
withdrawal. They also may be used when unknown substances may have been ingested and may be helpful in delirium from
hallucinogen, cocaine, stimulant, or PCP toxicity. Use special precaution when using benzodiazepines because they may cause
respiratory depression, especially in patients who are elderly, those with pulmonary problems, or debilitated patients.

Lorazepam (Ativan)
Preferable because it is short acting and has no active metabolites. In addition, can be used in both IM and IV forms. When
patient needs to be sedated for longer than 24 h, this medication is excellent. Commonly used prophylactically to prevent
delirium tremens.

Vitamins

Class Summary
Patients with alcoholism and patients with malnutrition are prone to thiamine and vitamin B-12 deficiency, which can cause
delirium.

Thiamine
For alcohol withdrawal and in cases of Wernicke encephalopathy.

Cyanocobalamin (Physicians EZ Use B-12, Nascobal)

Vitamin B-12 deficiency can cause confusion or delirium in patients who are elderly. Deoxyadenosylcobalamin and
hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or
plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or
diseases of the distal ileum.

Hypnotic, Miscellaneous

Class Summary
Agents in this class may be useful in the prevention and management of delirium.

Melatonin
Melatonin is a naturally occurring hormone secreted by the pineal gland. The concentration of melatonin is highest in the blood
during normal times of sleep and lowest during normal times of wakefulness. The general consensus is that melatonin given
during normal waking hours has hypnotic properties.

Ramelteon (Rozerem)
Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are
thought to promote sleep and be involved in maintaining circadian rhythm and a normal sleep-wake cycle. Ramelteon does not
cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use. It is indicated for
insomnia characterized by difficulty with sleep onset.

 
Follow-up

Further Outpatient Care

Following recovery, patient's memories of events of the delirium are variable. Be sure to educate the patient, family, and primary
caregivers about future risk factors.

It is not unusual for patients who are elderly to require 6-8 weeks or longer for full recovery. In particular, elderly patients with
postacute care complications are at risk for prolonged and persistent delirium.[43]

Further Inpatient Care

Carefully assess patients to determine their level of care needs. Assessment should include behavior (24 h), daily mental status,
potential for injury, and underlying medical and metabolic status.

Deterrence/Prevention
Prevention should be the goal because delirium is associated with adverse outcomes and high health care costs.

A multicomponent intervention study that targeted cognitive impairment, sleep deprivation, immobility, visual impairment,
hearing impairment, and dehydration showed significant reduction in the number and duration of episodes of delirium in older
patients who were hospitalized.

Patients who are at high risk for delirium should be monitored closely as outpatients, during hospitalization, and throughout
surgical procedures.

Physicians should become familiar with prescribing practices for patients who are elderly, keeping dosages low and avoiding
medications that cause delirium.

Monitoring the patient's mental status as a vital sign helps to diagnose delirium early.

Complications
Complications of delirium may include the following:

Malnutrition, fluid and electrolyte abnormalities

Aspiration pneumonia

Pressure ulcers

Weakness, decreased mobility, and decreased function

Falls and combative behavior leading to injuries and fractures

Wandering and getting lost

Long-term cognitive impairment: Accumulating evidence shows that delirium is not only a transient, reversible acute
confusion, but also can give rise to a persistent long-term cognitive impairment.[44]
Prognosis
Delirium significantly worsens prognosis and is associated with increased mortality at discharge and at 12 months. A significant
proportion of patients with delirium during their hospital admission continued to demonstrate symptoms of delirium at
discharge, 6-month, and 12-month follow-up.[19]

Resolution of symptoms may take longer in patients with poor premorbid cognitive function, incorrect or incomplete diagnosis
of contributing factors, and structural brain diseases treated with large doses of psychoactive medications prior to the onset of
acute medical illness.

For some patients, the cognitive effects of delirium may resolve slowly or not at all.

Patient Education
Patient and family education

See the list below:

Educating families and patients regarding the etiology and course of disease is an important role for physicians.

Educate the patient, family, and primary caregivers about future risk factors.

Families may worry that the patient has brain damage or a permanent psychiatric illness. Providing reassurance that
delirium often is temporary and is the result of a medical condition may be beneficial to both patients and their families.

Suggest that family members or friends visit the patient, usually one at a time, and provide a calm and structured
environment. Encourage them to furnish some familiar objects, such as photos or a favorite blanket, to help reorient the
patient and make the patient feel more secure.

Patient and family education materials are available here:

MedlinePlus: Delirium

Merck: Delirium

Questions & Answers

Overview

What is the definition of delirium?

