Delirium

Delirium is a neurocognitive disorder characterized by impairments in attention and awareness (reduced orientation to the environment), as well as other cognitive disturbances (e.g., in memory, language, or perception). Symptoms develop acutely and tend to fluctuate throughout the day. Delirium occurs most commonly in older patients and is typically secondary to another medical condition or polypharmacy. As delirium is common in critically ill patients, prevention is also part of supportive care in the ICU. Although delirium is a reversible confusional state, it warrants urgent medical attention because it may be the first sign of serious underlying disease. Management of delirium focuses on treating the underlying illness and providing supportive care until the confusion resolves. Antipsychotic medications may be used to manage agitation if other measures fail.

• Delirium: a syndrome of acute confusion characterized by fluctuations in awareness, cognition, and attention, that fulfills the diagnostic criteria (e.g., DSM-5 or “Confusion assessment method” criteria) ^[1][2]
• Subsyndromal delirium: proposed term for patients with clinical features of delirium that do not fulfill the criteria for a delirium diagnosis. ^[2]
• Acute encephalopathy ^[2]
  • A pathobiological process in the brain that:
    • Is diffuse (i.e., without an associated structural lesion)
    • Develops rapidly (i.e., within hours to days, but < 4 weeks)
    • Can manifest as delirium, stupor, or coma
  • Can be further specified according to the suspected underlying mechanism, e.g., acute toxic-metabolic encephalopathy

Delirium is typically secondary to another medical condition or polypharmacy. The following is a nonexhaustive list of common causes of delirium.

Metabolic diseases

• Most common cause; also referred to as metabolic encephalopathy
• Etiologies include:
  • Liver or kidney failure
  • Diabetes mellitus (diabetic ketoacidosis)
  • Hyperthyroidism or hypothyroidism
  • Vitamin deficiencies (e.g., vitamin B₁₂ deficiency, folic acid deficiency, thiamine deficiency)
  • Electrolyte abnormalities

Infection

• UTIs (most common cause in older patients)
• Pneumonia
• Meningitis

CNS pathology

• Ischemic stroke
• Intracranial hemorrhage
• Brain tumor

Drugs (drug-induced cognitive impairment) and toxins (toxic encephalopathy)

• Anticholinergics
• Benzodiazepines, barbiturates
• Antidepressants and antipsychotics (especially those with anticholinergic activity, e.g., quetiapine)
• Antihistamines (particularly in older patients)
• Opioids
• Diuretics (may cause electrolyte abnormalities)
• Recreational drugs (intoxication/withdrawal)
• Alcohol use disorder and alcohol withdrawal
• Heavy metals (e.g., arsenic, lead, mercury)

Cardiorespiratory conditions

• Hypoxia (e.g., anemia, pulmonary embolism)
• Hypercapnia (e.g., COPD)
• Acute cardiovascular disease
  • Myocardial infarction
  • Shock
  • Acute heart failure
• Dehydration

Other

• Constipation
• Urinary retention
• Major surgery
• Trauma (e.g., hip fracture, traumatic brain injury)
• Pain
• Sleep deprivation
• Hearing or vision loss

Pediatric, older (> 65 years), and hospitalized patients are particularly susceptible to delirium. ^[3][4][5]

I WATCH DEATH: Infection, Withdrawal, Acute metabolic disorder, Trauma, CNS pathology, Hypoxia, Deficiencies, Endocrine, Acute vascular, Toxins/drugs, and Heavy metals are the major causes of delirium.

• The main symptom is an acute (hours to days) alteration in the level of awareness and attention.
• Other features may include:
  • Disorganized thinking
  • Illusions
  • Hallucinations (mostly visual)
  • Cognitive deficits (e.g., memory)
  • Reversal of the sleep-wake cycle
  • Emotional lability
  • Agitation, combativeness
  • Alterations in psychomotor activity may occur.
• The severity of symptoms fluctuates throughout the day and worsens in the evening (termed sundowning).
• Symptoms are reversible; their duration and severity depend on the underlying illness.
• Delirium is commonly described based on the type of alteration that is seen:

Delirium is diagnosed clinically, based on either the DSM 5 or Confusion Assessment Method (CAM) criteria. Further studies should be conducted to determine the underlying etiology.

