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Delirium

by Juebin Huang, MD, PhD

Delirium is an acute, transient, usually reversible, fluctuating disturbance in attention, cognition, and consciousness level. Causes include almost any disorder or drug. Diagnosis is clinical, with laboratory and usually imaging tests to identify the cause. Treatment is correction of the cause and supportive measures.

Delirium may occur at any age but is more common among the elderly. At least 10% of elderly patients who are admitted to the hospital have delirium; 15 to 50% experience delirium at some time during hospitalization. Delirium is also common after surgery and among nursing home residents and ICU patients. When delirium occurs in younger people, it is usually due to drug use or a life-threatening systemic disorder.

Delirium is sometimes called acute confusional state or toxic or metabolic encephalopathy.

Etiology

The most common causes are the following:

  • Drugs, particularly anticholinergics, psychoactive drugs, and opioids

  • Dehydration

  • Infection

Many other conditions can cause delirium (see Causes of Delirium). In about 10 to 20% of patients, no cause is identified.

Predisposing factors include brain disorders (eg, dementia, stroke, Parkinson disease), advanced age, sensory impairment (eg, impaired vision or hearing), alcohol intoxication, and multiple coexisting disorders.

Precipitating factors include use of drugs (particularly 3 new drugs), infection, dehydration, shock, hypoxia, anemia, immobility, undernutrition, use of bladder catheters (whether urinary retention is present or not), hospitalization, pain, sleep deprivation, and emotional stress. Unrecognized liver or kidney failure may cause drug toxicity and delirium by impairing the metabolism and reducing the clearance of a previously well-tolerated drug.

Recent exposure to anesthesia also increases risk, especially if exposure is prolonged and if anticholinergics are given during surgery. After surgery, pain and the use of opioid analgesics can also contribute to delirium. Decreased sensory stimuli at night may trigger delirium in at-risk patients. For elderly patients in an ICU, risk of delirium (ICU psychosis) is particularly high.

Causes of Delirium

Category

Examples

Neurologic causes

Cerebrovascular disorders

Hemorrhagic stroke, ischemic stroke, transient ischemia attack

Migraine

Confusional migraine (migraine that alters consciousness)

Inflammation or infection

Acute demyelinating encephalomyelitis, brain abscess, CNS vasculitis, encephalitis, meningitis, meningoencephalitis,

Seizure disorders

Nonconvulsive status epilepticus, postictal state

Trauma

Subdural hematoma, traumatic brain injury,

Tumor

Meningeal carcinomatosis, primary or metastatic brain tumor

Nonneurologic causes

Drugs

Anticholinergics, antiemetics, antihistamines (eg, diphenhydramine), antihypertensives, antipsychotics, antispasmodics, benzodiazepines, cimetidine, corticosteroids, digoxin, dopamine agonists, hypnotics, muscle relaxants, opioids, recreational drugs, sedatives, tricyclic antidepressants

Endocrine disorders

Adrenal or pituitary insufficiency, Cushing syndrome, hyperparathyroidism, hyperthyroidism, hypothyroidism

Hematologic disorders

Hyperviscosity syndrome, leukemic blast cell crisis, polycythemia, thrombocytosis

Infections

Fever, pneumonia, sepsis, systemic infections, UTIs

Injuries

Burns, electrical injuries, fat embolism, heatstroke, hypothermia

Metabolic disorders

Acid-base disturbances, fluid and electrolyte abnormalities (eg, dehydration, hypercalcemia, hypernatremia, hypocalcemia, hyponatremia, hypomagnesemia), hepatic or uremic encephalopathy, hyperosmolality, hyperglycemia, hyperthermia, hypoglycemia, hypoxia, Wernicke encephalopathy

Vascular or circulatory disorders

Anemia, cardiac arrhythmias, heart failure, hypoperfusion states, shock

Vitamin deficiency

Thiamin deficiency, vitamin B 12 deficiency

Withdrawal syndromes

Alcohol, barbiturates, benzodiazepines, opioids

Other causes

Change of environment, fecal impaction, hypertensive encephalopathy, liver failure, long stays in an ICU, mental disorders, postoperative states, sensory deprivation, sleep deprivation, toxins that affect the CNS, urinary retention

Pathophysiology

Mechanisms are not fully understood but may involve reversible impairment of cerebral oxidative metabolism, multiple neurotransmitter abnormalities, and generation of cytokines. Stress of any kind upregulates sympathetic tone and downregulates parasympathetic tone, impairing cholinergic function and thus contributing to delirium. The elderly are particularly vulnerable to reduced cholinergic transmission, increasing their risk of delirium. Regardless of the cause, the cerebral hemispheres or arousal mechanisms of the thalamus and brain stem reticular activating system become impaired.

