Neurology · PANCE / PANRE

Delirium

Acute, fluctuating disturbance of attention and awareness from an underlying medical cause.

Also known as: delirium, acute confusional state, encephalopathy, ICU delirium, sundowning

Overview

Acute, fluctuating disturbance of attention, awareness, and cognition that develops over hours to days, caused by an underlying medical condition, substance, or medication, and not better explained by a pre-existing or evolving neurocognitive disorder.

Epidemiology

Affects 15-25% of hospitalized older adults on general wards, up to 50% post-operatively, and 70-87% of ICU patients. Associated with prolonged hospitalization, functional decline, increased mortality, and persistent cognitive impairment.

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Risk factors

Predisposing: advanced age, baseline dementia or cognitive impairment, sensory impairment (visual, hearing), frailty, multiple comorbidities, polypharmacy, prior delirium, depression, alcohol misuse, malnutrition
Precipitating: acute infection (UTI, pneumonia, sepsis), metabolic derangements (Na, glucose, calcium, uremia, hepatic failure, hypoxia), medications (anticholinergics, benzodiazepines, opioids, corticosteroids), substance intoxication/withdrawal, surgery and anesthesia, restraints, urinary catheters, sleep deprivation, ICU environment, pain, dehydration, stroke, hypoxia, MI, fecal impaction, urinary retention

Pathophysiology

Multifactorial: neurotransmitter imbalance (cholinergic deficit, dopaminergic excess), neuroinflammation (cytokine surge crossing the blood-brain barrier), oxidative stress, and disruption of neural network connectivity (particularly prefrontal-thalamic and default mode networks). Prefrontal and posterior parietal dysfunction underlies attentional deficits.

Clinical presentation

Symptoms

Acute onset (hours to days) with fluctuating course (often worse at night — 'sundowning')
Disturbance of attention (cannot focus, sustain, or shift attention) and awareness (reduced orientation to environment)
Disorganized thinking, incoherent speech
Perceptual disturbances: illusions, hallucinations (often visual)
Altered sleep-wake cycle
Subtypes: hyperactive (agitation, hypervigilance), hypoactive (lethargy, withdrawal — most common in elderly and most often missed), mixed
Mood lability, emotional outbursts, paranoia
Memory deficits

Signs / physical exam

Reduced ability to attend (e.g., months backward, serial 7s, digit span)
Disorientation to time/place
Tremor, asterixis, myoclonus in metabolic encephalopathies
Pinpoint pupils (opioid), mydriasis and tachycardia (anticholinergic or stimulant)
Focal neurologic signs suggest structural cause and warrant imaging
Vital sign abnormalities reflecting underlying illness

Classic findings

Inattention with acute, fluctuating onset is the hallmark; the Confusion Assessment Method (CAM) operationalizes this.

Differential diagnosis

Dementia — Chronic, slow onset, attention relatively preserved early, level of arousal normal; delirium can be superimposed on dementia (and often is)
Depression (pseudodementia) — Persistent low mood, anhedonia, sleep/appetite changes; cognition impaired but attention often intact; subacute
Primary psychiatric illness (psychosis, mania, dissociative) — Usually younger, preserved level of consciousness, sustained psychotic content, history of mental illness
Nonconvulsive status epilepticus — Confusion without obvious convulsion; EEG diagnostic — must consider in any unexplained altered mental status
Wernicke encephalopathy — Triad of confusion, ophthalmoplegia, ataxia; alcohol use, malnutrition, bariatric surgery, hyperemesis; give thiamine BEFORE glucose
Stroke (especially right MCA, thalamic, occipital) — Focal deficits, abrupt onset; imaging
CNS infection (meningitis, encephalitis, brain abscess) — Fever, headache, meningismus, focal signs; LP and imaging
Hepatic encephalopathy — Cirrhosis, asterixis, elevated ammonia, hepatic stigmata
Hypoglycemia or hyperglycemic crises — Fingerstick glucose; rapid reversal with treatment

Diagnostic workup

Diagnostic criteria

DSM-5: (A) disturbance of attention and awareness; (B) develops over short period, fluctuates; (C) additional cognitive disturbance; (D) not better explained by another neurocognitive disorder or coma; (E) evidence of underlying physiologic cause. CAM: (1) acute onset and fluctuating course + (2) inattention + either (3) disorganized thinking or (4) altered level of consciousness.

