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.