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 elderly patients and is typically secondary to another medical condition or polypharmacy. 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)
• Subsyndromal delirium: proposed term for patients with clinical features of delirium that do not fulfill the criteria for a delirium diagnosis. ^[1]
• Acute encephalopathy
  • 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

References: ^[1][2]

• The exact mechanism responsible for delirium is unknown. ^[3][4][5]
• Pediatric, elderly (> 65 years), and hospitalized patients are particularly susceptible.
• Typically secondary to:
  • Metabolic diseases (most common cause; also referred to as metabolic encephalopathy)
    • 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 such as UTIs (most common cause in elderly patients), pneumonia, meningitis
  • Trauma (e.g., hip fracture, head injury)
  • CNS pathology (e.g., stroke, brain tumor)
  • Hypoxia (e.g., anemia, cardiac failure, COPD, pulmonary embolism)
  • Acute cardiovascular disease (MI, shock, vasculitis)
  • Drugs and toxins (also referred to as toxic encephalopathy)
    • Anticholinergics
    • Benzodiazepines, barbiturates
    • Antidepressants and antipsychotics (especially those with anticholinergic activity, e.g., quetiapine)
    • Antihistamines (particularly in elderly patients)
    • Opioids
    • Diuretics (may cause electrolyte abnormalities)
    • Recreational drugs (intoxication/withdrawal)
    • Alcohol use disorder and alcohol withdrawal
    • Heavy metals (e.g., arsenic, lead, mercury)
  • Sleep deprivation
  • Major surgery
  • Hearing or vision loss
  • Ongoing symptoms, including:
    • Constipation
    • Urinary retention
    • Pain
    • Dehydration

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]

Routine laboratory studies ^[8][10]

The following studies are recommended in all patients with a new presumptive delirium diagnosis. Depending on the underlying etiology, the results may be normal.

• Complete blood count
  • Low Hb
  • WBC: may be elevated or low in infection
• BMP
  • Serum glucose: hypoglycemia or hyperglycemia
  • Urea and creatinine: elevated in renal failure and uremia.
  • Electrolytes: elevated or low potassium, sodium, or calcium ^[11]
• Magnesium: elevated or low
• Liver chemistries: altered in liver failure or toxicity
• Urinalysis: abnormalities related to UTI (e.g., pyuria, bacteriuria) or renal failure (e.g., urinary casts)

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. ^[8]

The symptoms of delirium overlap with a number of other neurological disorders; 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.

Other differential diagnoses ^[16]

• Hydrocephalus (e.g., normal pressure hydrocephalus)
• Osmotic demyelination syndrome
• Hypertensive encephalopathy
• Herpes encephalitis
• Chronic subdural hematoma

The differential diagnoses listed here are not exhaustive.

General principles

• Treatment of the underlying condition: the mainstay of management
  • Consider discontinuing; or reducing the dose of causative medications, e.g., anticholinergics. ^[8][10]
  • See “Etiology” for a detailed list of conditions.
• Ongoing 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.”

Supportive care ^[8][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.
  • Physical and occupational therapy to mobilize the patient as soon as possible.
• Reducing confusion
  • At least three times daily, hospital staff or family should reorient the patient to time, place, and person. ^[8]
  • Initiate cognitive stimulation therapy to improve cognitive function.
  • See also “Nonpharmacologic prophylaxis” in “Prevention.”
• Prevention of complications ^[8]
  • Decubitus ulcers
    • Mobilize hypoactive patients frequently (i.e., every 2 hours).
    • Establish a toilet program to help manage incontinence.
  • Aspiration of food or fluid
    • Elevate the head of the bed.
    • Supervise meals and use assisted feeding techniques.
  • Falls and injuries
    • Mobilize patients with assistance.
    • 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. ^[8]

• Patients with delirium may become agitated or aggressive as a result of acute confusion, particularly in unfamiliar environments.
• Agitation should initially be managed with nonpharmacologic strategies.
• Medications should be reserved for refractory agitation.

Nonpharmacological measures

• 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. ^[17]

Avoid physical restraints as much as possible in elderly patients with delirium, as they can worsen distress and agitation, as well as contribute to preventable injuries. ^[18]

Pharmacotherapy^[8]

• 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. ^[8][19]

Antipsychotics (first-line) ^[8][19]

All antipsychotics have sedating properties that may help treat refractory agitation.

• Agents
  • Typical antipsychotics: e.g., haloperidol (most commonly used) ^[19]
  • Atypical antipsychotic options ^[19]
    • Risperidone
    • Olanzapine
• Adverse effects
  • 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 (second-line) ^[8][10][19]

• 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: ^[20]
  • 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 elderly patients ^[9][10][20]

Elderly patients are at particularly high risk for delirium during hospitalization and benefit from specialized monitoring and prevention. ^[20]

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.
  • 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.
  • 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. ^[21][22]

• Assess the patient with the confusion assessment method (CAM)
• 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 prevention strategies.
  • Regular reorientation, sleep hygiene, minimize unnecessary stimulation
  • Avoid physical restraints and deliriogenic drugs
  • Encourage the use of hearing and visual aids as needed.
  • Consider cognitive, occupational, and physical therapy.
  • Support family involvement and consider a sitter if needed.
  • Complication prevention (e.g., pressure ulcers, aspiration, dehydration, falls).
• Prioritize nonpharmacological measures to treat agitation
  • 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.
  • Antipsychotics are preferred (e.g., haloperidol).
  • Use benzodiazepines in alcohol or benzodiazepine withdrawal.