Delirium

See Also

Epidemiology
Incidence

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

Definitions
Delirium

Delirium (Acute Encephalopathy) is an Acute Confusional State
Develops over hours to days
1. Contrast to Dementia with onset over months to years
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
Inattention, disorganized thinking and altered level of consciosness
1. Contrast to Dementia in which attention and long-term memory are typically preserved

Types
Psychomotor

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
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
Mixed Delirium
1. Mixed hyperactive and hypoactive features

Risk Factors

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

Precautions

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

Causes
Precipitating Factors

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
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
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
Illicit Substances
1. See Unknown Ingestion
2. Substance Intoxication
3. Substance Withdrawal
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
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
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
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

Causes
Life Threatening Delirium (Mnemonic - "WHHHHIMPS")

Wernicke Encephalopathy or Alcohol Withdrawal
Hypoxia or hypercarbia
Hypoglycemia
Hypertensive Encephalopathy
Hyperthermia or Hypothermia
Intracerebral Hemorrhage
Meningitis or Encephalitis
Poisoning (or iatrogenic medication induced)
Status Epilepticus

History

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

Exam

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

Signs

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)
Disorganized Thought Processes
Memory Impairment (especially short term)
Perceptual disturbances
1. Persecutory Delusions are common
2. Visual Hallucinations rare except in organic cause
Emotional lability
Motor changes
1. Myoclonus
2. Asterixis

Labs
Initial

See Altered Level of Consciousness (includes labs)
All patients
1. Comprehensive metabolic panel (Electrolytes, Liver Function Tests, Renal Function tests)
2. Complete Blood Count
3. Urinalysis and Urine Culture
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

Imaging

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

Diagnostics

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

Evaluation

See Confusion Assessment Method
See Altered Level of Consciousness (includes labs)
See Richmond Agitation Sedation Scale (or RASS)
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

Evaluation
Urgent Indications

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)
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
Serious psychiatric findings
1. See Agitated Delirium
2. Escalating aggressive behavior or threats of Violence
3. Persistent danger to self or others

Diagnosis
Criteria (DSM-5 Criteria)

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
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)
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
References
1. (2013) DSM-5, APA

Differential Diagnosis

Management
General

See Agitated Delirium
1. Emergent management to emergently de-escalate risk to patient and staff
See Agitation in Dementia
1. Provides a similar approach as for Agitated Delirium (esp. non-medication management)
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
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

Management
Antipsychotics

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
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)
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

Management
Benzodiazepines

Use with caution
1. May paradoxically exacerbate Agitation (esp. elderly)
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
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)

Management
Other Medications

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]
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

Prognosis

Delirium is reversible in up to 80% of cases
1. Evaluation for underlying cause is critical in resolution
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)

Prevention

Optimize hydration and nutrition
Early mobilization of patients
Reduce restraints and catheters
Reorient patient frequently (involve family presence)
Correct Vision (glasses) and Hearing (Hearing Aids)
Manage comorbidities
1. Manage pain
2. Optimize adequate Oxygen Saturation
Manage Insomnia
1. See Insomnia Management
2. See Sleep Hygiene
3. Avoid Sedatives for sleep
Avoid psychoactive and Anticholinergic Medications

Resources

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

References

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