Delirium (Acute Confusional State)

1. Clinical Overview

Delirium is an acute, fluctuating disturbance of consciousness, attention, and cognition that represents "acute brain failure" in response to a physiological stressor. It is a medical emergency and a powerful independent predictor of adverse outcomes in hospitalised patients. [1,2]

Delirium affects approximately 20% of general hospital admissions, rising to 50% in hip fracture patients and 80% in intensive care units. [3,4] Despite its frequency, delirium remains under-recognised, particularly the hypoactive subtype, leading to delayed diagnosis and preventable harm. [5]

The condition is not simply a marker of underlying illness but an independent risk factor for mortality, increased length of stay, institutionalisation, and accelerated cognitive decline. [6,7] Mortality is doubled in delirious hospitalised patients compared to non-delirious controls, even after adjusting for comorbidities and illness severity. [8]

Key Clinical Principles

Delirium is a Clinical Diagnosis: No laboratory test or imaging can confirm or exclude delirium. The diagnosis relies on bedside assessment, serial observations, and collateral history from those who know the patient's baseline. [9]

Think "Vulnerable Brain": Delirium results from the interplay between predisposing factors (patient vulnerability) and precipitating factors (acute insults). A robust 20-year-old requires a massive insult (e.g., severe sepsis, head trauma) to become delirious. A frail 90-year-old with dementia, polypharmacy, and sensory impairment may develop delirium from a seemingly minor trigger such as constipation or a single dose of codeine. [10]

Prevention is Better Than Cure: Up to 40% of delirium cases are preventable through multicomponent interventions targeting modifiable risk factors. [11] Once established, delirium is difficult to treat, making prevention a priority in high-risk populations.

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2. Clinical Phenotypes

Delirium presents in three motor subtypes, each with different clinical features, recognition rates, and outcomes. [12]

Hyperactive Delirium (25-30%)

Presentation: Agitation, restlessness, aggressive behaviour, wandering, hallucinations, and psychomotor hyperactivity. Patients are often combative, pull out lines and catheters, and attempt to leave the ward.

Recognition: Easy to spot. Often prompts emergency psychiatric consultation or sedation.

Pitfall: Frequently mismanaged with excessive sedation rather than identification and treatment of the underlying cause. This can deepen delirium and worsen outcomes. [13]

Hypoactive Delirium (25-30%)

Presentation: Reduced motor activity, lethargy, drowsiness, withdrawal, reduced speech, and apathy. Patients appear "sleepy" or "quiet" and are easily overlooked on busy wards.

Recognition: Frequently missed. Often dismissed as "tired," "depressed," or "sleeping well." The patient is not making demands, so receives less nursing attention. [14]

Pitfall: Associated with worse outcomes than hyperactive delirium due to delayed diagnosis, increased risk of aspiration pneumonia, pressure ulcers, and venous thromboembolism. [15]

Clinical Pearl: "The quiet patient may be the sickest." Always screen patients who are "unusually quiet" or "sleeping more than usual."

Mixed Delirium (40-50%)

Presentation: Fluctuation between hyperactive and hypoactive states, often within hours. A patient may be agitated at night and somnolent during the day.

Recognition: Can be identified if serial assessments are performed. A single snapshot assessment may miss the fluctuating nature. [16]

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3. Epidemiology

Prevalence and Incidence

Mortality Impact

• In-hospital mortality: Delirious patients have 2-fold increased risk compared to non-delirious controls. [8]
• 30-day mortality: 10-26% (varies by setting and severity). [22]
• 6-month mortality: 25-33% in older adults with delirium during hospitalisation. [23]
• Mortality is independent: Delirium is an independent predictor of death even after controlling for age, comorbidities, and severity of illness. [6]

Risk Factors

Delirium risk is best understood using the predisposing-precipitating model. [10]

Predisposing Factors (Patient Vulnerability)

Non-modifiable:

• Age ≥65 years (risk increases exponentially with age)
• Male sex
• Pre-existing cognitive impairment or dementia (strongest risk factor, RR 5.2) [24]
• History of previous delirium
• Stroke or neurological disease
• Depression

Modifiable:

• Polypharmacy (≥5 medications)
• Sensory impairment (visual or hearing impairment)
• Malnutrition or dehydration
• Immobility or physical frailty
• Alcohol excess or dependency
• Social isolation

Precipitating Factors (Acute Insults)

• Infection: Most common trigger (30-40% of cases). UTI, pneumonia, skin/soft tissue infection, and occult sepsis. [25]
• Medications: Especially anticholinergics, opiates, benzodiazepines, antihistamines, dopaminergic agents.
• Metabolic disturbance: Hypoglycaemia, hypo/hypernatraemia, hypercalcaemia, renal failure, hepatic encephalopathy.
• Intracranial pathology: Stroke, subdural haematoma, intracranial haemorrhage.
• Hypoxia: Respiratory failure, pulmonary embolism, cardiac failure.
• Pain: Uncontrolled pain (including fractures, urinary retention, constipation).
• Surgery: Especially orthopaedic, cardiac, and vascular procedures.
• Environmental: Sleep deprivation, unfamiliar environment, sensory overload/deprivation, physical restraint.

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4. Pathophysiology

The pathophysiology of delirium is multifactorial and incompletely understood. Leading hypotheses include neurotransmitter imbalance, neuroinflammation, oxidative stress, and blood-brain barrier disruption. [26]

Neurotransmitter Hypothesis

Cholinergic Deficiency:

• Acetylcholine is essential for attention and arousal.
• Delirium is associated with reduced cholinergic activity in the brain.
• Anticholinergic medications (e.g., oxybutynin, amitriptyline, promethazine) precipitate or worsen delirium by blocking muscarinic receptors. [27]
• Serum anticholinergic activity correlates with delirium severity in older adults. [28]

Dopaminergic Excess:

• Increased dopaminergic activity in the mesolimbic system may contribute to hallucinations, agitation, and psychomotor disturbance.
• Dopamine antagonists (e.g., haloperidol) can reduce hyperactive symptoms but do not treat the underlying cause or improve outcomes. [29]

Other Neurotransmitters:

• GABA: Benzodiazepines enhance GABAergic activity and can paradoxically worsen delirium.
• Serotonin: Serotonin syndrome or excess serotonergic activity may contribute.
• Glutamate: NMDA receptor dysfunction may play a role.

