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. 
- A pathobiological process in the brain that:
- Can be further specified according to the suspected underlying mechanism, e.g., acute toxic-metabolic encephalopathy
- The exact mechanism responsible for delirium is unknown. 
- Pediatric, elderly (> 65 years), and hospitalized patients are particularly susceptible.
- Typically secondary to:
- Metabolic diseases (most common cause; also referred to as metabolic encephalopathy)
- 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)
- Benzodiazepines, barbiturates
- Antidepressants and antipsychotics (especially those with anticholinergic activity, e.g., quetiapine)
- Antihistamines (particularly in elderly patients)
- 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:
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:
- 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:
|Psychomotor activity||Patient groups|
|Mixed type delirium||Fluctuates or stays at baseline||Most common type in the general population|
|Hypoactive delirium||Decreased||Most common type in the elderly population|
|Hyperactive delirium||Increased (agitation)||Usually seen in delirium due to substance use or substance withdrawal|
Diagnostic criteria 
|Confusion assessment method (CAM) |
|Feature 1|| |
|Feature 2|| || |
|Feature 3|| |
|Feature 4|| || |
Diagnosis of delirium requires features 1 and 2 PLUS either feature 3 or 4.
DSM-5 diagnostic criteria for delirium
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:
Routine laboratory studies 
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
- 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.
|Symptom-based diagnostic workup for delirium|
|Suspected underlying process||Concerning features||Diagnostic studies|
|Nutritional (e.g., vitamin deficiencies)|
|Toxic (e.g., intoxication or withdrawal)|
|Psychiatric || |
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. 
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.
Delirium is most often confused with dementia. However, there are significant differences in the presentation of diseases.
|Delirium vs. dementia|
|Onset|| || |
|Course|| || |
|Level of consciousness|| || |
|Attention|| || |
|Memory|| || |
|Thought process|| || |
|Hallucinations|| || |
|Psychomotor activity|| || |
|EEG|| || |
|Reversibility|| || |
Other differential diagnoses 
The differential diagnoses listed here are not exhaustive.
Treatment of the underlying condition: the mainstay of management
- Consider discontinuing; or reducing the dose of causative medications, e.g., anticholinergics. 
- 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 
- Patient comfort and symptom control
- At least three times daily, hospital staff or family should reorient the patient to time, place, and person. 
- Initiate cognitive stimulation therapy to improve cognitive function.
- See also “Nonpharmacologic prophylaxis” in “Prevention.”
Prevention of complications 
- 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.
- Decubitus ulcers
A comprehensive care strategy involving multidisciplinary health providers and family members is preferred to prevent and address complications of delirium. 
- 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.
- 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 : e.g., calm verbal interaction, clear communication. 
- 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:
- 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. 
Antipsychotics (first-line) 
- Adverse effects
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). 
Benzodiazepines (second-line) 
- Clinical applications: Reserve for patients with alcohol or benzodiazepine withdrawal, or a history of neuroleptic malignant syndrome. 
- Preferred agent: lorazepam
- Prolonged or worsening delirium
- Oversedation and falls
- Over one-third of cases of delirium can be prevented with nonpharmacological strategies. 
- The following measures can reduce morbidity: 
- 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 
Elderly patients are at particularly high risk for delirium during hospitalization and benefit from specialized monitoring and prevention. 
- Reduce exposure to modifiable risk factors.
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.
- 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. 
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. 
- 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
- Consider pharmacological treatment for refractory agitation that compromises the safety of the patient or others.