Delirium

Delirium is an acute, transient, fluctuating disturbance of attention and awareness arising from an underlying medical cause. It is a medical emergency masquerading as a psychiatric problem, and the single most common neuropsychiatric syndrome in hospitalised and post-operative patients. For NEET PG, it is a perennial favourite for its sharp contrast with dementia and its classic drug precipitants.

Definition and core concept

Delirium (synonyms: acute confusional state, acute organic brain syndrome, toxic-metabolic encephalopathy, ICU psychosis) is defined by the DSM-5 around five anchoring features:

1. Disturbance of attention (reduced ability to direct, focus, sustain, shift attention) and awareness (reduced orientation to environment).
2. Acute onset (hours to days) with a fluctuating course over the day — characteristically worse at night ("sundowning").
3. An additional cognitive disturbance (memory deficit, disorientation, language, perception).
4. Not better explained by a pre-existing/established dementia and not in the context of a severely reduced level of arousal such as coma.
5. Evidence of an underlying medical/physiological cause (the "organic" basis) from history, examination, or labs.

High-yield: The hallmark of delirium is INATTENTION with a fluctuating level of consciousness. If consciousness is clear and stable, think dementia, not delirium.

The cardinal disturbance is in the level of consciousness/arousal — this is what separates it from most primary psychiatric disorders, where the sensorium is clear.

Classification (clinical subtypes)

Delirium is classified by psychomotor activity, which has prognostic and therapeutic relevance.

Subtype	Features	Common settings	Prognosis
Hyperactive	Agitation, restlessness, hyper-vigilance, hallucinations, combativeness	Alcohol/benzodiazepine withdrawal, drug intoxication	Best recognised; better outcome
Hypoactive	Lethargy, somnolence, withdrawal, slowed responses, apathy	Elderly, metabolic/hepatic encephalopathy, sepsis	Often missed; worst prognosis, highest mortality
Mixed	Alternates between hyper- and hypoactive within hours	Most common in practice	Intermediate

High-yield: The hypoactive subtype is the most commonly missed (mistaken for depression or fatigue) and carries the worst prognosis and highest mortality. The mixed type is the commonest overall.

Epidemiology and risk factors

Delirium results from the interaction of predisposing vulnerability + a precipitating insult. A frail patient needs only a trivial trigger; a robust patient needs a major one.

Predisposing (baseline vulnerability)	Precipitating (acute triggers)
Age > 65, pre-existing dementia	Drugs (esp. anticholinergics, sedatives, opioids)
Sensory impairment (vision/hearing)	Infection (UTI, pneumonia, sepsis)
Multiple comorbidities, frailty	Surgery / anaesthesia, ICU admission
Prior delirium, alcohol dependence	Metabolic derangement, dehydration
Polypharmacy, malnutrition	Urinary retention, faecal impaction, pain

• Dementia is the strongest predisposing factor — up to two-thirds of delirium occurs superimposed on dementia.
• Incidence is highest in post-operative (esp. hip fracture, cardiac surgery) and ICU patients (up to 70–80% of ventilated patients).

High-yield: Always ask — "What is the precipitant?" In the elderly, the commonest reversible causes are drugs, infection (UTI), and electrolyte/metabolic disturbance. Urinary retention and constipation are classic occult triggers.

Etiology — mnemonics worth memorising

A practical screening list is "I WATCH DEATH":

• I — Infection (pneumonia, UTI, sepsis, encephalitis)
• W — Withdrawal (alcohol, benzodiazepines, barbiturates)
• A — Acute metabolic (acidosis, electrolytes, hepatic/renal failure)
• T — Trauma (head injury, post-op, burns)
• C — CNS pathology (stroke, haemorrhage, tumour, seizures, abscess)
• H — Hypoxia (anaemia, hypotension, cardiac/respiratory failure)
• D — Deficiencies (thiamine → Wernicke, B12, niacin, folate)
• E — Endocrinopathies (thyroid, glucose, adrenal, parathyroid)
• A — Acute vascular (hypertensive encephalopathy, shock)
• T — Toxins/drugs (anticholinergics, opioids, sedatives, lithium, digoxin)
• H — Heavy metals (lead, mercury, manganese)

A simpler bedside aid is "DELIRIUM(S)": Drugs, Electrolytes, Lack of drugs (withdrawal), Infection, Reduced sensory input, Intracranial, Urinary/faecal retention, Myocardial/pulmonary, (S)leep deprivation.

