Delirium in ICU

Quick Answer

Delirium is an acute fluctuating disturbance of consciousness and cognition affecting 30-50% of ICU patients (70-80% of mechanically ventilated patients). [1,2] Screen using CAM-ICU (sensitivity 80%, specificity 96%). [3] Implement the ABCDEF bundle: (A) Assess pain, (B) Both SAT/SBT, (C) Choice of sedation (avoid benzodiazepines), (D) Delirium assessment, (E) Early mobility, (F) Family engagement. [4,5] Three subtypes: hyperactive (agitated), hypoactive (most common, often missed), and mixed. [6] Delirium duration independently predicts long-term cognitive impairment similar to traumatic brain injury or mild Alzheimer's disease. [7] First-line management: treat underlying causes, non-pharmacological interventions (reorientation, sleep hygiene, early mobilization). [8] Antipsychotics (haloperidol, quetiapine) do NOT reduce delirium duration or improve mortality but may control agitation. [9,10] Dexmedetomidine reduces delirium incidence compared to benzodiazepines. [11,12]

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CICM Exam Focus

Second Part Written

High-Yield Topics:

• CAM-ICU scoring system and interpretation (Feature 1-4 assessment)
• ABCDEF bundle components and evidence base
• Risk factors: predisposing (age, dementia, comorbidity) vs precipitating (benzodiazepines, sepsis, metabolic)
• Subtypes: hyperactive, hypoactive, mixed - recognition and implications
• Pathophysiology: cholinergic deficiency, dopamine excess, neuroinflammation
• Pharmacological management: antipsychotics (lack of efficacy for duration/mortality), dexmedetomidine
• Non-pharmacological strategies: early mobility, sleep hygiene, family engagement
• Long-term outcomes: PICS, cognitive impairment, mortality

Common SAQ Themes:

• "Discuss the assessment and management of delirium in a ventilated ICU patient"
• "Compare CAM-ICU and ICDSC delirium screening tools"
• "Outline the ABCDEF bundle and supporting evidence"
• "What is the role of antipsychotics in ICU delirium?"

Viva Voce

Expect Questions On:

• Walk through CAM-ICU assessment at bedside
• Differentiate delirium subtypes clinically
• Justify sedation choices (dexmedetomidine vs propofol vs benzodiazepines)
• Explain why haloperidol trials were negative despite widespread use
• Discuss the link between delirium duration and long-term cognitive outcomes
• Describe the ICU Liberation Campaign and bundle compliance data

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Key Points

Definition and Classification

1. DSM-5 Criteria: Acute disturbance in attention and awareness that develops over hours to days and fluctuates in severity. [13]

2. Subtypes: [6]

   • Hyperactive (15-25%): Agitation, restlessness, combativeness, emotional lability
   • Hypoactive (50-60%): Lethargy, reduced responsiveness, withdrawal (most common, frequently missed)
   • Mixed (20-30%): Fluctuates between hyperactive and hypoactive

3. Subsyndromal Delirium (SSD): Presence of delirium symptoms not meeting full criteria; associated with worse outcomes and increased risk of progressing to full delirium. [14]

Epidemiology

1. Incidence: [1,2]

   • General ICU patients: 30-50%
   • Mechanically ventilated patients: 70-80%
   • Cardiac surgery: 15-50%
   • Medical ICU vs Surgical ICU: Higher in medical populations

2. Impact on Outcomes: [7,15]

   • Increased hospital mortality (2-4 fold)
   • Prolonged mechanical ventilation (median increase 2-3 days)
   • Increased ICU and hospital length of stay
   • Higher risk of long-term cognitive impairment (30-50% at 3-12 months)
   • Increased healthcare costs

Pathophysiology

1. Neurotransmitter Imbalance: [16,17]

   • Cholinergic deficiency: Reduced acetylcholine (ACh) impairs attention, memory, sleep-wake cycle
   • Dopamine excess: Hyperdopaminergic state contributes to agitation, psychosis
   • GABA dysfunction: Altered GABAergic transmission
   • Serotonin dysregulation

2. Neuroinflammation: [18]

   • Systemic inflammation (sepsis, surgery) crosses blood-brain barrier
   • Cytokine release (IL-1, IL-6, TNF-α) → microglial activation
   • Oxidative stress and neuronal damage
   • Increased acetylcholinesterase activity → further ACh depletion

3. Cerebral Dysfunction: [19]

   • Reduced cerebral blood flow and metabolism
   • Blood-brain barrier disruption
   • Neuronal apoptosis in hippocampus and prefrontal cortex
   • EEG: Diffuse slowing, loss of alpha rhythm

4. Circadian Rhythm Disruption: [20]

   • Sleep-wake cycle fragmentation
   • Reduced REM and deep sleep
   • ICU noise levels: 60-80 dB (WHO recommends below 35 dB for sleep)

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Clinical Presentation

Risk Factors

Predisposing Factors (Non-modifiable): [2,21]

• Advanced age (greater than 65 years) - strongest risk factor
• Pre-existing cognitive impairment or dementia
• History of alcohol abuse
• High baseline illness severity (APACHE II, SOFA scores)
• Visual or hearing impairment
• Multiple comorbidities (hypertension, diabetes, heart failure)

Precipitating Factors (Modifiable): [2,21]

• Medications: Benzodiazepines (strongest association), anticholinergics, opioids (high doses)
• Mechanical ventilation
• Sepsis/infection
• Metabolic disturbances: Hypoglycemia, electrolyte imbalance, hypoxia, hypercapnia
• Sleep deprivation
• Physical restraints
• Immobility
• Pain (undertreated)
• Organ dysfunction: Hepatic encephalopathy, uremia

Clinical Features by Subtype

Hyperactive Delirium (15-25%): [6]

• Agitation, restlessness, combativeness
• Pulling at lines/tubes
• Emotional lability, irritability
• Hypervigilance
• Hallucinations (visual > auditory)
• Sleep-wake cycle reversal
• Often RASS +1 to +4

Hypoactive Delirium (50-60%): [6]

• Most common but most frequently missed
• Lethargy, reduced responsiveness
• Apathy, withdrawal
• Decreased motor activity
• Flat affect
• Often mistaken for sedation or depression
• Often RASS -1 to -3 (but arousable)
• Associated with worse prognosis than hyperactive

Mixed Delirium (20-30%): [6]

• Fluctuates between hyperactive and hypoactive states
• May change hour-to-hour or day-to-day

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Assessment and Screening

CAM-ICU (Confusion Assessment Method for ICU)

Gold Standard Screening Tool [3,22]

• Sensitivity: 80% (range 76-95%)
• Specificity: 96% (range 89-100%)
• Can be performed in intubated and non-intubated patients
• Requires RASS ≥ -3 (patient must be arousable)

Four Features: [3,22]

Feature 1: Acute Onset or Fluctuating Course

• Is there an acute change from baseline mental status?
• OR has behavior fluctuated during the past 24 hours?

