Delirium

Aka: Delirium, Acute Encephalopathy

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II. Epidemiology: Incidence

  1. Older, hospitalized adults: 30%
  2. Older surgical patients: 10-50% (varies based on Frailty and procedure complexity)
    1. Dyer (1995) Arch Intern Med 155:461-5 [PubMed]
  3. Intensive Care unit: 70%
    1. McNicoll 2003 J Am Geriatr Soc 51:591-8 [PubMed]
  4. Emergency department: 10%
    1. Elie 2000 CMAJ 163:977-81 [PubMed]

III. Definitions: Delirium

  1. Delirium (Acute Encephalopathy) is an Acute Confusional State
  2. Develops over hours to days
    1. Contrast to Dementia with onset over months to years
  3. Waxes and wanes and is reversible
    1. Contrast to Dementia with a constant, progressive course (with minor fluctuations) and irreversible
    2. Lewy Body Dementia, as an exception, may present with fluctuations
  4. Inattention, disorganized thinking and altered level of consciosness
    1. Contrast to Dementia in which attention and long-term memory are typically preserved

IV. Types: Psychomotor

  1. Hypoactive Delirium
    1. Most common in the elderly and most commonly under-recognized and missed
    2. Presents with at least 4 criteria
      1. Unawareness, decreased alertness or lethargy
      2. Sparse or slow speech, slow movements or staring
  2. Hyperactive Delirium
    1. See Agitated Delirium
    2. Less common in the elderly
    3. Presents with at least 3 criteria
      1. Hypervigilance, restlessness or anxiousness
      2. Fast or loud speech or swearing
      3. Irritability, impatience, combativeness, Agitation, anger or uncooperative
      4. Singing, laughing, euphoria
      5. Fast motor responses or easy startling
      6. Distractability, Tangentiality, persistent thoughts or Nightmares
  3. Mixed Delirium
    1. Mixed hyperactive and hypoactive features

V. Risk Factors

  1. General
    1. Age over 65 years (esp. male gender)
    2. Poor nutritional status
    3. Poor functional status
    4. Insomnia or other sleep deprivation
  2. Underlying neurologic or psychiatric disorder
    1. Underlying Dementia
    2. Preexisting Major Depression
  3. Sensory Deficits
    1. Hearing Loss
    2. Decreased Visual Acuity
  4. Substance Use Disorder
    1. Alcohol Abuse and Alcohol Withdrawal
    2. Drug Abuse
    3. Prior brain injury (vascular or Traumatic Injury)
  5. Iatrogenic
    1. Polypharmacy
    2. Hospitalization or post-surgery
    3. More than 3 medications added within 24 hours
  6. Multiple comorbid conditions
    1. Hepatic failure
    2. Chronic Renal Failure (esp. Hemodialysis dependent)
    3. Chronic Pain

VI. Precautions

  1. Delirium is high risk for morbidity and mortality (see prognosis below)
  2. Patients with Delirium are at high risk for injury to themselves and others
  3. Evaluation for underlying cause is critical to resolution and complication prevention

VII. Causes: Precipitating Factors

  1. Infectious (precipitates 50% of Delirium cases in elderly)
    1. Precautions: Elderly with infectious causes
      1. Fever is absent in up to 20-30% of elderly patients with bacteremia
      2. Cough and fever are absent in 65% of elderly with Pneumonia
      3. Abdominal tenderness is absent in 65% of elderly with intra-abdominal infections
      4. Adedipe (2006) Emerg Med Clin North Am 24(2): 433-48 [PubMed]
    2. Pneumonia
    3. Urinary Tract Infection
    4. Intraabdominal infection
    5. Soft tissue infection (e.g. Pressure Ulcers)
    6. Meningitis or Encephalitis
  2. Cardiopulmonary
    1. Myocardial Infarction (esp. elderly women and diabetics)
    2. Congestive Heart Failure
    3. Cerebrovascular Accident
    4. Dehydration, Hemorrhage or other shock state
    5. Hypoxia
    6. Hypercarbia
  3. Medications
    1. See Medications to Avoid in Older Adults
    2. See Medication Causes of Delirium in the Elderly
    3. See Polypharmacy
    4. Serotonin Syndrome
    5. Psychoactive medications
    6. Anticholinergic Medications
    7. Opioids
    8. Benzodiazepines
  4. Illicit Substances
    1. See Unknown Ingestion
    2. Substance Intoxication
    3. Substance Withdrawal
  5. Endocrine and Metabolic
    1. Electrolyte abnormalities (e.g. Hypercalcemia)
    2. Acute Hepatic Failure (Hepatic Encephalopathy)
    3. Acute Renal Failure (Uremic encephalopathy)
    4. Hypoglycemia or Hyperglycemia
    5. Thiamine deficiency (e.g. Wernicke Encephalopathy)
    6. Hypothyroidism or Hyperthyroidism
  6. Neuropsychiatric
    1. Cerebrovascular Accident
    2. Sleep deprivation
    3. Seizure
    4. CNS Hemorrhage (Subarachnoid Hemorrhage, Subdural Hematoma, Epidural Hematoma)
    5. CNS Neoplasm
    6. Closed Head Injury
  7. Iatrogenic
    1. Physical Restraints
    2. Indwelling Urinary Catheter
    3. Other tethers (e.g. telemetry monitoring wires, catheters)
    4. Medical procedures
      1. Postoperative State: 15 to 53% of elderly patients
      2. Hip Fracture: 28-61% of elderly patients
    5. Intensive Care setting
      1. ICU with Mechanical Ventilation: 60-80% of elderly patients
      2. ICU without Mechanical Ventilation: 20-50% of elderly patients
  8. Miscellaneous
    1. Hypothermia or hyperthermia (e.g. Heat Stroke)
    2. Toxin Induced Neurologic Changes
    3. Burn Injury
    4. Trauma (e.g. major Fracture)
    5. Urine retention
    6. Stool retention, Constipation or Fecal Impaction