Neuroinflammation Hypothesis

Peripheral inflammatory insults (e.g., infection, surgery, trauma) trigger systemic cytokine release (IL-1, IL-6, TNF-α). These cytokines can cross the blood-brain barrier (especially in the elderly with increased permeability) and activate microglia, leading to central neuroinflammation and neuronal dysfunction. [30,31]

Elevated serum IL-6 and C-reactive protein levels are associated with delirium incidence and severity. [32]

Oxidative Stress and Metabolic Dysfunction

Acute illness leads to increased free radical production and impaired mitochondrial function. The ageing brain is particularly vulnerable due to reduced antioxidant capacity. This results in neuronal injury, impaired neurotransmitter synthesis, and energy failure. [33]

Neuroendocrine Dysfunction

Cortisol dysregulation and abnormal hypothalamic-pituitary-adrenal (HPA) axis responses are observed in delirious patients. Elevated cortisol may contribute to hippocampal dysfunction and memory impairment. [34]

The Final Common Pathway

Regardless of the precipitating cause, the final result is widespread cortical and subcortical dysfunction affecting:

• Attention and arousal: Reticular activating system and thalamus.
• Cognition and memory: Hippocampus and prefrontal cortex.
• Perception and thought: Temporo-parietal cortex.

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5. Clinical Presentation

DSM-5 Diagnostic Criteria for Delirium

A. Disturbance in attention (reduced ability to direct, focus, sustain, or shift attention) and awareness (reduced orientation to the environment).

B. The disturbance develops over a short period (usually hours to days), represents a change from baseline, and tends to fluctuate during the day.

C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception).

D. Criteria A and C are not better explained by a pre-existing or evolving neurocognitive disorder (e.g., dementia).

E. Evidence from history, examination, or investigations that the disturbance is a direct physiological consequence of a medical condition, substance intoxication/withdrawal, toxin exposure, or multiple aetiologies.

Cardinal Features

1. Acute Onset and Fluctuating Course

• Onset: Hours to days (not weeks or months).
• Fluctuation: Symptoms wax and wane, often worse at night ("sundowning"). Lucid intervals are common, leading to false reassurance. [35]
• Collateral history is essential: Ask, "Was the patient normal yesterday?" or "Is this new confusion?"

2. Inattention (Hallmark Feature)

• Reduced ability to focus: Patient is easily distracted, cannot follow a conversation or complete tasks.
• Reduced ability to sustain attention: Cannot maintain focus on a question or activity.
• Cannot shift attention: Gets "stuck" on a topic or perseverates.

Bedside tests:

• Months of the year backwards: Normal patients can complete this in < 20 seconds. Delirious patients lose track, repeat months, or give up.
• Days of the week backwards
• Serial 7s (subtract 7 from 100 repeatedly)
• Digit span (repeat digits forwards and backwards)

3. Disorientation

• Time: Date, day of week, month, year.
• Place: Name of hospital, floor, ward.
• Person: Usually preserved until late stages (unlike dementia).

4. Altered Consciousness

• Hyperalert: Heightened vigilance, easily startled.
• Drowsy: Reduced responsiveness, requires stimulation to respond.
• Stuporous or comatose: In severe cases.

5. Cognitive Disturbances

• Memory impairment: Reduced short-term and working memory. Cannot recall events from earlier in the day.
• Disorganised thinking: Rambling, irrelevant, or illogical conversation. Reduced coherence.
• Language disturbance: Dysnomia, perseveration, reduced comprehension.
• Perceptual disturbances: Hallucinations (visual > auditory) and illusions.

6. Psychomotor Disturbance

• Hyperactive: Restlessness, agitation, pacing, pulling at tubes.
• Hypoactive: Reduced activity, psychomotor slowing, lethargy.

7. Sleep-Wake Cycle Disturbance

• Fragmented sleep: Frequent waking during the night.
• Sleep-wake reversal: Asleep during the day, awake and agitated at night.
• Altered circadian rhythm: Loss of normal day-night cycle.

8. Emotional Lability

• Anxiety, fear, irritability, anger, apathy, or euphoria. Rapid shifts in mood.

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6. Delirium vs Dementia vs Depression

A common clinical dilemma in the confused older adult.

Important: Delirium and dementia frequently coexist. Dementia is the strongest risk factor for delirium. [24] A patient with baseline dementia can develop superimposed delirium (known as "delirium superimposed on dementia"). Always compare current mental state to baseline.

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7. Clinical Examination and Screening

Collateral History

The most important diagnostic tool. Always speak to family, carers, nursing staff, or GP to establish:

• Baseline cognitive function: "Was there any memory loss or confusion before this admission?"
• Onset and course: "When did the confusion start?" "Is it getting worse?" "Is it better at certain times of day?"
• Functional status: "Could they dress, cook, and manage medications independently before this illness?"

Bedside Screening Tools

Formal screening tools improve recognition, particularly of hypoactive delirium. [36]

4AT (4-item Assessment Test for Delirium)

Rapid bedside tool (< 2 minutes). Validated in hospital and ED settings. [37]

Scoring:

• 0: Delirium or severe cognitive impairment unlikely.
• 1-3: Possible cognitive impairment. Further assessment needed.
• ≥4: Probable delirium ± cognitive impairment.