Feature 2: Inattention

• Assessed using Auditory or Visual tests:
  • Auditory: "Squeeze my hand when I say the letter A" (SAVEAHAART - 10 letters, 3 target A's)
  • "Visual: Show pictures and ask patient to identify specific ones"
• Positive if greater than 2 errors

Feature 3: Altered Level of Consciousness

• Current RASS score other than zero (alert and calm)
• RASS +1 to +4 or RASS -1 to -3

Feature 4: Disorganized Thinking

• Four Yes/No questions:
  1. "Will a stone float on water?"
  2. "Are there fish in the sea?"
  3. "Does one pound weigh more than two pounds?"
  4. "Can you use a hammer to pound a nail?"
• Plus command: "Hold up this many fingers" (examiner holds up 2), then "Now do the same thing with the other hand" (without repeating the number)
• Positive if greater than 1 error

CAM-ICU Positive = Features 1 AND 2 AND (3 OR 4)

ICDSC (Intensive Care Delirium Screening Checklist)

Alternative Screening Tool [23]

• 8-point checklist scored 0-8
• Score ≥4 = delirium
• Easier to use than CAM-ICU but less specific
• Can detect subsyndromal delirium (score 1-3)

Checklist Items (1 point each):

1. Altered level of consciousness (RASS other than 0)
2. Inattention
3. Disorientation (time, place, person)
4. Hallucination, delusion, psychosis
5. Psychomotor agitation or retardation
6. Inappropriate speech or mood
7. Sleep-wake cycle disturbance
8. Symptom fluctuation

Comparison CAM-ICU vs ICDSC: [24]

• CAM-ICU: Higher specificity (96% vs 87%), better for research, requires training
• ICDSC: Higher sensitivity for subsyndromal delirium, easier implementation, better for continuous monitoring

RASS (Richmond Agitation-Sedation Scale)

Essential Prerequisite for CAM-ICU [25]

For CAM-ICU: Patient must be RASS ≥ -3 (arousable to voice)

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Investigations

Clinical Assessment

Primary Goals:

1. Screen for delirium (CAM-ICU or ICDSC)
2. Identify and treat underlying causes
3. Assess for complications

Initial Workup: [26]

• Full blood count (infection, anemia)
• Electrolytes, renal function (uremia, electrolyte disturbance)
• Liver function tests (hepatic encephalopathy)
• Blood glucose (hypo/hyperglycemia)
• Blood gas analysis (hypoxia, hypercapnia, acidosis)
• Blood cultures if sepsis suspected
• Urinalysis and culture (urinary tract infection)
• Medication review (anticholinergic burden, benzodiazepines)

Further Investigations (if indicated):

• CT head: If concern for intracranial pathology (stroke, hemorrhage, mass)
• Lumbar puncture: If meningoencephalitis suspected
• EEG: If concern for non-convulsive seizures (rare indication)
• Thyroid function: If metabolic encephalopathy unclear
• Ammonia level: If hepatic encephalopathy suspected
• Vitamin B12, thiamine: If nutritional deficiency suspected

Predictive Models

PRE-DELIRIC (PREdiction of DELIRium in ICU patients) [27]

• 10-variable prediction model
• Developed and validated in Dutch ICUs
• AUC 0.77 (good discrimination)
• Variables include: age, APACHE II, admission category, infection, metabolic acidosis, sedation, morphine use, urea, urgency

E-PRE-DELIRIC (Early PREdiction): [28]

• Can be calculated within 24 hours of ICU admission
• Uses 9 variables available at admission
• AUC 0.76

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Management

Non-Pharmacological Interventions (FIRST-LINE)

ABCDEF Bundle (ICU Liberation Campaign) [4,5,29]

Evidence: High bundle compliance associated with: [4]

• 68% reduction in likelihood of death
• 25-50% reduction in delirium duration
• Shorter mechanical ventilation (median 2-3 days)
• More discharges to home rather than rehabilitation

A: Assess, Prevent, and Manage Pain [30]

• Use validated pain scales:
  • "BPS (Behavioral Pain Scale): For intubated patients unable to self-report"
  • "CPOT (Critical-Care Pain Observation Tool): Alternative validated tool"
  • "Numeric Rating Scale: For communicative patients"
• Multimodal analgesia (reduce opioid dose)
• Treat pain BEFORE sedating

B: Both SAT and SBT Coordination [31]

• Spontaneous Awakening Trial (SAT): Daily interruption of sedation (unless contraindicated)
• Spontaneous Breathing Trial (SBT): Test readiness for extubation
• Coordinate SAT and SBT: Perform together when patient passes SAT safety screen
• Evidence: Reduces delirium, ventilator days, mortality

C: Choice of Analgesia and Sedation [11,12,32]

• AVOID benzodiazepines (strongest modifiable risk factor for delirium)
• Preferred sedatives:
  • "Propofol: No delirium benefit vs benzodiazepines, but shorter wake-up time"
  • "Dexmedetomidine: α2-agonist, reduces delirium incidence vs benzodiazepines/propofol"
    • MENDS trial: Lower delirium vs lorazepam [11]
    • SEDCOM trial: Lower delirium vs midazolam [12]
    • Limitations: Bradycardia, hypotension, cost
• Target light sedation: RASS 0 to -1 (unless contraindicated)

D: Delirium Assessment, Prevention, and Management [2,8]

• Screen: CAM-ICU or ICDSC every 8-12 hours
• Prevent: Modify risk factors
• Treat: Non-pharmacological first, pharmacological for agitation/safety

E: Early Mobility and Exercise [33,34]

• Mobilize as soon as physiologically stable
• Levels of mobility:
  • Passive range of motion
  • Sitting at edge of bed
  • Transfer to chair
  • Ambulation (with assistance)
• Evidence: Reduces delirium duration, improves functional outcomes, reduces ICU-acquired weakness
• Barriers: Deep sedation, staff availability, safety concerns

F: Family Engagement and Empowerment [35]

• Unrestricted visiting hours (when feasible)
• Include family in multidisciplinary rounds
• Encourage family participation in reorientation
• Provide family education about delirium
• Evidence: Reduces delirium duration, reduces family anxiety, improves patient satisfaction

Other Non-Pharmacological Strategies: [8,36]

• Reorientation: Clocks, calendars, windows, family photos
• Cognitive stimulation: Conversation, reading, familiar objects
• Sleep hygiene: [37,38]
  • Earplugs (reduce delirium by ~50%, relative risk 0.59) [37,38]
  • Eye masks
  • Reduce nighttime noise (staff education, alarm management)
  • Dim lights at night, bright lights during day
  • Minimize overnight procedures/lab draws
• Sensory aids: Glasses, hearing aids
• Avoid physical restraints (use only for immediate safety)
• Music therapy: Personalized music may reduce agitation

Pharmacological Management

General Principle: Pharmacological agents do NOT reduce delirium duration or improve mortality. [9,10] Use only for symptom control when agitation poses safety risk (to patient or staff).