Labs

CBC with diff, BMP (Na, glucose, BUN/Cr, Ca), magnesium, phosphorus, LFTs, ammonia (if hepatic), TSH
Urinalysis and culture, blood cultures if febrile
ABG/VBG if hypoxia or hypercapnia suspected
Drug levels (lithium, digoxin, anticonvulsants); urine toxicology
Troponin and ECG if cardiac etiology suspected
Lumbar puncture if CNS infection or unexplained encephalopathy
Vitamin B12, thiamine (give empirically if Wernicke suspected)

Imaging

CT head if focal deficits, head trauma, anticoagulation, or no identifiable cause
MRI brain if CT non-diagnostic and concern for stroke or PRES
Chest X-ray for occult pneumonia
EEG if nonconvulsive seizures suspected (also shows generalized slowing in metabolic delirium)

Diagnostic algorithm

Feature	Delirium	Dementia	Depression
Onset	Hours to days	Months to years	Weeks to months
Course	Fluctuating, worse at night	Slowly progressive	Persistent low mood
Attention	Markedly impaired	Preserved early	May be mildly impaired
Level of consciousness	Altered (hyper- or hypoactive)	Normal until late	Normal
Orientation	Impaired	Impaired late	Usually intact
Hallucinations	Common (visual)	Late-stage (or DLB)	Rare (psychotic depression)
Reversibility	Usually reversible	Generally not reversible	Reversible with treatment

Distinguishing delirium, dementia, and depression in older adults.

Treatment

First-line

Identify and treat the underlying cause(s) — usually multifactorial (the 'I WATCH DEATH' or similar mnemonic): Infection, Withdrawal, Acute metabolic, Trauma, CNS pathology, Hypoxia, Deficiencies, Endocrine, Acute vascular, Toxins/drugs, Heavy metals
Nonpharmacologic 'HELP'-style bundle (Hospital Elder Life Program): orient frequently (clock, calendar, familiar faces), restore sensory aids (glasses, hearing aids), early mobilization, sleep hygiene (quiet, dark at night; light during day; minimize nighttime interruptions), hydration and nutrition, avoid restraints and tethers
Review and minimize deliriogenic medications: anticholinergics (diphenhydramine, oxybutynin, TCAs), benzodiazepines, opioids (especially meperidine), corticosteroids, H2 blockers; deprescribe when possible
Treat pain (scheduled acetaminophen; avoid meperidine), constipation, urinary retention; reassess Foley catheters daily
ABCDEF bundle in ICU: Assess/manage pain, spontaneous Breathing trials, Choice of sedation (avoid benzodiazepines; prefer dexmedetomidine or propofol), Delirium monitoring (CAM-ICU), Early mobility, Family engagement

Second-line / adjunct

Pharmacologic treatment ONLY for severe agitation threatening safety after nonpharmacologic measures fail:
Low-dose haloperidol (e.g., 0.25-0.5 mg PO/IM; QT monitoring); avoid in Parkinson disease and Lewy body dementia
Atypicals: quetiapine, olanzapine, risperidone — useful when EPS or PD considerations apply
Dexmedetomidine (alpha-2 agonist) for ICU delirium — reduces incidence and duration
Benzodiazepines ONLY for alcohol/sedative-hypnotic withdrawal delirium or seizures; otherwise worsen delirium
Treat alcohol withdrawal with symptom-triggered benzodiazepines (CIWA) plus thiamine, folate, multivitamins
AVOID physical restraints when possible — increase agitation and injury

Complications

Prolonged hospitalization and higher mortality (in-hospital and at 1 year)
Functional decline and loss of independence
Persistent cognitive impairment and increased risk of subsequent dementia (especially after ICU delirium)
Falls, fractures, pressure ulcers, aspiration pneumonia
Self-injury or injury to staff during severe agitation
Caregiver and family distress
PTSD-like symptoms after ICU stay

PANCE pearls

Delirium is a medical emergency — find the cause. The default assumption in older adults with acute confusion is delirium until proven otherwise.
Hypoactive delirium is MORE common than hyperactive in elderly and is frequently missed — screen all hospitalized older patients (e.g., CAM, 4AT).
If giving glucose to a patient who may be alcohol-dependent or malnourished, give thiamine FIRST to avoid precipitating Wernicke encephalopathy.
Benzodiazepines worsen non-withdrawal delirium — reserve them for alcohol/sedative withdrawal.
Avoid antipsychotics in Parkinson disease and Lewy body dementia (severe neuroleptic sensitivity); use quetiapine or pimavanserin if absolutely needed.
Postoperative delirium peaks on hospital day 2-3; preventive bundles (HELP) reduce incidence by ~30-40%.

References

DSM-5-TR — American Psychiatric Association Diagnostic and Statistical Manual, 5th ed. Text Revision (2022)
SCCM 2018 — Clinical Practice Guidelines for the Prevention and Management of PAD/Delirium/Immobility/Sleep Disruption in Adult ICU Patients (Devlin et al., Crit Care Med 2018)
AGS 2014 — American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults (Inouye et al., JAGS 2015)
CAM — Confusion Assessment Method (Inouye et al., Ann Intern Med 1990)

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