CAM (Confusion Assessment Method)

Widely used tool requiring trained assessor. Four features assessed: [38]

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

Diagnosis: Features 1 AND 2 must be present, PLUS either 3 OR 4.

Sensitivity: 94%, Specificity: 89% (when performed by trained staff).

CAM-ICU (for ventilated/critically ill patients)

Adapted version for ICU patients who are intubated or non-verbal. [39]

Single Question in Delirium (SQiD)

Ultra-rapid screening by asking family or carer: "Do you think [name] has been more confused lately?" Sensitivity: 80%, Specificity: 71%. Useful as a triage tool. [40]

Physical Examination

Purpose: Identify precipitating causes and assess severity.

General Inspection

• Level of consciousness: Alert, drowsy, stuporous?
• Behaviour: Agitated, withdrawn, distracted?
• Hydration status: Dry mucous membranes, reduced skin turgor?
• Nutritional state: Cachexia, muscle wasting?

Vital Signs

• Temperature: Fever (infection), hypothermia (sepsis, hypothyroidism).
• Heart rate and rhythm: Tachycardia (sepsis, hypoxia), arrhythmia (stroke risk).
• Blood pressure: Hypotension (sepsis, dehydration), hypertension (hypertensive encephalopathy).
• Respiratory rate and oxygen saturation: Hypoxia, respiratory failure.
• Blood glucose: Hypoglycaemia, hyperglycaemia.

Neurological Examination

• Focal neurology: Hemiparesis, visual field defect, cranial nerve palsy (suggests stroke, subdural, mass lesion).
• Meningism: Neck stiffness, photophobia (meningitis, encephalitis, subarachnoid haemorrhage).
• Cerebellar signs: Ataxia, nystagmus, dysmetria (Wernicke's encephalopathy, posterior circulation stroke).
• Ophthalmoplegia: Wernicke's encephalopathy (lateral rectus palsy, gaze palsy).
• Pupils: Pin-point (opiate toxicity), dilated (anticholinergic toxicity).
• Tremor: Fine tremor (alcohol withdrawal, thyrotoxicosis), flapping tremor (hepatic or uraemic encephalopathy, CO2 retention).

Systems Examination

• Cardiovascular: Murmurs (endocarditis), JVP (heart failure, fluid overload).
• Respiratory: Crackles (pneumonia, heart failure), reduced air entry (pleural effusion, consolidation).
• Abdominal: Distension (constipation, urinary retention, bowel obstruction), tenderness (peritonitis, cholecystitis).
• Skin: Rashes (cellulitis, drug reaction), pressure ulcers (infection source).
• Bladder scan: Urinary retention.

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8. Differential Diagnosis

1. Dementia

Key differences: Chronic onset, stable day-to-day, preserved attention (early stages), clear consciousness.

Caveat: Delirium can occur in patients with dementia ("delirium superimposed on dementia"). Always ask: "Is this worse than their baseline?"

2. Depression (Pseudodementia)

Older adults with severe depression may present with cognitive slowing, poor concentration, and apparent memory loss.

Key differences: Gradual onset, worse mood in morning, preserved attention, responds to antidepressants.

Screening: PHQ-9, Geriatric Depression Scale.

3. Psychosis (Late-onset schizophrenia, delusional disorder)

Key differences: Chronic course, complex delusions, auditory hallucinations, normal attention and consciousness.

4. Non-convulsive Status Epilepticus

Rare but must not miss. Presents with fluctuating confusion, reduced consciousness, and subtle motor signs (lip-smacking, eye deviation). Requires EEG for diagnosis. [41]

5. Wernicke's Encephalopathy

Acute confusional state due to thiamine (vitamin B1) deficiency. Classically presents with the triad of:

• Confusion/delirium
• Ataxia
• Ophthalmoplegia

Risk factors: Alcohol excess, malnutrition, hyperemesis, prolonged fasting, bariatric surgery.

Management: Immediate IV thiamine (Pabrinex) before glucose (glucose can precipitate or worsen Wernicke's in thiamine-deficient patients). [42]

6. Drug Intoxication or Withdrawal

• Alcohol withdrawal: Tremor, sweating, tachycardia, visual hallucinations, seizures. Onset 6-48h after last drink.
• Benzodiazepine withdrawal: Anxiety, tremor, perceptual disturbances. Onset days to weeks after cessation.
• Anticholinergic toxicity: Dry mouth, dilated pupils, urinary retention, flushed skin, hyperthermia. "Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter."

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9. Investigations

Principle: Investigate to identify and treat the underlying cause. Delirium is a clinical diagnosis—there is no "delirium test."

First-Line (Mandatory in All Cases)

Second-Line (Selected Cases)

The "PINCH ME" Mnemonic for Causes

A systematic approach to identifying precipitants:

• Pain (fractures, urinary retention, constipation, pressure ulcers)
• Infection (pneumonia, UTI, skin/soft tissue, occult sepsis)
• Nutrition (B12/folate deficiency, thiamine deficiency, hypoglycaemia)
• Neurological (stroke, subdural, seizures)
• Constipation / Catheter (urinary retention, faecal impaction)
• Hydration (dehydration, AKI) / Hypoxia (respiratory failure, heart failure, PE)
• Medications (anticholinergics, opiates, benzodiazepines, polypharmacy)
• Metabolic (Na, Ca, glucose, renal, hepatic)
• Environment (sleep deprivation, unfamiliar ward, sensory deprivation/overload, physical restraint)

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10. Management

Overarching Principles

1. Delirium is a medical emergency: Identify and treat the underlying cause urgently.
2. Non-pharmacological interventions are first-line: Multicomponent interventions reduce delirium incidence and duration. [11,43]
3. Pharmacological sedation is last resort: Use only when absolutely necessary (risk to self or others). Sedatives can worsen delirium and increase mortality. [44]
4. Involve multidisciplinary team: Nursing, pharmacy, physiotherapy, occupational therapy, family.