Antipsychotics

Haloperidol [9,39]

• Typical antipsychotic, D2 antagonist
• Dose: 0.5-2 mg IV/PO every 6-8 hours (elderly lower dose 0.25-0.5 mg)
• Maximum: 20 mg/24 hours (though usually below 10 mg total)
• Evidence:
  • "MIND-USA trial (PMID: 23842232): Haloperidol vs ziprasidone vs placebo - no difference in delirium-free days [9]"
  • "HOPE-ICU trial (PMID: 23842231): Haloperidol vs placebo - no difference in delirium duration or mortality [10]"
  • "AID-ICU trial: Haloperidol vs placebo - no improvement in delirium days or 90-day mortality [39]"
• Adverse effects:
  • QTc prolongation (monitor ECG if dose greater than 5 mg/day)
  • Extrapyramidal symptoms (rare at low doses)
  • Neuroleptic malignant syndrome (very rare)
  • Torsades de pointes (rare)
• Contraindications: Parkinson's disease, Lewy body dementia, prolonged QTc (greater than 500 ms)

Quetiapine [40]

• Atypical antipsychotic
• Dose: 12.5-50 mg PO twice daily
• Evidence: Small trials suggest may reduce delirium duration compared to placebo, but larger trials lacking
• Advantages: Less QTc prolongation than haloperidol, sedating (may improve sleep)
• Adverse effects: Sedation, hypotension, metabolic effects (less concern short-term)

Olanzapine

• Atypical antipsychotic
• Dose: 2.5-5 mg PO daily
• Evidence: Limited ICU data, some use in palliative care delirium
• Adverse effects: Similar to quetiapine

Dexmedetomidine [11,12,41]

• α2-adrenergic agonist, NOT a traditional sedative
• Indications: Sedation choice in mechanically ventilated patients, agitated delirium (especially if ventilated)
• Dose: 0.2-1.5 mcg/kg/h infusion (no loading dose for delirium treatment)
• Mechanism: Sedation via locus coeruleus (preserves more natural sleep), minimal respiratory depression
• Evidence:
  • "MENDS trial: Dexmedetomidine vs lorazepam - more delirium-free days [11]"
  • "SEDCOM trial: Dexmedetomidine vs midazolam - lower delirium prevalence [12]"
  • "DexMedetomidine to Lessen ICU Agitation (DahLIA): Dexmedetomidine reduced agitation vs placebo [41]"
• Adverse effects: Bradycardia (20-25%), hypotension (25-30%), cost
• Monitoring: Continuous ECG, BP monitoring

Agents to AVOID

Benzodiazepines [2,32]

• Strongest modifiable risk factor for delirium
• Avoid except for specific indications:
  • Alcohol withdrawal
  • Benzodiazepine withdrawal
  • Seizures
  • Specific anesthesia situations
• If required: Use shortest-acting agent (lorazepam > midazolam > diazepam for withdrawal)

Rivastigmine (Acetylcholinesterase Inhibitor) [42]

• NOT recommended
• Trial showed INCREASED mortality and longer delirium duration
• Van Eijk et al. Lancet 2010: Rivastigmine vs placebo - higher mortality, trial stopped early [42]

Melatonin/Ramelteon [43,44]

• Insufficient evidence for routine use
• Pro-MEDIC trial: Melatonin 4 mg did NOT reduce delirium prevalence [43]
• Meta-analyses: Melatonin agonists generally ineffective [44]
• May improve sleep perception but does not translate to delirium reduction
• SCCM PADIS guidelines suggest AGAINST routine use

Special Situations

Alcohol Withdrawal Delirium (Delirium Tremens) [45]

• Benzodiazepines ARE first-line for alcohol withdrawal
• CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol) protocol
• Symptom-triggered vs fixed-dose regimens
• Thiamine 100 mg IV before glucose administration (prevent Wernicke's encephalopathy)
• Adjuncts: Dexmedetomidine, phenobarbital (refractory cases)

Postoperative Delirium (Cardiac Surgery) [46]

• Incidence: 15-50% after cardiac surgery
• Risk factors: Cardiopulmonary bypass duration, intraoperative hypotension, microemboli
• Prevention: Cerebral oximetry monitoring, avoid deep sedation, early extubation protocols
• Strong predictor of postoperative cognitive dysfunction (POCD)

Hypoactive Delirium [6]

• Most commonly missed subtype
• Often mistaken for depression or appropriate sedation
• Worse prognosis than hyperactive delirium
• Requires same systematic approach (treat causes, non-pharmacological interventions)
• Avoid antipsychotics (may worsen sedation)

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Prognosis and Long-Term Outcomes

Short-Term Outcomes

Hospital Mortality [2,15]

• Delirium increases mortality 2-4 fold
• Hypoactive delirium associated with HIGHER mortality than hyperactive
• Each additional day of delirium increases mortality risk

ICU and Hospital Length of Stay [15]

• Median increase: 2-3 days ICU stay, 5-10 days hospital stay
• Increased mechanical ventilation days
• Higher rate of reintubation

Complications [2,15]

• Unplanned extubation
• Line/catheter removal
• Falls (if mobilizing)
• Pressure ulcers
• Healthcare-associated infections

Long-Term Outcomes

Post-Intensive Care Syndrome (PICS) [7,15,47]

• Physical: ICU-acquired weakness, reduced exercise tolerance
• Cognitive: Executive dysfunction, memory impairment, reduced processing speed
• Psychological: PTSD, depression, anxiety

Cognitive Impairment [7,48]

• BRAIN-ICU Study (Pandharipande et al. NEJM 2013): [7]
  • "At 3 months: 40% had cognitive scores similar to moderate traumatic brain injury"
  • 26% had scores similar to mild Alzheimer's disease
  • "At 12 months: Cognitive impairment persisted in 30-50%"
  • Delirium duration independently predicted cognitive impairment (dose-response relationship)
  • Affects BOTH elderly and young patients
• Girard et al. Crit Care Med 2010: [48]
  • Longer delirium duration → worse global cognitive scores, worse executive function
  • Each additional day of delirium associated with decreased cognitive performance

Functional Outcomes [47]

• Reduced ability to perform Activities of Daily Living (ADLs)
• Lower employment rates post-ICU
• Reduced quality of life scores
• Higher rates of institutionalization (nursing home)

Dementia Risk [49]

• Delirium increases long-term risk of developing dementia
• Uncertain whether delirium is causative or reveals underlying vulnerability

Factors Associated with Better Outcomes

Bundle Compliance [4,5]

• High ABCDEF bundle compliance → 68% reduction in mortality, shorter delirium duration

Early Delirium Resolution [48]

• Shorter delirium duration → better long-term cognitive outcomes

Delirium Prevention [8,36]

• Preventing delirium superior to treating established delirium

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Practice Questions

SAQ 1: Delirium Assessment (10 marks)

Question: A 68-year-old man is Day 3 post-coronary artery bypass grafting. He is extubated and receiving oxygen via nasal prongs. On examination, he is pulling at his IV lines and asking to "go home to feed the horses" (he lives in an apartment). His wife states he has been "not himself" since this morning. Outline your approach to delirium assessment in this patient.

