Delirium

Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. There are many causes of delirium. Early recognition and accurate diagnosis constitute the 1st steps to adequate management. The primary goal of treatment is to identify and reverse the underlying cause and prevent future episodes. Pharmacotherapy is reserved for the most severe cases of agitation.

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Overview

Definition

  • Delirium is defined as an acute alteration in the levels of consciousness and cognition.
  • Delirium is considered an acute neurologic emergency with increased rates of morbidity and mortality. 
  • While delirium is potentially a life-threatening condition, it is treatable and potentially reversible with early recognition and treatment.

Epidemiology

  • More prevalent in critically ill patients such as those in ICUs
  • Prevalence may be as high as 80% in mechanically ventilated patients. 
  • Prevalence is high among patients who have undergone surgical procedures (up to 50% following hip fracture repair or cardiac procedures).

Pathophysiology

  • The exact pathophysiology of delirium is unknown.
  • Several hypotheses exist to explain potential mechanisms for delirium: 
    • Neuroinflammation secondary to elevated levels of cortisol and cytokines
    • Impairments in the cholinergic pathway 
    • Neurotransmitter imbalance, specifically excess dopaminergic activity

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Etiology

Predisposing and precipitating factors

Predisposing:

  • Age > 70 years (most common) 
  • History of cognitive impairment 
  • Sleep disturbances 

Precipitating:

  • Infections
  • Adverse drug responses
  • Electrolyte disturbances

Etiology

The acronym “DELIRIUM” can be helpful in remembering the most common etiologies of the condition.

  • Drug: 
    • Multiple medications (risk increases as the number of drugs increases)
    • Intoxication or withdrawal:
      • Prescription drugs
      • Illicit drugs
      • Alcohol
    • Drug classes that can cause delirium:
      • Opiates/opioids
      • Benzodiazepines
      • Barbiturates 
    • Also includes toxins
    • Also includes drug-drug interactions
  • Environmental and emotional factors: 
    • Environmental factors:
      • Hospitalization
      • Immobilization (e.g., lack of assistive devices) 
    • Emotional factors:
      • Anxiety
      • Depression
      • Pain
  • Low oxygen:
    • Hypoxia
    • Hypercapnia 
  • Infection:
    • Pneumonia
    • Skin ulcers
    • Urinary tract infection
    • Sepsis
  • Retention:
    • Urinary retention
    • Constipation 
    • Volume overload states
  • Intracranial abnormality:
    • Seizures
    • Cerebrovascular accidents
    • Neoplasm
    • Trauma
  • Underhydration/undernutrition: 
    • Poor oral intake 
    • Chronic alcoholism
  • Metabolic: 
    • Electrolyte imbalance
    • Elevated liver enzymes
    • Elevated ammonia levels
    • Elevated kidney enzymes (uremia)
    • Thyroid hormone imbalance

Clinical Presentation

Hallmarks of delirium

  • Altered consciousness 
  • Disorientation
  • Impairment in cognitive function and memory
  • Rapid onset (within hours to days)
  • Unpredictable fluctuation of symptoms in a given day

Classification of delirium

Based on the main types of symptoms exhibited

  • Hyperactive delirium:
    • Hypervigilant and highly aroused
    • Restless
    • Agitated
    • May experience hallucinations
    • Sleep disturbances 
  • Hypoactive delirium:
    • Withdrawn, lethargic
    • Decreased levels of activity
    • Slowed thought process and speech
    • May experience hallucinations
    • Sleep disturbance 
  • Mixed delirium: a mix of features of both hyper- and hypoactive delirium

Diagnosis

History and exam

  • Delirium is usually a clinical diagnosis that is made on presentation with altered mental status.
  • Often misdiagnosed as dementia or depression
  • Owing to the patient’s confused state, it is imperative to obtain history from caregivers whenever possible.
  • A thorough physical exam including a complete neurologic exam is necessary.
  • Mental status exam and cognitive screening tests can set a baseline to document the clinical course of the patient: Confusion assessment method (CAM) can be quickly given to a caregiver or nurse to screen for delirium.

Lab studies and imaging

  • Standard studies: 
    • CBC
    • Electrolytes
    • Thyroid-stimulating hormone (TSH)
    • Vitamin B12 and folate 
    • Urinalysis
    • HIV antibodies 
    • Rapid plasma reagin 
    • Chest radiography
    • ECG
    • EEG
  • Ancillary tests: 
    • Lumbar puncture and CSF analysis 
    • Blood/urine cultures 
    • CT
    • MRI

Management

Overview

  • Mainstays of management include decreasing both predisposing and precipitating factors.
  • Any underlying causes of delirium must be found and treated. 
  • There are no FDA-approved medications for the management of delirium.

Nonpharmacologic interventions

  • Provide sensory, environmental, and physical support: 
    • Presence of family or regular patient sitter 
    • The patient’s environment must not have sensory deprivation or overload. 
  • Maintain adequate hydration and nutritional status. 
  • Prevent skin breakdown and bedsores. 
  • Physical restraints must only be used as the last resort in the case of severe agitation.