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Management Algorithm

CONFUSED PATIENT (Suspected Delirium)
         ↓
IMMEDIATE SAFETY ASSESSMENT (ABCDE)
- Airway, Breathing, Circulation
- Check glucose, oxygen saturation
- Stabilise life-threatening issues
         ↓
CONFIRM DIAGNOSIS (Clinical + Screening Tool)
- Collateral history (baseline function)
- 4AT or CAM
- Acute onset? Fluctuating? Inattention?
         ↓
IDENTIFY PRECIPITATING CAUSE (PINCH ME)
- Investigations (bloods, urine, CXR, etc.)
- Medication review (stop deliriogenic drugs)
- Examine for infection, pain, retention, hypoxia
         ↓
TREAT UNDERLYING CAUSE
- Antibiotics for infection
- Fluids for dehydration
- Analgesia for pain
- Laxatives for constipation
- Catheter for retention
- Oxygen for hypoxia
         ↓
NON-PHARMACOLOGICAL INTERVENTIONS (First-Line)
- Reorientation (clocks, calendars, familiar objects)
- Sensory aids (glasses, hearing aids)
- Reduce ward noise and stimulation
- Normalise sleep-wake cycle (natural light, avoid night disturbance)
- Early mobilisation and rehabilitation
- Nutrition and hydration support
- Involve family at bedside
         ↓
MONITOR RESPONSE
- Serial 4AT or CAM assessments
- Review precipitants daily
- Stop unnecessary medications
         ↓
SEVERE AGITATION / DANGER TO SELF OR OTHERS?
  ┌───────────┴───────────┐
 NO                      YES
  ↓                       ↓
CONTINUE              CONSIDER
SUPPORTIVE         PHARMACOLOGICAL
CARE                 SEDATION
                    (Lowest dose, shortest duration)

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Non-Pharmacological Management (First-Line)

The Hospital Elder Life Program (HELP) demonstrated that multicomponent interventions reduce delirium incidence by 40% and duration by 50%. [11,45]

1. Reorientation and Cognitive Engagement

• Frequent reorientation: Remind patient of name, date, location, and purpose of being in hospital.
• Visible clocks and calendars: Large, easy-to-read.
• Familiar objects: Family photos, personal items from home.
• Consistent staff: Minimise handovers and unfamiliar faces.
• Regular communication: Short, simple sentences. Allow time for response.

2. Optimise Sensory Function

• Vision: Clean glasses, ensure adequate lighting, avoid glare.
• Hearing: Working hearing aids (check batteries), reduce background noise, speak clearly and face the patient.

3. Normalise Sleep-Wake Cycle

• Natural light exposure: Open curtains during day, bright lighting in morning.
• Darkness at night: Dim lights, quiet ward environment.
• Minimise night disturbance: Cluster care activities, avoid waking for routine observations if stable.
• Avoid daytime napping: Encourage activity during the day.

4. Early Mobilisation

• Get patient out of bed: Chair for meals, walk to bathroom.
• Physiotherapy input: Daily mobilisation, strength and balance exercises.
• Remove physical restraints: Lines, catheters, bed rails (if safe to do so). Restraints worsen agitation and delirium. [46]

5. Nutrition and Hydration

• Encourage oral intake: Assistance with feeding if needed.
• Dentures: Ensure patient has dentures for eating.
• Dehydration: IV fluids if oral intake inadequate (target urine output 0.5 mL/kg/h).

6. Involve Family and Carers

• Family presence: Familiar faces are reassuring. Allow flexible visiting.
• Educate family: Explain that confusion is temporary, avoid arguing with patient, provide reassurance.
• "This is Me" document: NHS tool documenting patient's preferences, routines, and background (helpful for nursing staff).

7. Reduce Environmental Stressors

• Quiet side room: If available (but weigh against isolation and reduced observation).
• Minimise ward noise: Reduce alarms, staff conversations, television volume.
• Avoid ward moves: Keep patient in same bed if possible.

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Medication Review (Critical)

Stop or reduce deliriogenic medications:

Anticholinergic Burden: Many drugs have cumulative anticholinergic effects. The Anticholinergic Cognitive Burden (ACB) Scale scores medications 1-3 based on anticholinergic activity. Total ACB score 3 is associated with increased delirium risk. [47]

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Pharmacological Management (Last Resort)

Indications (use only when essential):

• Patient poses immediate risk to self or others (e.g., pulling out life-sustaining devices, aggression toward staff/patients).
• Severe distress unresponsive to non-pharmacological measures.

Caution: Antipsychotics do NOT treat delirium. They sedate the patient. They do NOT shorten delirium duration or improve outcomes. Evidence shows no benefit and possible harm (increased mortality, stroke, extrapyramidal side effects). [29,44]

Choice of Agent

1. Haloperidol (First-Line for Hyperactive Delirium)

Dose: 0.5mg PO/IM (elderly), up to 1-2mg in younger or more agitated patients. Repeat after 30-60 minutes if needed. Maximum 5mg/24h in elderly.

Mechanism: Dopamine D2 antagonist. Reduces psychomotor agitation and hallucinations.

Contraindications:

• Parkinson's disease or Lewy body dementia (risk of severe, irreversible parkinsonism).
• Prolonged QT interval (measure QTc before administration; avoid if QTc 500 ms).
• Recent stroke or seizure history.

Adverse effects:

• Extrapyramidal side effects (dystonia, parkinsonism, akathisia).
• Sedation, hypotension.
• QT prolongation → torsades de pointes.
• Neuroleptic malignant syndrome (rare but life-threatening).

2. Lorazepam (Use in Specific Situations)

Dose: 0.5mg PO/IM (elderly), up to 1-2mg in younger patients. Can repeat after 4-6 hours.