Model Answer:

Definition and Recognition (2 marks)

• Acute disturbance in attention and cognition, fluctuating over hours to days
• Clinical features suggest hyperactive delirium (agitation, disorientation, inappropriate speech)
• High-risk patient: Age greater than 65, cardiac surgery, postoperative day 3

Screening Tool - CAM-ICU (4 marks)

Assess 4 features:

1. Acute onset/fluctuating course: YES - wife reports acute change since morning
2. Inattention: Test with auditory assessment (SAVEAHAART - squeeze on letter A)
   • Likely positive given pulling at lines, disorientation
3. Altered level of consciousness: Check RASS score
   • Likely RASS +1 to +2 (restless/agitated)
   • Feature positive if RASS ≠ 0
4. Disorganized thinking: Ask 4 yes/no questions + command
   • "Will a stone float on water?" (No)
   • "Are there fish in the sea?" (Yes)
   • "Does one pound weigh more than two?" (No)
   • "Can you use a hammer to pound a nail?" (Yes)
   • Command: "Hold up this many fingers" then "Do the same with other hand"
   • greater than 1 error = positive

CAM-ICU Positive if Features 1 AND 2 AND (3 OR 4)

Identify Precipitants (2 marks)

• Review medications: Opioids, benzodiazepines, anticholinergics
• Check metabolic panel: Electrolytes, renal function, glucose
• Assess for infection: Cultures if febrile
• Review pain control, sleep deprivation, sensory impairment
• Postoperative factors: Cerebral microemboli, blood loss, inflammatory response

Initial Management (2 marks)

• Non-pharmacological first-line:
  • Reorientation (clock, calendar, reassure)
  • Family presence and engagement
  • Ensure glasses/hearing aids if used
  • Optimize environment (reduce noise, normal lighting)
  • Avoid physical restraints (use sitter/family if needed)
• Treat underlying causes
• Consider antipsychotic (haloperidol 0.5 mg) ONLY if agitation poses safety risk
• Prevent complications (fall risk, line removal)

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SAQ 2: ABCDEF Bundle (10 marks)

Question: Describe the ABCDEF bundle for delirium prevention in ICU. Include the evidence supporting its use.

Model Answer:

Overview (1 mark)

• Multicomponent evidence-based intervention
• Part of ICU Liberation Campaign (Society of Critical Care Medicine)
• Aims to reduce delirium, improve survival, enhance long-term outcomes

Bundle Components (6 marks)

A: Assess, Prevent, and Manage Pain

• Use validated pain scales (BPS, CPOT for intubated; numeric scale for communicative)
• Treat pain BEFORE sedation
• Multimodal analgesia to reduce opioid dose

B: Both SAT and SBT

• SAT (Spontaneous Awakening Trial): Daily sedation interruption
• SBT (Spontaneous Breathing Trial): Test readiness for extubation
• Coordinate SAT and SBT when patient passes safety screen

C: Choice of Analgesia and Sedation

• AVOID benzodiazepines (strongest delirium risk factor)
• Prefer dexmedetomidine or propofol
• Target light sedation (RASS 0 to -1)

D: Delirium - Assess, Prevent, Manage

• Screen with CAM-ICU or ICDSC every 8-12 hours
• Non-pharmacological interventions first-line
• Identify and treat precipitants

E: Early Mobility and Exercise

• Mobilize as soon as physiologically stable
• Range of motion → sitting → standing → ambulation
• Reduces delirium duration, ICU-acquired weakness

F: Family Engagement and Empowerment

• Unrestricted visiting when feasible
• Include family in rounds and care planning
• Family participation in reorientation

Evidence Base (3 marks)

Pun et al. 2019 (ICU Liberation Collaborative) - PMID 30339549:

• Over 15,000 ICU patients
• Dose-response relationship: Higher bundle compliance → better outcomes
• 68% reduction in likelihood of death
• 25-50% reduction in delirium duration
• Shorter mechanical ventilation
• More discharges to home vs rehabilitation

Barnes-Daly et al. 2017 - PMID 28359489:

• Even partial bundle compliance improved outcomes
• Decreased hospital mortality
• More delirium-free and coma-free days

Conclusion:

• Strong evidence supporting bundle use
• Non-pharmacological, multicomponent approach superior to single interventions
• Implementation barriers: Requires multidisciplinary coordination, culture change

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SAQ 3: Pharmacological Management (10 marks)

Question: Critically evaluate the role of antipsychotic medications in the treatment of ICU delirium.

Model Answer:

Background (1 mark)

• Antipsychotics widely used despite limited evidence
• Proposed mechanism: Dopamine (D2) receptor antagonism
• Used for symptom control (agitation) rather than delirium treatment

Evidence from Clinical Trials (4 marks)

MIND-USA Trial (Page et al. 2013 - PMID 23842232):

• Haloperidol vs Ziprasidone vs Placebo
• No difference in delirium-free days between groups
• No mortality benefit

HOPE-ICU Trial (Al-Qadheeb et al. 2013 - PMID 23842231):

• Haloperidol vs Placebo
• No difference in delirium duration
• No difference in mortality

AID-ICU Trial (Andersen-Ranberg et al. 2022):

• Haloperidol vs Placebo in mechanically ventilated patients
• No improvement in delirium days
• No 90-day mortality benefit

Meta-analyses:

• Consistent finding: Antipsychotics do NOT reduce delirium duration or improve survival
• May reduce agitation symptoms

Current Recommendations (2 marks)

Society of Critical Care Medicine (SCCM) PADIS Guidelines 2018:

• DO NOT routinely use antipsychotics to treat delirium
• Consider ONLY for:
  • Safety (patient or staff at risk from agitation)
  • Symptom control when non-pharmacological measures fail

Indications (1 mark)

• Severe agitation despite non-pharmacological interventions
• Risk of harm (line removal, extubation, violence)
• Hallucinations/delusions causing distress
• NOT for routine delirium treatment or prevention

Haloperidol Dosing and Monitoring (1 mark)

• Dose: 0.5-2 mg IV/PO every 6-8 hours (lower in elderly: 0.25-0.5 mg)
• Maximum: Usually below 10 mg/24 hours
• Monitor: ECG for QTc prolongation if dose greater than 5 mg/day
• Contraindications: Parkinson's, Lewy body dementia, prolonged QTc greater than 500 ms

Adverse Effects (1 mark)

• QTc prolongation → Torsades de pointes (rare)
• Extrapyramidal symptoms (rare at low doses)
• Neuroleptic malignant syndrome (very rare)

Conclusion:

• Antipsychotics do NOT treat delirium or improve outcomes
• Use sparingly for symptom control and safety
• Non-pharmacological interventions remain first-line

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SAQ 4: Long-Term Cognitive Outcomes (10 marks)

Question: Discuss the relationship between ICU delirium and long-term cognitive impairment. Include relevant evidence.

Model Answer:

Background (1 mark)

• Post-Intensive Care Syndrome (PICS): Physical, cognitive, psychological impairments after critical illness
• Delirium duration is strongest independent predictor of long-term cognitive decline

BRAIN-ICU Study (Pandharipande et al. NEJM 2013 - PMID 24088092) (3 marks)

Design:

• Prospective multicenter cohort
• ICU survivors assessed at 3 and 12 months post-discharge
• Neuropsychological testing battery

Key Findings:

• At 3 months:
  • 40% had cognitive scores similar to moderate traumatic brain injury
  • 26% had scores similar to mild Alzheimer's disease
• At 12 months:
  • Cognitive impairment persisted in 30-50%
• Delirium duration independently predicted worse cognitive outcomes (dose-response)
• Affected BOTH elderly and young, previously healthy patients
• Sedative/analgesic dose NOT consistently associated with impairment

Cognitive Domains Affected (2 marks)

Executive Function:

• Planning, organizing, problem-solving impaired
• Difficulty multitasking

Memory:

• Short-term recall problems
• Working memory deficits

Attention and Processing Speed:

• Reduced concentration
• Slower information processing

Visuospatial Abilities:

• Difficulty with spatial navigation
• Impaired recognition of spatial relationships

Proposed Mechanisms (2 marks)

Neuroinflammation:

• Systemic inflammation crosses blood-brain barrier
• Cytokine release → microglial activation
• Persistent neuroinflammation after ICU