Symptoms and Signs

Delirium is characterized primarily by difficulty focusing, maintaining, or shifting attention (inattention). Consciousness level fluctuates; patients are disoriented to time and sometimes place or person. They may have hallucinations, delusions, and paranoia. Confusion regarding day-to-day events and daily routines is common, as are changes in personality and affect. Thinking becomes disorganized, and speech is often disordered, with prominent slurring, rapidity, neologisms, aphasic errors, or chaotic patterns.

Symptoms fluctuate over minutes to hours; they may lessen during the day and worsen at night.

Symptoms may include inappropriate behavior, fearfulness, and paranoia. Patients may become irritable, agitated, hyperactive, and hyperalert, or they may become quiet, withdrawn, and lethargic. Very elderly people with delirium tend to become quiet and withdrawn—changes that may be mistaken for depression. Some patients alternate between the two. Usually, patterns of sleeping and eating are grossly distorted. Because of the many cognitive disturbances, insight is poor, and judgment is impaired. Other symptoms and signs depend on the cause.

Diagnosis

  • Mental status examination

  • Standard diagnostic criteria to confirm delirium

  • Thorough history

  • Directed physical examination and selective testing to determine cause

Delirium, particularly in elderly patients, is often overlooked by clinicians. Clinicians should consider delirium in any elderly patient who presents with impairment in memory or attention.

Mental status examination

Patients with any sign of cognitive impairment require a formal mental status examination (see Examination of Mental Status). Attention is assessed first. Simple tests include immediate repetition of the names of 3 objects, digit span (ability to repeat 7 digits forward and 5 backward), and naming the days of the week forward and backward. Inattention (patient does not register directions or other information) must be distinguished from poor short-term memory (patient registers information but rapidly forgets it). Further cognitive testing is futile for patients who cannot register information.

After initial assessment, standard diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) or Confusion Assessment Method (CAM) may be used. The following features are required for diagnosis:

  • Acute change in cognition that fluctuates during the day

  • Inattention (eg, difficulty focusing or following what is said)

plus one of the following:

  • Disturbance of consciousness (ie, reduced clarity and awareness of the environment) with DSM

or

  • An altered level of consciousness (eg, hyperalert, lethargic, stuporous, comatose) or disorganized thinking (eg, rambling, irrelevant conversation, illogical flow of ideas) with CAM


History

History is obtained by interviewing family members, caregivers, and friends. It can determine whether the change in mental status is recent and is distinct from any baseline dementia ( Differences Between Delirium and Dementia*). The history helps distinguish a mental disorder from delirium. Mental disorders, unlike delirium, almost never cause inattention or fluctuating consciousness, and onset of mental disorders is nearly always subacute. Sundowning (behavioral deterioration during evening hours), which is common among institutionalized patients with dementia, may be difficult to differentiate; newly symptomatic deterioration should be presumed to be delirium until proved otherwise.

History should also include use of alcohol and illicit, OTC, and prescription drugs, focusing particularly on drugs with CNS effects and on new additions, discontinuations, or changes in dose, including overdosing.


Physical examination

Examination, particularly in patients who are not fully cooperative, should focus on the following:

  • Vital signs

  • Hydration status

  • Potential foci for infection

  • Skin and head and neck

  • Neurologic examination

Findings can suggest a cause. For example, fever, meningismus, or Kernig and Brudzinski signs suggest CNS infection. Tremor and myoclonus suggest uremia, liver failure, drug intoxication, or certain electrolyte disorders (eg, hypocalcemia, hypomagnesemia). Ophthalmoplegia and ataxia suggest Wernicke-Korsakoff syndrome (see Wernicke’s Encephalopathy). Focal neurologic abnormalities (eg, cranial nerve palsies, motor or sensory deficits) or papilledema suggests a structural CNS disorder. Scalp or facial lacerations, bruising, swelling, and other findings suggest head trauma.


Testing

Testing usually includes CT or MRI, tests for suspected infections (eg, CBC, blood cultures, chest x-ray, urinalysis), and measurement of electrolytes, BUN, creatinine, plasma glucose, blood levels of any drugs suspected to be having toxic effects, and a urine drug screen.

If the diagnosis is unclear, further testing may include pulse oximetry (or ABGs); liver function tests; measurement of serum calcium and albumin, thyroid-stimulating hormone (TSH), vitamin B 12 , ESR, and antinuclear antibody (ANA); and a test for syphilis (eg, rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL] test).

If the diagnosis is still unclear, testing may include CSF analysis (particularly to rule out meningitis, encephalitis, or subarachnoid hemorrhage), measurement of serum ammonia, and testing to check for heavy metals.