Indications:

• Parkinson's disease or Lewy body dementia (avoid haloperidol).
• Alcohol or benzodiazepine withdrawal (GABA agonist treats withdrawal).
• Seizure risk (anticonvulsant properties).
• Prolonged QT (no QT prolongation).

Caution: Paradoxical agitation, respiratory depression, worsening confusion. Use lowest dose and monitor closely.

3. Avoid Routine Use of:

• Quetiapine: Sedating, anticholinergic, not superior to haloperidol.
• Olanzapine: Anticholinergic, metabolic side effects.
• Risperidone: Increased stroke risk in elderly, extrapyramidal side effects.
• Benzodiazepines (except specific indications above): Worsen delirium, respiratory depression, falls.

Monitoring After Sedation

• Continuous observation: 1:1 nursing if possible.
• Vital signs: Every 15 minutes initially (BP, HR, RR, O2 sats).
• Review response: Reduce or stop medication as soon as agitation settles.
• Daily review: Is sedation still needed? Can dose be reduced?

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Special Populations

Delirium in Parkinson's Disease or Lewy Body Dementia

Avoid typical antipsychotics (haloperidol, risperidone) → risk of severe, irreversible parkinsonism and neuroleptic malignant syndrome.

If sedation essential:

• Lorazepam 0.5mg PO (first-line).
• Quetiapine 12.5-25mg PO (atypical with lowest risk of extrapyramidal effects, but still some risk).
• Specialist advice: Involve neurology or geriatrics.

Delirium in Alcohol Withdrawal

Treat with benzodiazepines (e.g., chlordiazepoxide or lorazepam) as per alcohol withdrawal protocol. Do NOT use haloperidol alone (lowers seizure threshold).

Add IV Pabrinex (thiamine) to prevent Wernicke's encephalopathy.

Delirium in Palliative Care

Common in terminal illness (40-88%). Treat reversible causes if appropriate. If comfort-focused:

• Haloperidol 0.5-1mg SC PRN for distressing agitation or hallucinations.
• Midazolam SC infusion if dying and agitated (palliative sedation).
• Involve specialist palliative care team.

Post-operative Delirium

Prevention: Regional anaesthesia (where possible), minimise opiates, early mobilisation, avoid anticholinergics, optimise pain control.

Management: As above. Ensure adequate analgesia (uncontrolled pain is a major precipitant).

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11. Complications

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12. Prognosis and Outcomes

Resolution Time

• Median duration: 7-10 days (with treatment of underlying cause).
• Range: Hours to weeks. Some patients take months to return to baseline.
• Hypoactive delirium: Often takes longer to resolve than hyperactive.

Educate family: "Delirium does not disappear the moment the antibiotics start. Confusion is often the last symptom to improve."

Long-Term Cognitive Outcomes

• Persistent cognitive impairment: 30-50% of delirious patients have cognitive deficits at 6 months. [48]
• Accelerated dementia: Delirium is associated with increased risk of incident dementia (3-fold increased risk) and faster cognitive decline in those with pre-existing dementia. [49]
• Mechanism: Possible neuronal injury, neuroinflammation, or "unmasking" of subclinical dementia.

Functional Outcomes

• Loss of independence: 30-50% of patients who develop delirium are unable to return home and require long-term care. [50]
• Increased dependency: Reduced activities of daily living (ADLs) and instrumental ADLs.

Recurrence Risk

• High risk of future delirium: 30-40% of patients experience recurrent delirium during subsequent hospitalisations. [51]
• Prevention strategies: Avoid deliriogenic medications, early mobilisation, maintain sensory function, treat infections promptly.

Mortality

• In-hospital mortality: 10-15% (2-fold higher than non-delirious patients). [8]
• 1-year mortality: 35-40%. [23]

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13. Prevention Strategies

Primary Prevention (High-Risk Patients)

Target patients: Age 65, dementia, frailty, hip fracture, ICU admission, major surgery.

Multicomponent Intervention Bundles

Based on the Hospital Elder Life Program (HELP). [11,45]

Evidence: HELP reduces delirium incidence by 40% and saves costs through shorter length of stay and fewer complications. [43]

Pharmacological Prevention

No evidence for routine use of antipsychotics or benzodiazepines for delirium prevention. These may cause harm. [52]

Exception: Some evidence for low-dose haloperidol (0.5mg BD) in hip fracture patients, but not recommended in guidelines due to inconsistent benefit and risk of adverse effects. [53]

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14. Key Guidelines and Evidence

NICE Clinical Guideline (CG103): Delirium

Published: 2010 (Updated 2019)

Key Recommendations:

1. Identify patients at high risk and implement multicomponent prevention strategies.
2. Use validated tools (4AT, CAM) for screening.
3. Treat underlying causes urgently.
4. Non-pharmacological interventions are first-line.
5. Avoid antipsychotics unless essential (risk to self/others or severe distress).
6. If antipsychotics used: haloperidol or olanzapine, lowest dose, shortest duration.
7. Monitor for adverse effects and review daily.

American Geriatrics Society (AGS) Guidelines

Recommendation: Avoid antipsychotics for behavioural symptoms of delirium unless non-pharmacological measures have failed and patient is a danger to self or others (Choosing Wisely). [54]

Landmark Studies

1. Inouye et al. (1999): Hospital Elder Life Program (HELP)

Design: Prospective controlled trial (852 patients).

Intervention: Multicomponent delirium prevention programme.

Results:

• 40% reduction in delirium incidence (9.9% vs 15%, p=0.02).
• Reduced delirium duration.
• Cost-effective (saved hospital costs through reduced complications and length of stay).

Impact: Established multicomponent interventions as gold standard for delirium prevention. [11]

2. Bellelli et al. (2014): Hypoactive Delirium and Mortality

Design: Prospective cohort (1867 older patients).

