Delirium

Clinical picture

• Attention fails first: the patient cannot sustain focus, loses the thread of questions, and needs repeated redirection throughout the interview.
• Symptoms fluctuate across hours and are typically worse at night, so a calm morning exam can miss an episode well documented by overnight nursing.
• Hypoactive delirium, meaning quiet withdrawal and somnolence, is the most common and most missed subtype and carries the worst overall prognosis.
• Hyperactive presentations bring agitation, pulling at lines, and combative behavior, and are frequently mislabeled as primary psychiatric decompensation.
• Perceptual disturbance includes visual hallucinations, illusions, and fleeting paranoid delusions, accompanied by disorientation to time and place.
• Sleep-wake cycle reversal, emotional lability, and disorganized rambling speech round out the picture alongside altered psychomotor activity.

Criteria snapshot

• A disturbance in attention and awareness develops acutely, over hours to a few days, and represents a clear change from the person's baseline.
• Severity fluctuates over the course of a day, a defining feature that separates it from the stable deficits of a major neurocognitive disorder.
• An additional cognitive disturbance is present in memory, orientation, language, visuospatial ability, or perception beyond the attentional problem.
• The disturbance is not better explained by an established or evolving neurocognitive disorder and does not occur in the context of severe coma.
• Evidence indicates a medical condition, substance intoxication or withdrawal, a medication, a toxin, or multiple etiologies as the direct cause.

Neurobiology

• Cholinergic deficiency with relative dopaminergic excess is the leading model, explaining why anticholinergic drugs precipitate episodes so reliably.
• Systemic inflammation drives neuroinflammation as IL-1, IL-6, and TNF-alpha cross a compromised blood-brain barrier and activate resident microglia.
• Impaired oxidative metabolism from hypoxia, hypoglycemia, sepsis, or hypoperfusion reduces neurotransmitter synthesis and degrades network connectivity.
• EEG shows diffuse background slowing with increased theta and delta activity, a useful confirmatory test when the clinical diagnosis is uncertain.
• Baseline vulnerability from dementia, advanced age, frailty, sensory impairment, and prior stroke lowers the insult required to precipitate an episode.
• Episodes accelerate long-term cognitive decline, and both severity and duration predict persistent deficits and new dementia diagnoses at 12 months.

Psychology

• Delirium is a physiologic event rather than a psychological one, so psychological factors modify its expression and distress but do not cause the syndrome.
• Sensory deprivation and sensory overload, meaning absent windows, constant alarms, and interrupted sleep, measurably raise incidence in ICU settings.
• Loss of familiar anchors such as glasses, hearing aids, family, and routine removes the orienting cues that compensate for already fragile attention.
• Patients recall frightening delusional memories in 30-50% of cases, and those memories predict later PTSD symptoms after discharge from intensive care.
• Family and staff distress is substantial, and explaining the medical basis and the expected fluctuation reduces conflict and improves cooperation with care.

Differential & comorbidity

• Dementia is distinguished by insidious onset, attention preserved early, and a stable rather than fluctuating course, though delirium is superimposed in most cases.
• Nonconvulsive status epilepticus, Wernicke encephalopathy, and acute stroke can mimic delirium and require EEG, empiric thiamine, and urgent imaging.
• Depression is misdiagnosed in hypoactive cases and mania or psychosis in hyperactive cases, and formal attention testing separates them within minutes.
• Common causes cluster as infection, metabolic derangement, hypoxia, medications, withdrawal, urinary retention, constipation, and uncontrolled pain.
• Alcohol and sedative withdrawal delirium is life-threatening and demands protocolized benzodiazepine treatment, thiamine, and close monitoring.

Pharmacologic treatment

• Treat the underlying cause first, since no medication is FDA-approved for delirium and antipsychotics do not shorten duration or reduce mortality.
• For dangerous agitation use low-dose haloperidol 0.25-1 mg or quetiapine 12.5-50 mg at night, reassessed daily and stopped once the episode resolves.
• Avoid benzodiazepines except in alcohol or sedative withdrawal, where symptom-triggered lorazepam by CIWA protocol is the established first-line treatment.
• Give thiamine 500 mg IV three times daily before glucose whenever Wernicke encephalopathy or chronic heavy alcohol use is suspected.
• Deprescribe offending agents including anticholinergics, unnecessary opioids, sedative-hypnotics, and steroids, guided by the Beers criteria.

Psychotherapy

• Formal psychotherapy has no role during the acute episode because attention is too impaired to support any cognitive or verbal intervention.
• Frequent reorientation to name, place, date, and reason for admission, delivered calmly and repeatedly, is the core behavioral intervention at the bedside.
• Family presence at the bedside with familiar objects and voices reduces agitation and lowers the need for chemical or physical restraint.
• After recovery, debrief the patient about delusional memories to reduce residual distress and screen for PTSD symptoms at outpatient follow-up.
• Educate caregivers that the recovery arc is measured in weeks to months rather than days, which prevents premature nursing home placement decisions.

Adjunct options

• Multicomponent prevention such as the HELP program cuts incidence roughly 30-40% through mobility, hydration, sleep, and orientation protocols.
• Screen daily with the CAM, CAM-ICU, or the 4AT in acute care, because routine clinical observation misses more than half of all episodes.
• Restore glasses and hearing aids, mobilize early, and remove tethers such as urinary catheters, telemetry lines, and restraints as soon as possible.
• Protect sleep with nonpharmacologic bundles including clustered care, daytime light exposure, nighttime quiet, and no routine overnight vital signs.
• Avoid physical restraints, which prolong delirium and increase injury, and use sitters, redirection, and de-escalation techniques instead.

Clinical pearls

• Inattention is the cardinal sign; if attention is intact, question the diagnosis.
• Hypoactive delirium is the common one, the missed one, and the deadly one.
• Antipsychotics manage agitation; only fixing the cause treats the delirium.