If nonconvulsive status epilepticus, a rare cause, is suspected (based on history, subtle motor twitches, automatisms, or presence of a steadier but less intense pattern of bewilderment and drowsiness), EEG should be done.


Prognosis

Morbidity and mortality rates are higher in patients who have delirium when they are hospitalized or who develop delirium during hospitalization; 35 to 40% of hospitalized patients with delirium die within 1 yr.

Delirium due to certain conditions (eg, hypoglycemia, drug or alcohol intoxication, infection, iatrogenic factors, drug toxicity, electrolyte imbalance) typically resolves rapidly with treatment. However, recovery may be slow (days to even weeks or months), especially in the elderly, resulting in longer hospital stays, increased risk and severity of complications, increased costs, and long-term disability. Some patients never fully recover from delirium. For up to 2 yr after delirium occurs, risk of cognitive and functional decline, institutionalization, and death is increased.

Treatment

  • Correction of the cause and removal of aggravating factors

  • Supportive care

  • Management of agitation

Correcting the cause (eg, treating infection, giving fluids and electrolytes for dehydration) and removing aggravating factors (eg, stopping drugs) may result in resolution of delirium. Nutritional deficiencies (eg, of thiamin or vitamin B 12 ) should be corrected, and good nutrition and hydration should be provided.

General measures

The environment should be stable, quiet, and well-lit and include visual cues to orient the patient (eg, calendar, clocks, family photographs). Frequent reorientation and reassurance by hospital staff or family members may also help. Sensory deficits should be minimized (eg, by replacing hearing-aid batteries, by encouraging patients who need eyeglasses or hearing aids to use them).

Approach to treatment should be interdisciplinary (with a physician, physical and occupational therapists, nurses, and social workers); it should involve strategies to enhance mobility and range of motion, treat pain and discomfort, prevent skin breakdown, ameliorate incontinence, and minimize risk of aspiration.

Agitation may threaten the well-being of the patient, a caregiver, or a staff member. Simplifying drug regimens and avoiding use of IV lines, bladder catheters, and physical restraints (particularly in the long-term care setting) as much as possible can help prevent exacerbation of agitation and reduce risk of injury. However, in certain circumstances, physical restraints may be needed to prevent patients from harming themselves or others. Restraints should be applied by a staff member trained in their use; they should be released at least every 2 h to prevent injury and discontinued as soon as possible. Use of hospital-employed assistants (sitters) as constant observers may help avoid the need for restraints.

Explaining the nature of delirium to family members can help them cope. They should be told that delirium is usually reversible but that cognitive deficits often take weeks or months to abate after resolution of the acute illness.


Drugs

Drugs, typically low-dose haloperidol (0.5 to 1.0 mg po, IV, or IM once, then repeated q 1 to 2 h as needed), may lessen agitation or psychotic symptoms; occasionally, much higher doses are necessary. However, drugs do not correct the underlying problem and may prolong or exacerbate delirium. Second-generation (atypical) antipsychotics (eg, risperidone 0.5 to 3 mg po q 12 h, olanzapine 2.5 to 15 mg po once/day) may be used instead because they have fewer extrapyramidal adverse effects; however, long-term use in patients with dementia may increase risk of stroke and death. These drugs are not typically given IV or IM.

Benzodiazepines (eg, lorazepam 0.5 to 1.0 mg po or IV once, then repeated q 1 to 2 h as needed) are the drugs of choice for delirium caused by withdrawal from alcohol or benzodiazepines. Their onset of action is more rapid (5 min after parenteral administration) than antipsychotics. Benzodiazepines should be avoided if delirium results from other conditions because these drugs worsen confusion and sedation.


Prevention

Because delirium greatly worsens prognosis for hospitalized patients, prevention should be emphasized. Hospital staff members should be trained to take measures to maintain orientation, mobility, and cognition and to ensure sleep, good nutrition and hydration, and sufficient pain relief, particularly in elderly patients. Family members can be encouraged to help with these strategies. The number and doses of drugs should be reduced if possible.

Key Points

  • Delirium, which is very common among hospitalized elderly patients, is often caused by drugs, dehydration, and infections (eg, UTI) but can have many other causes.

  • Consider delirium in elderly patients, particularly those presenting with impaired memory or attention.

  • History taken from family members, caregivers, and friends and mental status examination are key to recognizing delirium.

  • Thoroughly assess patients with delirium for possible neurologic and systemic causes and triggers.

  • About 35 to 40% of hospitalized patients with delirium die within 1 yr.

  • Treat the cause of delirium, and provide supportive care, including sedation when necessary.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • LANOXIN
  • No US brand name
  • No US trade name
  • TAGAMET
  • RISPERDAL
  • HALDOL
  • ZYPREXA
  • ATIVAN

* This is a professional Version *