Results:

• Hypoactive delirium associated with higher mortality than hyperactive or mixed subtypes (HR 2.5 vs 1.5).
• Hypoactive delirium frequently missed and diagnosed later.

Impact: Highlighted importance of screening for hypoactive delirium. [15]

3. Marcantonio et al. (2001): Post-operative Delirium Prevention

Design: RCT (126 hip fracture patients).

Intervention: Proactive geriatrics consultation (daily visits targeting delirium risk factors).

Results:

• 40% reduction in severe delirium (32% vs 50%, p=0.04).
• Reduced length of stay.

Impact: Demonstrated benefit of geriatrician involvement in high-risk surgical patients. [55]

4. Girard et al. (2010): Haloperidol for Delirium Treatment

Design: RCT (101 ICU patients with delirium).

Intervention: Haloperidol vs ziprasidone vs placebo.

Results: No difference in delirium-free days, mortality, or cognitive outcomes.

Impact: Antipsychotics do NOT shorten delirium duration or improve outcomes. [29]

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15. Examination Focus

Common MRCP/FRACP Written Exam Questions

1. "Which is the strongest risk factor for delirium?"

   • Answer: Pre-existing dementia (RR 5.2). [24]

2. "What is the first-line treatment for delirium?"

   • Answer: Identify and treat the underlying cause + non-pharmacological interventions. NOT antipsychotics.

3. "An 80-year-old with Parkinson's disease develops agitation post-operatively. What is the safest sedative?"

   • Answer: Lorazepam 0.5mg PO/IM (avoid haloperidol in Parkinson's/Lewy body dementia).

4. "Which subtype of delirium has the worst prognosis?"

   • Answer: Hypoactive delirium (often missed, higher mortality). [15]

5. "What bedside test is most sensitive for delirium?"

   • Answer: Months of the year backwards (tests attention—the hallmark feature).

6. "A patient develops delirium on the ward. What is the MOST important step?"

   • Answer: Identify and treat the precipitating cause (PINCH ME screen).

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Common OSCE/PACES Scenarios

Station 1: "Assess this confused 85-year-old on the ward"

Approach:

1. Introduction and consent.
2. Collateral history (nurse/family): Baseline function? Onset? Fluctuation?
3. Screening tool: 4AT (Alertness, AMT4, Attention, Acute change).
4. Brief cognitive assessment: Orientation (time, place), attention (months backwards), memory.
5. Identify precipitants: PINCH ME (Pain? Infection? Nutrition? Constipation? Hydration? Medications? Environment?).
6. Explain to examiner: "This patient has delirium based on acute onset, inattention, and fluctuating course. I would investigate for precipitating causes and implement non-pharmacological interventions."

Model opening statement: "Delirium is an acute, fluctuating disturbance of consciousness and cognition. It is common, affecting 20% of hospital admissions, and is associated with increased mortality and morbidity. My approach is to confirm the diagnosis, identify the underlying cause, and implement multicomponent interventions."

Station 2: "This patient is agitated and pulling out lines. How do you manage?"

Approach:

1. Safety first: Ensure staff and patient safety (remove dangerous objects, 1:1 supervision).
2. ABCDE assessment: Hypoxia? Hypoglycaemia? Acute deterioration?
3. Verbal de-escalation: Calm, reassuring tone. Avoid restraint.
4. Non-pharmacological: Reorientate, involve family, reduce environmental stimuli.
5. Pharmacological (if essential): "If non-pharmacological measures fail and the patient poses immediate risk to self or others, I would consider haloperidol 0.5-1mg PO or IM, after checking for contraindications (Parkinson's, prolonged QT). I would use the lowest effective dose and review after 30-60 minutes."

Pitfall to avoid: Do NOT say "I would sedate the patient." Examiners want to hear systematic risk assessment, non-pharmacological strategies first, and judicious pharmacology as last resort.

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Viva Voce Points

Opening Statement

"Delirium, also known as acute confusional state, is an acute disturbance of consciousness, attention, and cognition that develops over hours to days and fluctuates throughout the day. It affects approximately 20% of general hospital admissions and is associated with doubled mortality. The hallmark feature is inattention. It is a clinical diagnosis based on DSM-5 criteria, and screening tools such as the 4AT aid recognition."

High-Yield Facts to Mention

• Subtypes: Hyperactive (25-30%, easy to spot), hypoactive (25-30%, frequently missed, worse outcomes), and mixed (40-50%).
• Strongest risk factor: Pre-existing dementia (RR 5.2). [24]
• Prevention: Multicomponent interventions (HELP) reduce incidence by 40%. [11]
• Treatment: Non-pharmacological first (reorientation, mobilisation, sleep hygiene). Antipsychotics do NOT shorten duration or improve outcomes. [29]
• Hypoactive trap: "The quiet patient may be the sickest." Always screen.
• Anticholinergic burden: Cumulative effect of medications (ACB scale 3 increases risk). [47]

Common Viva Questions

"What is the pathophysiology of delirium?"

• Multifactorial: Cholinergic deficiency (anticholinergic drugs precipitate), dopaminergic excess (hallucinations/agitation), neuroinflammation (peripheral cytokines cross blood-brain barrier), oxidative stress, and HPA axis dysregulation. Final result is widespread cortical and subcortical dysfunction. [26]

"How do you differentiate delirium from dementia?"

• Onset: Acute (hours-days) vs chronic (months-years).
• Course: Fluctuating vs progressive.
• Attention: Impaired (hallmark of delirium) vs intact (early dementia).
• Consciousness: Altered vs clear.
• Caveat: Dementia is the strongest risk factor for delirium. The two frequently coexist.

"What is the evidence for antipsychotics in delirium?"

