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 |
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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