Drug-induced delirium (very high-yield)

Drugs are responsible for up to 30–40% of cases. The most notorious class is anticholinergics.

• Anticholinergic delirium: confusion + classic toxidrome — "mad as a hatter, red as a beet, hot as a hare, dry as a bone, blind as a bat, the heart runs alone" (delirium, flushing, hyperthermia, dry skin/mucosae, mydriasis, tachycardia, urinary retention). Offenders: atropine, scopolamine, tricyclic antidepressants, oxybutynin, antihistamines (diphenhydramine, promethazine), antiparkinsonian agents (trihexyphenidyl, benztropine), low-potency antipsychotics, antispasmodics.
• Antidote for severe central anticholinergic toxicity = physostigmine (a tertiary-amine cholinesterase inhibitor that crosses the blood–brain barrier).
• Other culprits: opioids (esp. pethidine/meperidine via its metabolite normeperidine), benzodiazepines, corticosteroids ("steroid psychosis"), lithium, digoxin, theophylline, levodopa, fluoroquinolones, H2-blockers (cimetidine).

High-yield: A confused elderly patient on oxybutynin, TCAs, or diphenhydramine = think anticholinergic delirium. Severe central anticholinergic syndrome is reversed by physostigmine.

Pathophysiology

The final common pathway is diffuse cerebral dysfunction. Several interlinked mechanisms are tested:

1. Neurotransmitter imbalance — the central theme is acetylcholine deficiency combined with dopamine excess. This explains why anticholinergic drugs precipitate delirium and why dopamine-blocking antipsychotics (haloperidol) treat it.
2. Neuroinflammation — systemic inflammation (sepsis, surgery) → pro-inflammatory cytokines (IL-1, IL-6, TNF-α) → microglial activation and blood–brain barrier disruption.
3. Oxidative stress / impaired oxidative metabolism — hypoxia and metabolic failure reduce cerebral oxidative metabolism.
4. Other transmitters — relative excess of glutamate and noradrenaline; abnormal GABA, serotonin and melatonin signalling (the latter explaining circadian/sleep disruption and sundowning).

Stepwise model: Predisposing vulnerability (low cholinergic reserve) → acute precipitant (drug/infection/metabolic) → neurotransmitter imbalance + neuroinflammation → diffuse cortical and subcortical dysfunction → clinical delirium.

High-yield: Core neurochemistry of delirium = ↓ acetylcholine + ↑ dopamine. This single fact unifies the etiology (anticholinergics trigger it) and treatment (dopamine blockers reverse it).

The EEG correlate is diffuse, generalised slowing of background rhythm (theta/delta) — a useful exam point. The exception is delirium tremens / sedative withdrawal, where the EEG shows fast, low-voltage activity.

Clinical features

• Disturbed attention/consciousness — patient is easily distracted, cannot maintain conversation, drifts off; clouding of the sensorium that waxes and wanes.
• Disorientation — time first, then place, then person.
• Cognitive impairment — poor short-term memory, registration deficits.
• Perceptual disturbances — illusions and visual hallucinations (often vivid, frightening; e.g., insects/animals — Lilliputian hallucinations in DT).
• Thought disorganisation — incoherent, rambling speech; transient, poorly systematised persecutory delusions.
• Sleep–wake cycle disruption — reversal of cycle, daytime drowsiness, nocturnal agitation (sundowning).
• Emotional lability — fear, irritability, perplexity, anxiety.
• Psychomotor changes — agitation (hyper) or stupor (hypo); asterixis, myoclonus, tremor point to metabolic causes (hepatic/uraemic).
• Autonomic features — tachycardia, sweating, hypertension (prominent in withdrawal states).

High-yield: Visual hallucinations favour an organic/delirious cause; purely auditory hallucinations favour a primary psychiatric disorder (schizophrenia).

Diagnosis and investigations

Delirium is a clinical, bedside diagnosis. The key is recognition + finding the cause.