Delirium should be considered a medical emergency until proven otherwise; it can be a sign of severe underlying pathology and is associated with increased mortality. ^[5]

Diagnostic criteria ^[6][7]

Confusion assessment method (CAM) ^[8]

CAM can be used in the community and most hospital environments to assess delirium; for patients in the ICU or the recovery room, use the modified version, CAM-ICU. ^[9]

DSM-5 diagnostic criteria for delirium ^[6]

The patient meets all of the following:

• Attention and awareness are impaired.
• Acute onset over hours or days with waxing and waning severity
• ≥ 1 additional disruption in cognition
• The condition fulfills the following criteria:
  • Absence of preexisting dementia, coma, or severely reduce responsiveness
  • Evidence of an organic underlying cause

Determination of the underlying etiology

Routine laboratory studies ^[7][10]

The following studies are recommended in all patients with a new presumptive delirium diagnosis.

• Complete blood count
• Serum glucose
• Electrolytes
• Urinalysis: abnormalities related to UTI (e.g., pyuria, bacteriuria) or renal failure (e.g., urinary casts)
• Urea and creatinine
• Magnesium
• Liver chemistries

Further diagnostic studies

These should be guided by clinical suspicion of the underlying process or conducted if no other cause has been identified with routine tests.

Diagnosis of delirium is clinical. Identify the underlying precipitating factors for DELIRIUM: Drugs, Electrolyte abnormalities, Lack of medication (withdrawal), Infection, Reduced sensorial input, Intracranial pathology, Urinary retention or fecal impaction, Myocardial and pulmonary disease. ^[7]

The symptoms of delirium overlap with a number of other neurological disorders, including dementia. Additionally, patients with preexisting neurological diseases such as dementia are more vulnerable to developing delirium.

Dementia

Delirium is most often confused with dementia. However, there are significant differences in the presentation of diseases.

Delirium is characterized by acute onset of fluctuations in attention and level of consciousness. In dementia, the onset is insidious and attention and level of consciousness are typically preserved until the advanced phase. ^[15]

Other ^[16]

• Hydrocephalus (e.g., normal pressure hydrocephalus)
• Osmotic demyelination syndrome
• Hypertensive encephalopathy
• Herpes encephalitis
• Chronic subdural hematoma
• Other causes of altered mental status

The differential diagnoses listed here are not exhaustive.

General principles

For the approach to undifferentiated patients with altered mental status, see “Initial management of AMS.”

• Treatment of the underlying condition: the mainstay of management
  • Consider discontinuing; or reducing the dose of causative medications, e.g., anticholinergics. ^[7][10]
  • See “Etiology” for a detailed list of conditions.
• Supportive care: Clinical manifestations, functional limitations, and associated risks of delirium can persist, requiring admission and supportive care.
• Behavioral emergencies: See “Treatment of agitation in delirium.”

Do not discharge patients from ambulatory settings unless delirium resolves with initial management and an underlying cause has been identified and treated. ^[17]

In patients requiring admission, consider a higher level of care based on clinical status and monitoring needs.

Supportive care ^[7][10][16]

• Patient comfort and symptom control
  • Fever control and pain management (preferably with nonopioid medications) ^[10]
  • Maintain adequate hydration and nutrition (see “IV fluid therapy”).
  • Evaluate and treat urinary retention or fecal impaction if present.
  • Mobilize the patient as soon as possible.
• Reducing confusion
  • Reorient the patient to time, place, and person ^[7]
  • Initiate cognitive stimulation therapy to improve cognitive function.
  • See also “Prevention.”
• Prevention of complications ^[7]
  • Prevention of decubitus ulcers (e.g., mobilization, toilet program)
  • Aspiration precautions
  • Fall prevention
  • Minimize the use of physical restraints.

A comprehensive care strategy involving multidisciplinary health providers and family members is preferred to prevent and address complications of delirium. ^[7]

Patients with delirium may become agitated or aggressive as a result of acute confusion, particularly in unfamiliar environments.

• For agitation in patients with dementia, see “Management of dementia.”
• For more comprehensive management, see also “Management of the agitated patient.”

Nonpharmacological measures

Agitation should initially be managed with nonpharmacologic strategies.

• Continue supportive care (e.g., reassurance, reorientation).
• Arrange for a family member or sitter to remain with the patient at all times.
• Identify and treat easily reversible causes of agitation: e.g., dehydration, hunger, pain, hypoxia, or urinary retention.
• Use de-escalation techniques: e.g., calm verbal interaction, clear communication. ^[18]

Avoid physical restraints as much as possible in older patients with delirium, as they can worsen distress and agitation, as well as contribute to preventable injuries. ^[19]

Pharmacotherapy ^[7]

Medications should be reserved for refractory agitation.