Oxidative Stress:

• Reactive oxygen species → neuronal damage
• Mitochondrial dysfunction

Neuronal Damage and Atrophy:

• Permanent neuronal loss in hippocampus, prefrontal cortex
• Brain volume loss demonstrated on MRI studies
• Hippocampal atrophy correlates with memory impairment

Vascular Injury:

• Microvascular thrombosis, ischemia
• Blood-brain barrier disruption

Functional Impact (1 mark)

• Reduced ability to return to work (employment rates)
• Difficulty with Instrumental Activities of Daily Living (IADLs): Managing finances, medications
• Lower quality of life scores
• Higher institutionalization rates (nursing home placement)
• Co-morbidity with PTSD, depression

Prevention Strategies (1 mark)

• ABCDEF bundle implementation reduces delirium duration
• Each day of delirium prevented → improved long-term cognition
• Early mobilization, family engagement, avoiding benzodiazepines
• Delirium prevention superior to treatment of established delirium

Conclusion:

• Delirium has devastating long-term consequences beyond ICU
• Emphasizes need for aggressive prevention strategies
• Challenges traditional ICU culture of deep sedation and immobility

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Viva Scenarios

Viva 1: CAM-ICU Assessment and Immediate Management

Scenario: You are called to review a 72-year-old woman on Day 5 of an ICU admission for community-acquired pneumonia. She was extubated yesterday. The nurse reports she is "confused and agitated," attempting to climb out of bed. She has no history of dementia. Walk me through your assessment and immediate management.

Expected Discussion Points:

Initial Assessment:

• Ensure immediate safety (fall prevention, bed rails, consider sitter)
• Quick ABCDE assessment (airway patency, respiratory distress, hemodynamic stability)
• Check RASS score (likely +1 to +3: restless to agitated)

Delirium Screening - CAM-ICU:

Feature 1: Acute onset/fluctuating course

• Ask nurse: "Is this an acute change from baseline?" (YES - extubated yesterday, now acutely confused)
• "Has her behavior fluctuated over the past 24 hours?" (likely YES)
• Feature 1: POSITIVE

Feature 2: Inattention

• Perform auditory test: "I'm going to read you a series of letters. Squeeze my hand every time I say the letter A."
• Read: S-A-V-E-A-H-A-A-R-T (10 letters, 3 target A's)
• Count errors (likely greater than 2 errors given agitation, disorientation)
• Feature 2: POSITIVE

Feature 3: Altered level of consciousness

• Current RASS score: +2 (agitated) - this is NOT zero
• Feature 3: POSITIVE

Feature 4: Disorganized thinking

• Ask 4 yes/no questions:
  1. "Will a stone float on water?" (No)
  2. "Are there fish in the sea?" (Yes)
  3. "Does one pound weigh more than two pounds?" (No)
  4. "Can you use a hammer to pound a nail?" (Yes)
• Command: "Hold up this many fingers" (hold up 2), then "Now do the same thing with the other hand"
• Count errors (likely greater than 1 given confusion)
• Feature 4: POSITIVE

CAM-ICU Interpretation:

• Features 1 AND 2 AND (3 OR 4) present
• CAM-ICU POSITIVE → Delirium confirmed
• Subtype: Hyperactive delirium (agitation, attempting to leave bed)

Identify and Treat Underlying Causes:

Medication Review:

• Recent medications: Benzodiazepines? Opioids? Anticholinergics?
• Anticholinergic burden score
• Consider deprescribing/reducing delirogenic medications

Metabolic/Systemic:

• Hypoxia: Check SpO2, ABG (post-extubation respiratory failure?)
• Electrolytes: Hypo/hypernatremia, hypercalcemia
• Hypoglycemia or hyperglycemia
• Uremia (renal function)
• Infection: Sepsis recurrence, new HAP/VAP, UTI (cultures, CRP, WCC)

Neurological:

• Intracranial pathology: Stroke, hemorrhage (unlikely if acute onset post-extubation, but consider if atypical)

Pain:

• Undertreated pain (assess with BPS or numeric scale if able)

Non-Pharmacological Management (FIRST-LINE):

Immediate:

• Safety: Bed low, sitter or family member present, avoid physical restraints
• Reorientation: Clock, calendar, reassure patient, explain where she is
• Family engagement: Call family, encourage visiting
• Sensory aids: Glasses, hearing aids if normally used
• Environment: Quiet, well-lit during day, reduce stimulation

Ongoing:

• Implement ABCDEF bundle elements
• Pain control
• Early mobility once delirium improves
• Sleep hygiene (dim lights at night, earplugs if tolerated)

Pharmacological Management (if needed):

• Only if non-pharmacological measures fail AND agitation poses safety risk
• Haloperidol 0.5 mg IV (lower dose in elderly)
• Monitor for response after 30-60 minutes, can repeat
• Check baseline ECG (QTc prolongation risk)
• Avoid benzodiazepines (worsens delirium)

Examiner Follow-Up Questions:

Q: The nurse wants to apply wrist restraints to prevent line removal. How would you respond? A: Physical restraints are a MODIFIABLE risk factor for delirium and should be avoided except as a last resort for immediate safety. Alternatives:

• Sitter or family member at bedside
• Move patient to room near nurses' station (closer observation)
• Consider covering lines (tubular bandage) rather than restraining wrists
• If restraints absolutely necessary (no other option): Use least restrictive method, frequent reassessment, document indication, plan for removal

Q: What is the evidence for haloperidol in delirium treatment? A:

• Multiple large RCTs show NO benefit for delirium duration or mortality
• MIND-USA trial: Haloperidol vs placebo - no difference in delirium-free days
• HOPE-ICU trial: Haloperidol vs placebo - no mortality benefit
• AID-ICU trial: No improvement in delirium days or 90-day mortality
• SCCM guidelines: DO NOT routinely use; consider only for safety/agitation
• Use haloperidol for symptom control (agitation), NOT to treat delirium itself

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Viva 2: ABCDEF Bundle Implementation

Scenario: You are the ICU consultant leading a quality improvement project to reduce delirium in your unit. Describe how you would implement the ABCDEF bundle and the evidence supporting it.

Expected Discussion Points:

Bundle Overview:

• Evidence-based, multicomponent intervention
• Part of ICU Liberation Campaign (SCCM)
• Requires multidisciplinary coordination (doctors, nurses, physiotherapists, pharmacists, families)

A: Assess, Prevent, and Manage Pain

Implementation:

• Standardize pain assessment tools:
  • BPS (Behavioral Pain Scale) or CPOT for intubated/non-communicative
  • Numeric Rating Scale for communicative patients
• Document pain scores with vital signs (every 4 hours minimum)
• Multimodal analgesia protocol:
  • Paracetamol, NSAIDs, regional blocks (reduce opioid)
  • Opioids for breakthrough pain

Rationale:

• Untreated pain is delirium precipitant
• Over-sedation to mask pain worsens delirium
• Treat pain BEFORE sedating

B: Both Spontaneous Awakening Trial (SAT) and Spontaneous Breathing Trial (SBT)

Implementation:

• SAT (Sedation Interruption):
  • Daily interruption of sedation infusions
  • Screen for safety contraindications (seizures, agitation, ICP concerns, active withdrawal, myocardial ischemia)
  • "If passes screen: Stop sedation until patient wakes (RASS ≥ -1) or becomes uncomfortable"
  • Restart at 50% previous rate
• SBT:
  • "If passes SAT and SBT safety screen: Perform SBT (T-piece or PSV 5-8 cmH2O)"
  • Assess for extubation readiness

Coordination:

• Nurse performs SAT first, then notifies respiratory therapist for SBT if appropriate
• Reduces delirium, ventilator days, mortality

Evidence:

• Girard et al. Lancet 2008: SAT + SBT coordination reduced mortality, ventilator days

C: Choice of Analgesia and Sedation

Implementation:

• Avoid benzodiazepines except for specific indications:
  • Alcohol/benzodiazepine withdrawal
  • Seizures
  • Specific anesthesia situations
• Preferred sedatives:
  • "Propofol: Short-acting, but no delirium benefit"
  • "Dexmedetomidine: α2-agonist, reduces delirium vs benzodiazepines"
• Target light sedation: RASS 0 to -1 (unless contraindicated: e.g., paralysis, ICP management)
• No sedation for many extubated patients

Evidence:

• MENDS trial: Dexmedetomidine vs lorazepam - more delirium-free days
• SEDCOM trial: Dexmedetomidine vs midazolam - lower delirium
• Benzodiazepines = strongest modifiable delirium risk factor

D: Delirium - Assess, Prevent, and Manage

Implementation:

• Screening: CAM-ICU or ICDSC every shift (every 8-12 hours)
• Train ALL nurses in delirium screening (CAM-ICU workshops, competency assessment)
• Document delirium status in electronic medical record
• Non-pharmacological interventions (see below)
• Identify and treat precipitants (infection, metabolic, medications)

E: Early Mobility and Exercise

Implementation:

• Assess mobility level daily
• Mobilization protocol:
  • "Level 1: Passive range of motion"
  • "Level 2: Active range of motion"
  • "Level 3: Sitting at edge of bed"
  • "Level 4: Transfer to chair"
  • "Level 5: Ambulation with assistance"
• Physiotherapy consult within 24 hours of ICU admission
• Safety screen: Hemodynamic stability, no active bleeding, FiO2 below 0.6, PEEP below 10

Evidence:

• Schweickert et al. Lancet 2009: Early mobility reduced delirium, improved functional outcomes
• Morris et al. 2016: Early mobility feasible and safe in mechanically ventilated patients

F: Family Engagement and Empowerment

Implementation:

• Unrestricted visiting hours (24/7 access) when feasible
• Include family in multidisciplinary rounds
• Family education handout: "What is delirium? How can you help?"
• Encourage family to bring familiar objects (photos, music)
• Family participation in reorientation

Evidence:

• Restricted visiting hours associated with higher delirium
• Family presence reduces patient anxiety, improves orientation

Evidence for Bundle as a Whole:

Pun et al. 2019 (ICU Liberation Collaborative) - PMID 30339549:

• greater than 15,000 ICU patients across multiple hospitals
• Dose-response: Higher bundle compliance → better outcomes
• 68% reduction in likelihood of death with high compliance
• 25-50% reduction in delirium duration
• Shorter mechanical ventilation, more home discharges

Barnes-Daly et al. 2017 - PMID 28359489:

• Even partial bundle compliance improved outcomes
• Reduced hospital mortality, more delirium/coma-free days

Implementation Barriers and Solutions:

Barriers:

• Culture change required (traditional deep sedation culture)
• Perceived time constraints (screening adds workload)
• Interdisciplinary coordination (SAT + SBT requires nurse + RT communication)
• Staff education and training

Solutions:

• Leadership buy-in (ICU director, nurse manager)
• Multidisciplinary education sessions (grand rounds, in-services)
• Electronic medical record integration (automatic prompts for screening)
• Audit and feedback (monthly bundle compliance reports)
• Champion model (delirium champions on each shift)
• Start with one element, gradually add others

Examiner Follow-Up Questions:

Q: Why is the bundle superior to single interventions? A:

• Delirium is multifactorial (pain, sedation, immobility, sensory deprivation, sleep disruption)
• Addressing only one factor (e.g., sedation choice) insufficient
• Synergistic effect: SAT allows early mobility, early mobility reduces delirium, reduced delirium shortens ventilation
• Bundle addresses the entire ICU environment and culture

Q: What would you do if your nursing staff resists SAT implementation? A:

• Understand concerns (fear of patient discomfort, self-extubation, workload)
• Present evidence (mortality benefit, ventilator days)
• Start with low-risk patients (post-op elective, stable medical)
• Provide robust safety screening criteria (clear contraindications)
• Ensure physician availability for backup (restart sedation if needed)
• Celebrate successes (early extubations, reduced delirium)
• Iterative process: Pilot phase, feedback, adjust protocol

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Viva 3: Dexmedetomidine vs Benzodiazepines

Scenario: A 55-year-old man with ARDS (Day 3 of mechanical ventilation) is requiring increasing doses of midazolam and fentanyl. He is agitated (RASS +2) whenever sedation is lightened. His current sedation is midazolam 10 mg/h and fentanyl 150 mcg/h. Discuss your sedation management strategy.

Expected Discussion Points:

Assessment:

• ARDS Day 3, mechanically ventilated
• Agitation (RASS +2) - target should be RASS 0 to -1
• High-dose benzodiazepine (midazolam 10 mg/h)
• Opioid infusion (fentanyl 150 mcg/h)

Problems with Current Sedation:

• Benzodiazepine: Strongest modifiable risk factor for delirium
• Deep sedation culture: Increasing doses rather than addressing cause of agitation
• RASS +2: Inappropriate sedation depth
• High delirium risk: Benzodiazepine, mechanical ventilation, agitation

Initial Management:

Identify Cause of Agitation (before escalating sedation):

• Pain: Assess with BPS/CPOT (may need more analgesia, NOT sedation)
• Ventilator dyssynchrony: Check ventilator settings, flow rate, trigger sensitivity, mode
• Respiratory distress: Hypoxia, hypercapnia, auto-PEEP (check ABG, adjust vent)
• Delirium: Already delirious vs sedation withdrawal
• Metabolic: Hypoglycemia, electrolyte disturbance
• Urinary retention, constipation (discomfort)

Sedation Strategy - Transition to Dexmedetomidine:

Rationale for Dexmedetomidine:

• α2-adrenergic agonist (NOT GABA-mediated like benzodiazepines)
• Sedation via locus coeruleus → preserves more natural sleep architecture
• Reduces delirium incidence vs benzodiazepines
• Minimal respiratory depression (cooperative sedation)
• Easier to perform SAT, early mobility

Evidence:

• MENDS trial (Riker et al. JAMA 2009 - PMID 19336710):
  • Dexmedetomidine vs lorazepam in mechanically ventilated patients
  • "Dexmedetomidine: More delirium-free days (7.0 vs 3.0 days)"
  • More time at target RASS
  • Trend toward lower mortality (not statistically significant)
• SEDCOM trial (Riker et al. JAMA 2009 - PMID 19336711):
  • Dexmedetomidine vs midazolam
  • Lower delirium prevalence (54% vs 76%)
  • Shorter time to extubation (3.7 vs 5.6 days)

Transition Protocol:

Step 1: Start Dexmedetomidine

• Loading dose: NOT recommended in this agitated patient (may worsen hypotension)
• Infusion: Start 0.4 mcg/kg/h (no bolus)
• Titrate up to 0.7-1.5 mcg/kg/h based on RASS goal (RASS 0 to -1)

Step 2: Wean Midazolam

• Do NOT stop abruptly (risk of benzodiazepine withdrawal, seizure)
• Reduce by 25-50% every 2-4 hours as dexmedetomidine titrated up
• Monitor for withdrawal (agitation, tachycardia, hypertension, seizures)

Step 3: Optimize Analgesia

• Continue fentanyl infusion (pain control)
• Consider multimodal: Paracetamol, ketamine (sub-anesthetic dose 0.05-0.1 mg/kg/h)
• Opioid-sparing strategies to facilitate weaning

Step 4: Daily Sedation Interruption (SAT)

• Once on dexmedetomidine alone, implement daily SAT
• Assess for SBT readiness
• Coordinate with respiratory therapist

Monitoring:

• Cardiovascular: Continuous ECG, BP monitoring
  • "Bradycardia (20-25% incidence): Usually not clinically significant, may need rate reduction"
  • "Hypotension (25-30%): Fluid bolus, reduce rate, may need vasopressor"
• RASS score every 2-4 hours: Target RASS 0 to -1
• CAM-ICU every 8-12 hours: Screen for delirium
• Pain score (BPS/CPOT) every 4 hours

Adverse Effects of Dexmedetomidine:

• Bradycardia: HR below 40 bpm (reduce rate or stop temporarily)
• Hypotension: SBP below 80 mmHg (fluid, vasopressor, reduce rate)
• Hypertension (transient): Rare, usually on loading bolus (not using loading)
• Cost: More expensive than propofol/benzodiazepines (but offset by reduced delirium, shorter ventilation)

Contraindications/Cautions:

• Advanced heart block (2nd/3rd degree AV block) without pacemaker
• Severe bradycardia (HR below 50 bpm) or hypotension (SBP below 90 mmHg)
• Acute cerebrovascular events (may reduce cerebral perfusion)

Alternative if Dexmedetomidine Not Tolerated:

• Propofol: Does NOT reduce delirium vs benzodiazepines, but shorter wake-up time
• Still AVOID benzodiazepine if possible
• Continue analgesia-first approach

Examiner Follow-Up Questions:

Q: The patient develops bradycardia (HR 45 bpm) on dexmedetomidine 0.8 mcg/kg/h. How would you manage this? A:

• Assess clinical significance:
  • Is patient symptomatic? (Hypotension, dizziness, reduced perfusion)
  • Check BP (bradycardia alone may not be harmful if BP maintained)
• If asymptomatic and BP stable: Observe, may not require intervention
• If symptomatic or BP below 90 mmHg:
  • Reduce dexmedetomidine rate (e.g., to 0.4-0.5 mcg/kg/h)
  • Fluid bolus 250-500 mL if volume-responsive
  • Consider glycopyrrolate 0.2 mg IV (anticholinergic) if persistent
  • "If severe/refractory: Stop dexmedetomidine, transition to propofol"
• Bradycardia usually resolves with rate reduction

Q: Compare dexmedetomidine and propofol for sedation in ARDS. A:

Choice in ARDS:

• Dexmedetomidine preferred if goal is delirium reduction, early mobility, easier SAT/SBT
• Propofol if cost is concern, or if bradycardia/hypotension contraindicate dexmedetomidine
• Both superior to benzodiazepines

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Viva 4: Long-Term Cognitive Outcomes and PICS

Scenario: A family member of a 60-year-old ICU survivor (Day 14 ARDS, Day 10 delirium) asks: "Will his confusion get better when he leaves the ICU? Will he be able to go back to work?" Discuss your response and the evidence for long-term cognitive outcomes after ICU delirium.

Expected Discussion Points:

Initial Response to Family (Empathetic, Honest):

• Acknowledge concern and family distress
• Explain that delirium often improves after ICU discharge as acute illness resolves and environment normalizes
• However, some patients experience long-lasting cognitive changes (Post-Intensive Care Syndrome - PICS)
• Delirium duration (10 days) is a significant risk factor for longer-term cognitive impairment
• Prognosis is individualized; some recover fully, others have persistent deficits

Post-Intensive Care Syndrome (PICS):

Definition:

• New or worsening impairments in physical, cognitive, and mental health arising after critical illness
• Affects 30-50% of ICU survivors

Three Domains:

1. Physical: ICU-acquired weakness, reduced exercise tolerance, fatigue
2. Cognitive: Executive dysfunction, memory problems, reduced processing speed
3. Psychological: PTSD, depression, anxiety

Cognitive Impairment - BRAIN-ICU Study:

Study Design (Pandharipande et al. NEJM 2013 - PMID 24088092):

• Prospective multicenter cohort
• ICU survivors assessed at 3 and 12 months post-discharge
• Comprehensive neuropsychological testing

Key Findings:

• At 3 months:
  • 40% had global cognitive scores similar to moderate traumatic brain injury
  • 26% had scores similar to mild Alzheimer's disease
• At 12 months:
  • Cognitive impairment persisted in 30-50% of survivors
• Delirium duration was strongest independent predictor:
  • "Dose-response relationship: Longer delirium → worse cognition"
  • Each additional day of delirium associated with decreased cognitive performance
• Age not protective:
  • Young, previously healthy patients equally affected as elderly

Cognitive Domains Affected:

• Executive function: Planning, organizing, problem-solving (difficulty multitasking, managing finances)
• Memory: Short-term recall, working memory (forget appointments, medications)
• Attention and processing speed: Reduced concentration, slower thinking
• Visuospatial abilities: Difficulty navigating, spatial relationships

Functional Impact (Return to Work):

• Many survivors unable to return to previous employment
• Reduced work hours or less demanding roles
• Difficulty with Instrumental Activities of Daily Living (IADLs): Managing finances, medications, shopping
• Lower quality of life scores
• Higher rates of institutionalization (nursing home, assisted living)

Pathophysiology (Why Does Delirium Cause Long-Term Damage?):

Neuroinflammation:

• Systemic inflammation (sepsis, ARDS) crosses blood-brain barrier
• Cytokine-mediated brain injury
• Persistent microglial activation even after ICU

Neuronal Damage:

• Oxidative stress, reactive oxygen species
• Neuronal apoptosis (cell death) in hippocampus, prefrontal cortex
• Brain volume loss (atrophy) on MRI
• Hippocampal atrophy correlates with memory impairment

Vascular Injury:

• Microvascular thrombosis, ischemia
• Blood-brain barrier dysfunction

Risk Factors for Worse Cognitive Outcomes:

• Longer delirium duration (10 days is significant)
• Pre-existing cognitive frailty (even if undiagnosed)
• Prolonged mechanical ventilation
• Older age
• Lower educational level

What Can We Do? (Prevention and Mitigation):

During ICU Stay:

• ABCDEF bundle: High compliance reduces delirium duration
• Avoid benzodiazepines
• Early mobility, family engagement
• Light sedation targets
• Every day of delirium prevented → improved long-term cognition

Post-ICU:

• ICU follow-up clinic (if available): Screen for PICS at 3-6 months
• Cognitive rehabilitation (occupational therapy, neuropsychology)
• Physical rehabilitation (physiotherapy for weakness)
• Psychological support (PTSD, depression screening and treatment)
• Family education and support (PICS-Family for caregivers)