VIII. Causes: Life Threatening Delirium (Mnemonic - "WHHHHIMPS")

  1. Wernicke Encephalopathy or Alcohol Withdrawal
  2. Hypoxia or hypercarbia
  3. Hypoglycemia
  4. Hypertensive Encephalopathy
  5. Hyperthermia or Hypothermia
  6. Intracerebral Hemorrhage
  7. Meningitis or Encephalitis
  8. Poisoning (or iatrogenic medication induced)
  9. Status Epilepticus

IX. History

  1. Obtain history from family or Caregiver
  2. Evaluate risk factors and causes as listed above
  3. Home Medications
    1. All bottles of currently taken medications should be brought to evaluation
  4. Substance use
    1. Alcohol Abuse
    2. Benzodiazepine use

X. Exam

  1. Review Vital Signs
    1. See Toxin Induced Vital Sign Changes
  2. Neurologic Exam
    1. Careful and complete Neurologic Exam
  3. Abdomen, Pelvis and Rectum
    1. Occult abdominal infection (e.g. Diverticulitis, Appendicitis)
    2. Perirectal Abscess
  4. Skin Exam
    1. Infected Decubitus Ulcer
  5. Focus areas for cause
    1. Hypoxia
    2. Dehydration
    3. Infection
    4. Uncontrolled pain

XI. Signs

  1. Fluctuating levels of consciousness
    1. Inattention
      1. The cornerstone of Delirium
      2. Unable to count backwards from 20 or name months or weekdays backwards
    2. Perseveration
    3. Decreased alertness
    4. Disorientation
    5. Extremes of activity (Somnolence to Agitation)
  2. Disorganized Thought Processes
  3. Memory Impairment (especially short term)
  4. Perceptual disturbances
    1. Persecutory Delusions are common
    2. Visual Hallucinations rare except in organic cause
  5. Emotional lability
  6. Motor changes
    1. Myoclonus
    2. Asterixis

XII. Labs: Initial

  1. See Altered Level of Consciousness (includes labs)
  2. All patients
    1. Comprehensive metabolic panel (Electrolytes, Liver Function Tests, Renal Function tests)
    2. Complete Blood Count
    3. Urinalysis and Urine Culture
  3. Other labs to consider
    1. Thyroid Function Tests
    2. Vitamin B12
    3. Venous Blood Gas or Arterial Blood Gas
    4. Blood Alcohol Level
    5. Urine Drug Screen
    6. Acetaminophen level
    7. Salicylate level
    8. Serum Ammonia
    9. Lactic Acid
    10. Medication levels (e.g. serum Lithium level or anticonvulsant level)
    11. C-Reactive Protein (CRP) or Erythrocyte Sedimentation Rate (ESR)
    12. Lumbar Puncture

XIII. Imaging

  1. Chest XRay
    1. Evaluate for occult Pneumonia
  2. CT Head Indications
    1. Focal neurologic deficit
    2. Altered Level of Consciousness
    3. Recent Head Trauma
    4. Fever with encephalopathy
  3. MRI Brain Indications
    1. Persistent Delirium without obvious cause