• Sedating medications should be limited to patients with agitation severe enough to pose a risk to themselves or others.
• To minimize the risk of worsening delirium with medication:
  • Check for drug interactions.
  • Start with the lowest possible dose.
  • Titrate until agitation reduces.
  • Discontinue the drug as soon as possible.
• Consider specialist consultation (e.g., psychiatry, geriatrics) for patients who need continual dosing.
• The recommended dosages for older adults are lower than for younger patients. ^[7][20]

Antipsychotics ^[7][20]

• Agents
  • Typical antipsychotics: e.g., haloperidol (most commonly used) ^[20]
  • Atypical antipsychotic options ^[20];
    • Risperidone
    • Olanzapine
• Adverse effects
  • Sedation
  • Increased risk of falls
  • Extrapyramidal symptoms
  • Lowered seizure threshold

Avoid antipsychotics in patients with underlying alcohol withdrawal or benzodiazepine withdrawal (due to the risk of seizures) and in patients at high risk for QTc prolongation (due to the risk of torsades de pointes). ^[9]

Benzodiazepines ^[7][10][20]

• Clinical applications: Reserve for patients with alcohol or benzodiazepine withdrawal, or a history of neuroleptic malignant syndrome. ^[10]
• Preferred agent: lorazepam
• Adverse effects
  • Prolonged or worsening delirium
  • Oversedation and falls

Benzodiazepines are deliriogenic. Do not treat delirious patients with benzodiazepines unless the delirium is due to alcohol or benzodiazepine withdrawal.

Over one-third of cases of delirium can be prevented with nonpharmacological strategies. ^[5]

• The following measures can reduce morbidity: ^[21]
  • Early identification of at-risk patients (see “Etiology”)
  • Regular screening to detect early signs of delirium
  • Tailored care according to risk, e.g., validated monitoring tools and prevention strategies for older patients ^[9][10][21]
• Delirium is very common in the ICU; see “Supportive care in the ICU” for additional considerations. ^[22]

Older patients are at particularly high risk for delirium during hospitalization and benefit from specialized monitoring and prevention. ^[21]

Prevention strategies

• Nonpharmacologic prophylaxis
  • Reduce exposure to modifiable risk factors.
    • Avoid drugs that can worsen delirium (e.g., benzodiazepines, anticholinergics, opioids).
    • Avoid restraints if possible.
    • Ensure that the patient is comfortable and that symptoms are well controlled (see “Supportive care” in “Management” section).
  • Reorient the patient regularly.
    • Keep a clock and/or calendar near the patient to help with orientation.
    • Provide visual and hearing aids for patients with impairments.
    • Keep curtains open and lights on during daytime hours.
  • At night, reduce the amount of noise, procedures, and medication administration.
    • Disorientation may be worse if the patient is awoken at night.
    • Uninterrupted sleep is important for both prevention and management of delirium.
    • See also “Inpatient management of insomnia.”
  • Arrange for regular visits from family and friends.
  • Regularly assess at-risk patients using the CAM tool to detect delirium early.
• Pharmacological prophylaxis: Some medications (e.g., dexmedetomidine, melatonin) have been used to prevent delirium in the critical care/postoperative settings, but benefits are still uncertain. ^[16]

Uninterrupted sleep is particularly important in patients with delirium, who may experience a worsening of neuropsychiatric symptoms in the evening and at night known as sundowning.

Cholinesterase inhibitors have not been shown to be effective in the prevention or treatment of delirium. However, patients requiring long-term treatment cholinesterase inhibitors can continue to use them. ^[23][24]

• Assess the patient using the confusion assessment method (CAM) or CAM-ICU if they are critically ill.
• Identify and treat reversible precipitating causes and contributing factors.
• Perform basic diagnostic studies (e.g., POC glucose, BMP, CBC, urinalysis, ECG).
• Perform further diagnostics based on clinical suspicion (e.g., EEG, CT head).
• Review the patient's medication for possible contributing drugs or withdrawal (e.g., benzodiazepines).
• Prioritize nonpharmacological supportive care and delirium prevention strategies.
• Identify and treat easily reversible causes (e.g., pain, urinary retention).
• Use de-escalation techniques when feasible.
• Consider pharmacological treatment for refractory agitation that compromises the safety of the patient or others.
• Consider admission for further workup and management.