Screening and diagnostic instruments

• CAM (Confusion Assessment Method) — the most widely used bedside tool. Diagnosis requires features 1 AND 2, plus either 3 OR 4:

  1. Acute onset and fluctuating course (required)
  2. Inattention (required)
  3. Disorganised thinking
  4. Altered level of consciousness

  So: (1 + 2) + (3 or 4) = delirium.

• CAM-ICU — validated version for ventilated/non-verbal ICU patients.

• 4AT — rapid screen (Alertness, AMT-4, Attention via months backwards, Acute change).

• MMSE is not diagnostic for delirium but documents global cognitive impairment.

High-yield: The CAM algorithm — (acute/fluctuating + inattention) + (disorganised thinking OR altered consciousness) — is the single most asked diagnostic criterion set for delirium.

Investigation of choice / workup

There is no single test for delirium; investigations are aimed at the underlying cause.

Stepwise workup: Bedside (vitals, capillary glucose, SpO₂, GCS) → basic labs (CBC, electrolytes including Na/Ca, urea/creatinine, LFT, TSH, urinalysis/culture, blood culture) → ABG, B12/folate/thiamine if indicated → ECG, chest X-ray → targeted neuroimaging (CT/MRI brain) if focal signs, head trauma, or no cause found → EEG (shows diffuse slowing; useful to confirm organicity or detect non-convulsive status) → lumbar puncture if meningoencephalitis suspected.

• EEG: confirms the organic nature (generalised slowing) and is the classic answer when asked for the electrophysiological investigation, but it is rarely needed routinely.
• In suspected Wernicke encephalopathy (confusion + ophthalmoplegia + ataxia in an alcoholic), give thiamine BEFORE glucose to avoid precipitating/worsening the encephalopathy.

Differential diagnosis — Delirium vs Dementia (the examiner's favourite)

Feature	Delirium	Dementia
Onset	Acute (hours–days)	Insidious (months–years)
Course	Fluctuating, worse at night	Slowly progressive, stable over a day
Consciousness/arousal	Impaired / clouded	Clear (until terminal stages)
Attention	Markedly impaired (hallmark)	Relatively preserved early
Hallucinations	Common, visual	Less common (except DLB)
Sleep–wake cycle	Disrupted, reversed	Usually normal early
Psychomotor activity	Increased or decreased	Usually normal
Reversibility	Often reversible	Generally irreversible
EEG	Diffuse slowing (usually)	Normal or mild slowing

High-yield: The two discriminators most asked — delirium = acute + fluctuating + impaired consciousness + inattention; dementia = chronic + stable + clear consciousness. When both coexist ("delirium superimposed on dementia"), the acute change in attention/consciousness signals delirium.

Other differentials

• Depression (pseudodementia) — can mimic hypoactive delirium; mood-congruent, no clouding, consciousness clear, attention better with effort.
• Primary psychosis (schizophrenia, mania) — clear sensorium, systematised delusions, auditory hallucinations, no fluctuating consciousness, normal EEG.
• Non-convulsive status epilepticus — fluctuating confusion; EEG diagnostic.
• Wernicke encephalopathy, transient global amnesia, dissociative states.

Delirium	Psychosis (functional)
Clouded, fluctuating consciousness	Clear consciousness
Visual hallucinations predominate	Auditory hallucinations predominate
Disorientation common	Usually oriented
EEG abnormal (slowing)	EEG normal
Identifiable medical cause	No organic cause

Management

General principles (treat the cause + supportive care first)

1. Identify and treat the underlying cause — this is the definitive treatment (stop offending drug, treat infection, correct electrolytes/hypoxia/hypoglycaemia).
2. Non-pharmacological measures are first-line for behaviour ("reorientation bundle"): well-lit, quiet room; clock and calendar visible; presence of family; restore glasses and hearing aids; maintain hydration and nutrition; promote a normal sleep–wake cycle; mobilise early; avoid restraints and minimise lines/catheters; address pain and constipation.
3. Medication review — withdraw anticholinergics, sedatives, opioids where possible.

High-yield: The most effective intervention in delirium is treating the underlying precipitant plus non-pharmacological supportive care. Drugs are reserved for severe agitation that threatens safety.