XIV. Diagnostics

  1. Electrocardiogram
    1. Exclude QTc Prolongation and QRS Widening
  2. Electroencephalogram
    1. Diffuse slow waves

XV. Evaluation

  1. See Confusion Assessment Method
  2. See Altered Level of Consciousness (includes labs)
  3. See Richmond Agitation Sedation Scale (or RASS)
  4. Focus areas
    1. Key to evaluation is identifying underlying Delirium cause
    2. Carefully review medication list and possible ingestions
    3. Identify sources of infection including a full skin exam
    4. Identify focal neurologic deficits
    5. Identify subtle signs of Trauma

XVI. Evaluation: Urgent Indications

  1. Dramatic Vital Sign change (with associated signs or symptoms)
    1. Systolic Blood Pressure <90 mmHg
    2. Heart Rate <50/min or >120/min
    3. Respirations >30/min
    4. Temperature <96 F (36 C) or >101 F (38 C)
  2. Serious findings suggestive of underlying cause
    1. New focal deficits
    2. New respiratory distress (e.g. Hypoxia, Dyspnea)
    3. Cerebrovascular Accident
    4. Chest Pain
    5. Hematuria
  3. Serious psychiatric findings
    1. See Agitated Delirium
    2. Escalating aggressive behavior or threats of Violence
    3. Persistent danger to self or others

XVII. Diagnosis: Criteria (DSM-5 Criteria)

  1. Key criteria (all 4 must be present)
    1. Disturbed awareness and attention
      1. Altered Level of Consciousness
      2. Altered content (e.g. inattention, lost focus)
    2. Altered cognition or Perception from baseline
      1. Decreased short-term memory, disturbed language or Perception (Hallucinations, Delusions)
      2. Not due to pre-existing Dementia (or related fluctuations such as sun downing)
    3. Short duration of symptom onset (Hours to days)
      1. Rapid deterioration in all higher cortical functions
      2. Mental status fluctuates widely throughout the day
    4. History, exam or labs suggests medical cause, Intoxication or medication side effect
  2. Other factors may be associated
    1. Psychomotor behavioral disturbance (e.g. change in activity, sleep)
    2. Emotional disturbance (e.g. fear, depression, euphoria)
    3. Autonomic Instability (Abnormal Vital Signs)
  3. Clinical Subtypes (see Types above)
    1. Hyperactive Delirium
      1. Increased arousal, restlessness or Agitation
      2. Hallucinations
      3. Inappropriate behavior
    2. Hypoactive Delirium
      1. Lethargy or reduced motor activity
      2. Incoherent speech
      3. Lack of interest
    3. Mixed Delirium
  4. References
    1. (2013) DSM-5, APA

XVIII. Differential Diagnosis

  1. See Altered Level of Consciousness Causes
  2. Dementia
  3. Psychosis
  4. Major Depression

XIX. Management: General

  1. See Agitated Delirium
    1. Emergent management to emergently de-escalate risk to patient and staff
  2. See Agitation in Dementia
    1. Provides a similar approach as for Agitated Delirium (esp. non-medication management)
  3. Non-pharmacologic calming techniques are preferred
    1. Provide a quiet, non-activating environment
    2. Limit probes, beeping monitors, automatic Blood Pressure cuffs, bright lights
    3. Limit multiple intravenous lines, nasal oxygen, Bladder catheters
    4. Avoid Physical Restraints if at all possible
  4. Admission for Delirium is generally warranted
    1. Exception: Mild or resolved Delirium symptoms with reliable family and safe environment
      1. Discharge to home with close supervision and closer interval follow-up
    2. Consider geriatric unit admission if available for Delirium in elderly patients