What are the signs and symptoms of delirium?

What are the DSM-5 diagnostic criteria for delirium?

What are psychometric measures used to identify delirium?

What are the treatment options for delirium?

What is delirium?

What causes delirium?

What role does acetylcholine play in the pathogenesis of delirium?

What is the role of dopamine in the pathogenesis of delirium?

What is the role of serotonin in the pathogenesis of delirium?

What is the role of role gamma-aminobutyric acid (GABA) in the pathogenesis of delirium?

What is the role of cortisol and beta-endorphins in the pathogenesis of delirium?

What is the role of melatonin in the pathogenesis of delirium?

What is the role of cytokines in the pathogenesis of delirium?

What is the role of stress in the pathogenesis of delirium?

What is the role of neuronal pathways in the pathogenesis of delirium?

What are the mortality rates for delirium?

What is the prognosis of delirium in cardiac critical illnesses?

What is the incidence of delirium in the US?

How does the incidence of delirium vary by age?

Presentation

Who can provide patient history when delirium is suspected?

Why should a patient with suspected delirium never be left unattended?

How is delirium differentiated from depression?

How is mental status assessed in suspected delirium?

What are the main symptoms of delirium?

What are neurological symptoms of delirium?

What do the symptoms of hyperactive delirium differ from those of hypoactive delirium?

What does delirium suggest in elderly patients?

What is subsyndromal delirium?

What is the prodromal phase of delirium?

Which tests should be included in the physical exam for delirium?

What are the DSM-5 criteria for delirium?

Which instruments can be used in the diagnosis of delirium?

How is delirium symptom severity assessed?

How are medical records used in the diagnosis of delirium?

Which instruments can be used to assess delirium in hospitalized patients?

What causes delirium?

What are the risk factors for delirium?

What are CNS structural changes that can contribute to delirium?

What are metabolic causes of delirium?

What are infectious causes of delirium?

Which substances and medication may cause delirium?

What are the surgical causes of delirium?

What is a common risk factor for delirium in the elderly?

DDX

Which conditions should be included in the differential diagnoses for delirium?

What are the differential diagnoses for Delirium?

Workup

What is the role of lab testing in the diagnosis of delirium?

What is the role of imaging studies in the diagnosis of delirium?

Which supplemental tests are performed in the workup of delirium?

Treatment

What are the treatment options for delirium?

Which specialist consultations are required for the management of delirium?

Medications

Which medications are used to treat delirium?

Which medications in the drug class Hypnotic, Miscellaneous are used in the treatment of Delirium?

Which medications in the drug class Vitamins are used in the treatment of Delirium?

Which medications in the drug class Benzodiazepines are used in the treatment of Delirium?

Which medications in the drug class Antipsychotics are used in the treatment of Delirium?

Follow-up

What care is needed following treatment of delirium?

What assessment is needed following treatment of delirium?

How is delirium prevented?

What are possible complications of delirium?

What is the prognosis of delirium?

What education about delirium should patients and families receive?

Contributor Information and Disclosures

Author

Kannayiram Alagiakrishnan, MD, MBBS, MPH, MHA Professor, Department of Medicine, Division of Geriatric Medicine,
University of Alberta Faculty of Medicine and Dentistry, Canada

Kannayiram Alagiakrishnan, MD, MBBS, MPH, MHA is a member of the following medical societies: American College of
Physicians, American Geriatrics Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy;
Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Randon S Welton, MD Associate Professor of Psychiatry, Director of Residency Training, Department of Psychiatry, Wright State
University, Boonshoft School of Medicine

Randon S Welton, MD is a member of the following medical societies: American Association of Directors of Psychiatric
Residency Training, American Psychiatric Association, Dayton Psychiatric Association, Ohio Psychiatric Physicians Association

Disclosure: Nothing to disclose.

Additional Contributors

Mohammed A Memon, MD Psychiatrist/Geriatric Psychiatrist, Carolina Center for Behavioral Health; Assistant Professor of
Psychiatry, Virginia Commonwealth University School of Medicine

Mohammed A Memon, MD is a member of the following medical societies: American Association for Geriatric Psychiatry,
American Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Acknowledgements

Patricia Blanchette, MD Department Chair and Director, Geriatric Medicine Fellowship Program, Professor of Geriatric Medicine,
John A Burns School of Medicine, University of Hawaii

Patricia Blanchette, MD is a member of the following medical societies: American College of Physicians, American Geriatrics
Society, American Medical Association, American Medical Directors Association, Gerontological Society of America, and Hawaii
Medical Association

Disclosure: Nothing to disclose.

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