Pharmacotherapy

  • Pharmacotherapy is reserved for severe cases when a patient becomes severely agitated, placing their own or others’ safety at risk.
  • 1st-line treatment of aggression: 1st-generation antipsychotics (e.g., haloperidol) 
  • 2nd-line treatment of aggression: 2nd-generation antipsychotics (e.g., quetiapine, olanzapine) 
  • Cholinesterase inhibitors have no role in decreasing the incidence of delirium.
Table: Commonly prescribed medications for the management of delirium
Drug classIndicationsAdverse effects
1st-generation antipsychoticsSmall dosages as needed to control severe agitation
  • QTc prolongation
  • Extrapyramidal symptoms
  • Increased risk of neuroleptic malignant syndrome
2nd-generation antipsychotics
  • Small dosages as needed to control severe agitation
  • Better tolerated than 1st-generation antipsychotics
  • QTc prolongation
  • Extrapyramidal symptoms
  • Increased risk of neuroleptic malignant syndrome
Benzodiazepines
  • In cases of delirium resulting from withdrawal of sedatives or alcohol
  • When antipsychotics are contraindicated
  • Can worsen delirium
  • Can cause respiratory depression
MelatoninSmall doses at night for sleep
  • Stomach ache
  • Headache
  • Daytime sleepiness
  • Higher doses may prolong delirium.
Dexmedetomidine
  • For rapid sedation in case of aggression
  • When benzodiazepines cannot be used
  • Hypotension
  • No evidence in preventing delirium
GabapentinNonopioid pain controlSedation, peripheral edema

Prevention

  • Avoid precipitating and/or predisposing factors:
    • Minimize polypharmacy.
    • Avoid intoxicants.
    • Hydration/nutrition plan
  • Avoid sensory deprivation:
    • Provide:
      • Clocks
      • Calendars
      • Window with outside view
      • Access to personal possessions (e.g., family photos, personal keepsakes)
  • Prevention of physical and cognitive decline:
    • Regular opportunities to exercise:
      • Scheduled recreation
      • Scheduled outings
    • Regular opportunities for social interactions:
      • Allow friend/family visits
      • Communal meals
    • Availability of visual aids (glasses) and hearing aids
    • Availability of mobility-assistance devices:
      • Cane
      • Walker
      • Wheelchair
  • Sleep-hygiene and sleep-maintenance interventions:
    • Avoid sedating/mind-altering medications if possible.
    • Consistent sleep schedule
    • Provide earplugs.
  • Pro re nata sedatives for the control of acute episodes may be warranted. 
  • Management of underlying chronic disease states
  • Pain management (opiates/opioids as the last resort)

Differential Diagnosis

  • Dementia: major neurocognitive disorders (NCDs), also known as dementia, are a group of diseases characterized by a progressive and persistent decline in a person’s memory and executive function. Dementia is the leading cause of disability worldwide among the elderly. There are several distinct etiologies for major NCDs. Delirium can be differentiated from dementia by its rapid onset and altered consciousness levels. 
  • Sundowning: worsening of cognition and orientation in patients during the evening and at night. Sundowning is common among people with major NCDs. While there is no clear etiology, there are poor outcomes, such as hospitalization, hastening of cognitive decline, and increased caregiver burden, associated with sundowning. The history of symptoms specifically worsening at night and improving during the day distinguishes sundowning from delirium; however, a clinical workup is necessary to rule out delirium. 
  • Schizophrenia: a psychotic disorder characterized by positive symptoms (delusions, hallucinations, and disorganized speech or behavior) and negative symptoms (flat affect, avolition, anhedonia, poor attention, and alogia). Schizophrenia is associated with a decline in function lasting > 6 months. While periods of agitation are common in delirium, patients with schizophrenia do not exhibit changes in their orientation or alertness. New onset of schizophrenia in the typical demographic that fits delirium is also extremely unlikely.

References

  1. Kennedy, M. (2018). Delirium in the emergency department: Diagnosis, evaluation, and management. DeckerMed Medicine. Retrieved July 6, 2021, from https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.16437
  2. Sadock, B.J., Sadock, V.A., Ruiz, P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 21, Neurocognitive disorders, pages 697–704. Philadelphia, PA: Lippincott Williams and Wilkins.
  3. Francis, J. (2019). Delirium and acute confusional states: Prevention, treatment, and prognosis. UpToDate. Retrieved July 9, 2021, from https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis 
  4. Echeverría, MdL. R., Paul, M. Delirium. [Updated 2020 Nov 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. https://www.ncbi.nlm.nih.gov/books/NBK470399/
  5. Lange, P.W., Lamanna, M., Watson, R., Maier, A.B. (2019). Undiagnosed delirium is frequent and difficult to predict: Results from a prevalence survey of a tertiary hospital. Journal of Clinical Nursing, 28, 2537–2542. https://doi.org/10.1111/jocn.14833

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