• No RCT evidence that antipsychotics shorten delirium duration or improve outcomes. Girard et al. (2010) showed no benefit of haloperidol vs placebo in ICU delirium. [29] NICE guidelines recommend avoiding antipsychotics unless essential (risk to self/others). Use lowest dose, shortest duration.

"Describe the 4AT."

• Rapid (< 2 min) bedside tool. Four components: Alertness (observe for drowsiness/agitation), AMT4 (age, DOB, place, year), Attention (months backwards), Acute change or fluctuation. Score ≥4 indicates probable delirium. Sensitivity 90%, specificity 84%. [37]

"What is Wernicke's encephalopathy?"

• Acute confusional state due to thiamine (B1) deficiency. Classic triad: confusion, ataxia, ophthalmoplegia. Risk factors: alcohol excess, malnutrition, prolonged fasting. Management: Immediate IV thiamine (Pabrinex) before glucose (glucose can precipitate Wernicke's if thiamine-depleted). Prevent progression to Korsakoff syndrome (irreversible amnesia). [42]

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16. Common Pitfalls and Mistakes

❌ Mistake 1: "The urine dipstick is positive, so it must be a UTI causing delirium."

Reality: 50% of elderly women have asymptomatic bacteriuria (bacteria in urine without infection). Positive dipstick does NOT prove UTI is the cause.

Correct approach: Look for systemic features (fever, dysuria, raised CRP/WCC). Treat UTI only if clinically indicated. Always search for alternative causes.

❌ Mistake 2: "Patient is agitated, give haloperidol."

Reality: Antipsychotics do NOT treat delirium. They sedate the patient. They do NOT shorten duration or improve outcomes and carry risk of harm.

Correct approach: Identify and treat underlying cause. Non-pharmacological interventions first. Antipsychotics only if patient poses immediate risk to self or others, and after ruling out contraindications.

❌ Mistake 3: "Patient has dementia, so confusion is expected."

Reality: Patients with dementia can develop superimposed delirium. Always ask: "Is this worse than their baseline?"

Correct approach: Collateral history from family/carers. Compare current state to pre-admission baseline. Screen with 4AT.

❌ Mistake 4: "Patient is sleeping quietly, so they're improving."

Reality: Hypoactive delirium is frequently missed. Reduced activity and drowsiness may indicate worsening delirium, not improvement.

Correct approach: Serial screening (4AT, CAM). Assess attention and cognition, not just behaviour.

❌ Mistake 5: "CT head is normal, so it's not organic."

Reality: Delirium is a clinical diagnosis. Normal CT does not exclude delirium (most causes are metabolic, infectious, or drug-related, not structural).

Correct approach: Clinical diagnosis based on DSM-5 criteria. Investigate for metabolic and infectious causes (bloods, CXR, urine).

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17. Patient and Layperson Explanation

"Why is my father confused?"

"Your father has developed what we call delirium, which is like 'acute brain failure.' Just as a chest infection can make the lungs struggle to breathe, this illness has put stress on the brain, causing confusion. It's very common in hospital, especially in older people, and it's usually temporary."

"Is this dementia?"

"Delirium and dementia are different. Dementia is a slow, permanent loss of memory that develops over months or years. Delirium is a sudden, temporary reaction to illness that develops over hours or days. However, people who already have some memory loss are more likely to develop delirium. We will need to reassess his memory after he recovers to see if there is any underlying dementia."

"How long will the confusion last?"

"Delirium usually starts to improve once we treat the underlying cause—such as the infection or dehydration. However, confusion is often the last symptom to get better. It can take days to weeks for the brain to fully recover. Some people take longer, especially if they are very frail or have other health problems."

"Can we give him something to calm him down?"

"We try to avoid sedatives because they often make confusion worse, not better. Instead, we use 'natural' methods—making sure he has his glasses and hearing aids, keeping the environment calm and familiar, having family visit, and helping him understand where he is. We only use sedative medication if absolutely necessary for safety."

"Will he recover fully?"

"Most people do recover from delirium, especially if we can treat the underlying cause. However, delirium can sometimes 'unmask' memory problems that were already starting. We will reassess his memory and thinking after he recovers and make a plan for support at home if needed."

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18. References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. Washington, DC: American Psychiatric Publishing; 2013.

2. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922. doi:10.1016/S0140-6736(13)60688-1

3. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing. 2006;35(4):350-364. doi:10.1093/ageing/afl005

4. Bruce AJ, Ritchie CW, Blizard R, Lai R, Raven P. The incidence of delirium associated with orthopedic surgery: a meta-analytic review. Int Psychogeriatr. 2007;19(2):197-214. doi:10.1017/S104161020600425X

5. Collins N, Blanchard MR, Tookman A, Sampson EL. Detection of delirium in the acute hospital. Age Ageing. 2010;39(1):131-135. doi:10.1093/ageing/afp201

6. Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304(4):443-451. doi:10.1001/jama.2010.1013

7. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012;367(1):30-39. doi:10.1056/NEJMoa1112923

8. McAvay GJ, Van Ness PH, Bogardus ST Jr, et al. Older adults discharged from the hospital with delirium: 1-year outcomes. J Am Geriatr Soc. 2006;54(8):1245-1250. doi:10.1111/j.1532-5415.2006.00815.x

9. National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. Clinical guideline [CG103]. Published July 2010. Updated March 2019. https://www.nice.org.uk/guidance/cg103

10. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996;275(11):852-857.

11. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676. doi:10.1056/NEJM199903043400901

12. Meagher DJ, Leonard M, Donnelly S, Conroy M, Adamis D, Trzepacz PT. A longitudinal study of motor subtypes in delirium: frequency and stability during episodes. J Psychosom Res. 2012;72(3):236-241. doi:10.1016/j.jpsychores.2011.11.013

13. Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Am J Psychiatry. 2014;171(2):151-159. doi:10.1176/appi.ajp.2013.13040458

14. Hustey FM, Meldon SW, Smith MD, Lex CK. The effect of mental status screening on the care of elderly emergency department patients. Ann Emerg Med. 2003;41(5):678-684. doi:10.1067/mem.2003.152

15. Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014;43(4):496-502. doi:10.1093/ageing/afu021

16. Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc. 2006;54(3):479-484. doi:10.1111/j.1532-5415.2005.00621.x

17. Ryan DJ, O'Regan NA, Caoimh RÓ, et al. Delirium in an adult acute hospital population: predictors, prevalence and detection. BMJ Open. 2013;3(1):e001772. doi:10.1136/bmjopen-2012-001772

18. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-1762. doi:10.1001/jama.291.14.1753

19. Dasgupta M, Dumbrell AC. Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc. 2006;54(10):1578-1589. doi:10.1111/j.1532-5415.2006.00893.x

20. Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Arch Intern Med. 2000;160(6):786-794. doi:10.1001/archinte.160.6.786

21. Han JH, Zimmerman EE, Cutler N, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16(3):193-200. doi:10.1111/j.1553-2712.2008.00339.x

22. Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008;168(1):27-32. doi:10.1001/archinternmed.2007.4

23. Kiely DK, Marcantonio ER, Inouye SK, et al. Persistent delirium predicts greater mortality. J Am Geriatr Soc. 2009;57(1):55-61. doi:10.1111/j.1532-5415.2008.02092.x

24. Fong TG, Jones RN, Shi P, et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570-1575. doi:10.1212/WNL.0b013e3181a4129a

25. Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009;37(1):177-183. doi:10.1097/CCM.0b013e318192fcf9

26. Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190-1222. doi:10.1016/j.jagp.2013.09.005

27. Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry. 2001;62 Suppl 21:11-14.

28. Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001;13(2):229-242. doi:10.1176/jnp.13.2.229

29. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010;38(2):428-437. doi:10.1097/CCM.0b013e3181c58715

30. van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet. 2010;375(9716):773-775. doi:10.1016/S0140-6736(09)61158-2

31. Cunningham C, Maclullich AM. At the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response. Brain Behav Immun. 2013;28:1-13. doi:10.1016/j.bbi.2012.07.012

32. de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res. 2007;62(5):521-525. doi:10.1016/j.jpsychores.2006.11.013

33. Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010;119(6):737-754. doi:10.1007/s00401-010-0674-1

34. Pearson A, de Vries A, Middleton SD, et al. Cerebrospinal fluid cortisol levels are higher in patients with delirium versus controls. BMC Res Notes. 2010;3:33. doi:10.1186/1756-0500-3-33

35. O'Keeffe ST, Lavan JN. Clinical significance of delirium subtypes in older people. Age Ageing. 1999;28(2):115-119. doi:10.1093/ageing/28.2.115

36. Shenkin SD, Fox C, Godfrey M, et al. Delirium detection in older acute medical inpatients: a multicentre prospective comparative diagnostic test accuracy study of the 4AT and the confusion assessment method. BMC Med. 2019;17(1):138. doi:10.1186/s12916-019-1367-9

37. Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014;43(4):496-502. doi:10.1093/ageing/afu021

38. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113(12):941-948. doi:10.7326/0003-4819-113-12-941

39. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;29(7):1370-1379. doi:10.1097/00003246-200107000-00012

40. Sands MB, Dantoc BP, Hartshorn A, Ryan CJ, Lujic S. Single Question in Delirium (SQiD): testing its efficacy against psychiatrist interview, the Confusion Assessment Method and the Memorial Delirium Assessment Scale. Palliat Med. 2010;24(6):561-565. doi:10.1177/0269216310371556

41. Sutter R, Kaplan PW. Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey. Epilepsia. 2012;53 Suppl 3:1-51. doi:10.1111/j.1528-1167.2012.03593.x

42. Thomson AD, Marshall EJ, Bell D. Time to act on the inadequate management of Wernicke's encephalopathy in the UK. Alcohol Alcohol. 2013;48(1):4-8. doi:10.1093/alcalc/ags116

43. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med. 2015;175(4):512-520. doi:10.1001/jamainternmed.2014.7779

44. Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev. 2007;(2):CD005594. doi:10.1002/14651858.CD005594.pub2

45. Rubin FH, Williams JT, Lescisin DA, Mook WJ, Hassan S, Inouye SK. Replicating the Hospital Elder Life Program in a community hospital and demonstrating effectiveness using quality improvement methodology. J Am Geriatr Soc. 2006;54(6):969-974. doi:10.1111/j.1532-5415.2006.00744.x

46. Mott S, Poole J, Kenrick M. Physical and chemical restraints in acute care: their potential impact on the rehabilitation of older people. Int J Nurs Pract. 2005;11(3):95-101. doi:10.1111/j.1440-172X.2005.00510.x

47. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168(5):508-513. doi:10.1001/archinternmed.2007.106

48. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-1520. doi:10.1097/CCM.0b013e3181e47be1

49. Davis DH, Muniz Terrera G, Keage H, et al. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain. 2012;135(Pt 9):2809-2816. doi:10.1093/brain/aws190

50. Murray AM, Levkoff SE, Wetle TT, et al. Acute delirium and functional decline in the hospitalized elderly patient. J Gerontol. 1993;48(5):M181-186. doi:10.1093/geronj/48.5.m181

51. Rockwood K, Cosway S, Carver D, Jarrett P, Stadnyk K, Fisk J. The risk of dementia and death after delirium. Age Ageing. 1999;28(6):551-556. doi:10.1093/ageing/28.6.551

52. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705-714. doi:10.1111/jgs.14076

53. Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med. 2012;40(3):731-739. doi:10.1097/CCM.0b013e3182376e4f

54. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi:10.1111/jgs.13702

55. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49(5):516-522. doi:10.1046/j.1532-5415.2001.49108.x

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