Pharmacotherapy — drug of choice

• Haloperidol is the drug of choice / first-line for agitation in delirium — a high-potency typical antipsychotic with minimal anticholinergic and hypotensive effects. Low dose (0.5–1 mg), titrated; can be given oral/IM/IV.
  • Monitor QTc prolongation (risk of torsades) and extrapyramidal symptoms.
• Atypical antipsychotics (risperidone, olanzapine, quetiapine) — increasingly preferred in the elderly and in Parkinson's/Lewy body disease (use quetiapine here, as it has least EPS).

High-yield: DOC for delirium-related agitation = Haloperidol. Watch the QTc.

Important exceptions where benzodiazepines are first-line

• Alcohol withdrawal / delirium tremens and sedative–hypnotic (benzodiazepine/barbiturate) withdrawal → benzodiazepines are first-line (e.g., lorazepam, chlordiazepoxide, diazepam). Lorazepam is favoured in hepatic dysfunction. Add thiamine.
• Hepatic encephalopathy → avoid/limit benzodiazepines and antipsychotics; treat with lactulose/rifaximin; use the lowest effective sedation.
• Antipsychotic-sensitive states (Parkinson's disease, dementia with Lewy bodies — risk of severe neuroleptic sensitivity) → avoid haloperidol; prefer quetiapine.

High-yield: Benzodiazepines worsen most deliriums and should be avoided except in alcohol/sedative withdrawal (where they are the DOC). Routine use of benzodiazepines is a leading iatrogenic cause of delirium.

Complications and prognosis

• Increased mortality (in-hospital and at 6–12 months), prolonged hospital stay, higher rates of institutionalisation.
• Persistent cognitive decline — delirium accelerates and may unmask dementia; an episode of delirium is an independent risk factor for new long-term cognitive impairment.
• Falls, pressure ulcers, aspiration, functional decline, and complications of restraints.
• Distress to patient and carers; post-delirium PTSD-like symptoms in ICU survivors.

High-yield: Delirium is not always benign or fully reversible — it independently predicts higher mortality and future dementia, especially the hypoactive subtype.

Recently asked / exam angle

NEET PG and INI-CET have repeatedly tested the following angles:

• Delirium vs dementia comparison table — single-best-answer on onset, consciousness, attention, reversibility.
• CAM criteria — identifying the required components: acute/fluctuating + inattention plus disorganised thinking or altered consciousness.
• Drug of choice = haloperidol; and the exception that benzodiazepines are first-line in alcohol withdrawal/DT.
• Anticholinergic delirium — recognising the toxidrome and that physostigmine is the antidote; identifying offending drugs (oxybutynin, TCAs, diphenhydramine, atropine).
• Hypoactive delirium is the most missed and has the worst prognosis.
• EEG finding = diffuse generalised slowing (fast activity in DT/sedative withdrawal).
• Neurochemistry: decreased ACh, increased dopamine.
• Wernicke: give thiamine before glucose in an alcoholic with acute confusion.
• Clinical vignette: post-operative/elderly patient on multiple drugs with fluctuating confusion worse at night → answer delirium; first step → identify and treat the cause / review medications.
• Visual hallucinations suggest organic delirium vs auditory in functional psychosis.

Rapid revision

1. Delirium = acute, fluctuating disturbance of attention + awareness with an organic cause.
2. Inattention is the cardinal feature; consciousness is clouded/fluctuating (clear in dementia).
3. Subtypes: hyperactive, hypoactive (most missed, worst prognosis), mixed (commonest).
4. Strongest predisposing factor = pre-existing dementia; commonest precipitants = drugs, infection (UTI), metabolic.
5. Etiology mnemonic = I WATCH DEATH.
6. Core neurochemistry = ↓ acetylcholine, ↑ dopamine.
7. Anticholinergic toxidrome (TCAs, oxybutynin, diphenhydramine) → antidote physostigmine.
8. Diagnosis by CAM: (acute/fluctuating + inattention) + (disorganised thinking OR altered consciousness).
9. EEG = diffuse slowing (fast activity in delirium tremens).
10. DOC = haloperidol (watch QTc); use quetiapine in Parkinson's/Lewy body.
11. Benzodiazepines = first-line only in alcohol/sedative withdrawal; otherwise they worsen delirium.
12. Management priority = treat the cause + non-pharmacological supportive care; delirium independently raises mortality and risk of future dementia.