XX. Management: Antipsychotics

  1. Precautions
    1. Antipsychotics are associated with increased mortality in the elderly
    2. Avoid in Parkinsonism due to high risk of Extrapyramidal Side Effects
    3. Use only short-term and only when non-pharmacologic measures fail
    4. Limit to monitored settings
    5. See each agent for contraindications and adverse effects before use
  2. First Generation Antipsychotics
    1. Haloperidol 0.25 to 0.5 mg PO or IM every 4 hours (or 0.5 to 1.0 mg every 6 hours, maximum 30 mg/day)
  3. Second Generation Antipsychotics
    1. Risperidone (Risperdal)
      1. Adult: 0.5 mg orally twice daily (max: 6 mg/day)
      2. Decrease dose in reduced Creatinine Clearance
      3. More commonly used Antipsychotic in the elderly
    2. Olanzapine (Zyprexa)
      1. Adult: 5 to 10 mg orally twice daily (maximum 20 mg/day)
      2. Elderly: 2.5 to 5 mg orally twice daily
      3. Parenteral: 5 to 10 mg IM every 12 hours (maximum 30 mg/day)
      4. Commonly used Antipsychotic in U.S. emergency departments
    3. Quetiapine (Seroquel)
      1. Adult: Start 25 mg orally twice daily or 50 mg at bedtime (maximum 150 mg/day)
      2. Elderly: Start 12.5 mg orally twice daily (or 25 mg at bedtime)
      3. Preferred in Lewy Body Dementia and Parkinsonism
    4. Ziprasidone (Geodon)
      1. Adult: 20 to 40 mg orally twice daily with meals (maximum 80 mg/day)
      2. Parenteral: 5 to 10 mg IM (maximum 40 mg/day)
    5. Aripiprazole (Abilify)
      1. Dose: 2 to 5 mg orally once daily (maximum 15 mg/day)
      2. Less risk of QTc Prolongation than the other Antipsychotics

XXI. Management: Benzodiazepines

  1. Use with caution
    1. May paradoxically exacerbate Agitation (esp. elderly)
  2. Indications
    1. Parkinsonism (in which Antipsychotics are avoided if possible due to Extrapyramidal Side Effects)
    2. Drug Withdrawal or Alcohol Withdrawal
    3. Neuroleptic Malignant Syndrome
  3. Preparations
    1. Lorazepam (Ativan) 0.5 to 1 mg orally or IV every 4 hours as needed
    2. Midazolam (Versed) 2.5 to 5 mg IM or IV (maximum 20 mg/day)
      1. Rapid IM onset and preferred parenteral Benzodiazepine for IM use (when IV Access is unavailable)

XXII. Management: Other Medications

  1. Hypoactive Delirium
    1. No strong evidence for any medication intervention
    2. Medications that may be considered
      1. Aripiprazole
      2. Methylphenidate
    3. References
      1. Lodewijckx (2021) J Am Med Dir Assoc 22(6): 1313-6 [PubMed]
  2. End-Of-Life Care
    1. See Mental Status Changes Near End of Life
    2. Delirium is common near end of life (88% of patients on inpatient Hospice)
    3. Preferred agents
      1. Methadone
      2. Short acting Benzodiazepines (e.g. Midazolam, Lorazepam)
      3. Consider Haloperidol
    4. References
      1. Hui (2017) JAMA 318(11): 1047-56 [PubMed]
      2. Hui (2018) Curr Opin Support Palliat Care 12(4): 489-94 [PubMed]
      3. Moryl (2005) Palliat Support Care 3(4): 311-7 [PubMed]

XXIII. Prognosis

  1. Delirium is reversible in up to 80% of cases
    1. Evaluation for underlying cause is critical in resolution
  2. Delirium associated mortality is very high
    1. Inpatient mortality is as high as 25 to 39%
    2. Prolonged Delirium increases risk 3 fold for death within one year (compared with rapidly resolving Delirium)

XXIV. Prevention

  1. Optimize hydration and nutrition
  2. Early mobilization of patients
  3. Reduce restraints and catheters
  4. Reorient patient frequently (involve family presence)
  5. Correct Vision (glasses) and Hearing (Hearing Aids)
  6. Manage comorbidities
    1. Manage pain
    2. Optimize adequate Oxygen Saturation
  7. Manage Insomnia
    1. See Insomnia Management
    2. See Sleep Hygiene
    3. Avoid Sedatives for sleep
  8. Avoid psychoactive and Anticholinergic Medications
    1. See Medications to Avoid in Older Adults (STOPP, Beers' Criteria)
    2. Anticholinergic Medications
    3. Benzodiazepines
    4. Opioids

XXV. Resources

  1. Delirium and acute problematic behavior in the long-term care setting
    1. http://www.guideline.gov/content.aspx?id=12379

XXVI. References

  1. Ho Han (2013) Crit Dec Emerg Med 27(11): 11-23
  2. Khoujah and Magidson (2016) Crit Dec Emerg Med 30(10): 3-10 -Cole (2004) Am J Geriatr Psychiatry 12(1):7-21
  3. Inouye (2006) N Engl J Med 354(11): 1157-65 [PubMed]
  4. Jaqua (2023) Am Fam Physician 108(3): 278-87 [PubMed]
  5. Kalish (2014) Am Fam Physician 90(3): 150-8 [PubMed]
  6. Miller (2008) Am Fam Physician 78(11): 1265-70 [PubMed]

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