Prognosis for This Patient:

Positive Factors:

• Age 60 (younger than many ICU patients)
• If no pre-existing dementia

Negative Factors:

• 10 days of delirium (prolonged duration)
• ARDS (severity of illness)

Realistic Expectations:

• Delirium will likely improve after ICU discharge (as sepsis resolves, sedation stopped, environment normalizes)
• However, risk of persistent cognitive deficits at 3-6 months is SIGNIFICANT (40-50% chance)
• May experience memory problems, difficulty concentrating, slower thinking
• Return to work possible but may need accommodations (reduced hours, less cognitively demanding role)
• Recovery trajectory highly individual (some improve 6-12 months, others plateau)

Follow-Up Plan:

• Arrange ICU follow-up clinic appointment (3 months post-discharge)
• Screen for cognitive impairment (Montreal Cognitive Assessment - MoCA)
• Refer to neuropsychology if deficits identified
• Occupational therapy assessment for ADL/IADL support
• Provide PICS education handout for patient and family

Examiner Follow-Up Questions:

Q: The family asks if there are any medications that can prevent long-term cognitive decline. What would you say? A:

• Unfortunately, NO medications have been proven to prevent or treat ICU-related cognitive impairment
• Acetylcholinesterase inhibitors (rivastigmine, donepezil):
  • Tested in ICU delirium trials
  • "Van Eijk et al. Lancet 2010: Rivastigmine INCREASED mortality and longer delirium (trial stopped early)"
  • NOT recommended
• Antipsychotics (haloperidol, quetiapine):
  • Do NOT reduce delirium duration or improve long-term outcomes
  • Multiple RCTs show no benefit
• Best approach: PREVENTION
  • ABCDEF bundle during ICU stay
  • Avoid benzodiazepines, promote early mobility
  • Reduce delirium duration → improves long-term cognition

Q: How would you screen for PICS in an ICU follow-up clinic? A:

Physical Domain:

• Handgrip strength: Dynamometer (sex and age-adjusted)
• 6-minute walk test: Distance walked in 6 minutes
• Assess for ICU-acquired weakness, exercise tolerance
• Referral to physiotherapy if deficits

Cognitive Domain:

• Montreal Cognitive Assessment (MoCA): 30-point screening tool
  • below 26/30 suggests cognitive impairment
• Domains: Attention, memory, executive function, language, visuospatial
• If positive: Refer to neuropsychology for comprehensive testing

Psychological Domain:

• HADS (Hospital Anxiety and Depression Scale): Screening for anxiety/depression
• PTSS-14 (Post-Traumatic Stress Syndrome 14): Screen for PTSD
• If positive: Refer to psychiatry/psychology

Functional Assessment:

• Activities of Daily Living (ADLs): Bathing, dressing, toileting
• Instrumental ADLs (IADLs): Cooking, finances, medications, shopping
• Return to work status, quality of life (SF-36 or EQ-5D)

Interventions:

• Multidisciplinary approach (physiotherapy, occupational therapy, neuropsychology, psychiatry)
• Cognitive rehabilitation for executive dysfunction
• Family support (PICS-Family education)

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OSCE Stations

OSCE 1: CAM-ICU Delirium Screening

Station Setup:

• Candidate Role: ICU registrar
• Actor Role: ICU patient (post-operative Day 2, extubated)
• Task: Perform CAM-ICU assessment and communicate findings to examiner

Scenario: You are an ICU registrar. The nurse has asked you to assess Mrs. Brown, a 70-year-old woman who is Day 2 post-total hip replacement. She was extubated yesterday. The nurse reports she is "a bit confused this morning." Please assess Mrs. Brown for delirium using the CAM-ICU tool.

Actor Instructions:

• You are drowsy but arousable to voice (RASS -1)
• You answer questions slowly but appropriately for Feature 1
• Inattention test: You squeeze hand randomly, making 3-4 errors (positive)
• Yes/No questions: You get 2 out of 4 correct (positive for disorganized thinking)
• Command: You struggle to follow the two-step command (positive)
• You ask "Where am I?" occasionally

Marking Criteria (Total: 20 marks)

Introduction and Consent (2 marks)

• Introduces self and role (1 mark)
• Explains purpose of assessment in simple terms (1 mark)

RASS Assessment (2 marks)

• Assesses level of consciousness first (1 mark)
• Correctly identifies RASS score (-1: drowsy) and states patient is arousable for CAM-ICU (1 mark)

Feature 1: Acute Onset or Fluctuating Course (3 marks)

• Asks nurse: "Is this an acute change from baseline mental status?" (1 mark)
• Asks: "Has behavior fluctuated over the past 24 hours?" (1 mark)
• Correctly identifies Feature 1 as POSITIVE (1 mark)

Feature 2: Inattention (4 marks)

• Explains test clearly: "Squeeze my hand when I say the letter A" (1 mark)
• Correctly performs auditory test (SAVEAHAART or equivalent) (1 mark)
• Counts errors accurately (greater than 2 errors) (1 mark)
• Correctly identifies Feature 2 as POSITIVE (1 mark)

Feature 3: Altered Level of Consciousness (2 marks)

• States current RASS score is -1 (not zero) (1 mark)
• Correctly identifies Feature 3 as POSITIVE (1 mark)

Feature 4: Disorganized Thinking (4 marks)

• Asks 4 yes/no questions correctly:
  • "Will a stone float on water?" (No)
  • "Are there fish in the sea?" (Yes)
  • "Does one pound weigh more than two?" (No)
  • "Can you use a hammer to pound a nail?" (Yes) (2 marks)
• Performs command correctly: "Hold up this many fingers" then "Do the same with other hand" (1 mark)
• Correctly identifies Feature 4 as POSITIVE (greater than 1 error) (1 mark)

CAM-ICU Interpretation (2 marks)

• States CAM-ICU is POSITIVE (Features 1 AND 2 AND [3 OR 4]) (1 mark)
• Correctly concludes patient has delirium (1 mark)

Communication and Professionalism (1 mark)

• Communicates findings clearly to examiner (0.5 marks)
• Professional, empathetic manner with patient (0.5 marks)

Total: /20 marks

Pass Mark: 14/20 (70%)

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OSCE 2: Explaining PICS to Family

Station Setup:

• Candidate Role: ICU consultant
• Actor Role: Wife of ICU patient
• Task: Explain Post-Intensive Care Syndrome (PICS) and long-term cognitive risks

Scenario: You are an ICU consultant. Mr. Smith (65 years old) is Day 12 in ICU following severe community-acquired pneumonia and ARDS. He has had 8 days of delirium. He is improving but still confused. His wife asks to speak with you. She wants to know: "Will his confusion get better? Will he be back to normal when he leaves hospital?" Please explain PICS and the potential for long-term cognitive impairment.

Actor Instructions:

• You are anxious and worried about your husband's recovery
• You have noticed he doesn't recognize you sometimes
• You are concerned about his ability to return to work (he is an accountant)
• You become tearful when told about possible long-term effects
• You appreciate honesty but need reassurance that something can be done

Marking Criteria (Total: 20 marks)

Introduction and Rapport (2 marks)

• Introduces self and role (0.5 marks)
• Asks what she understands so far (0.5 marks)
• Sits down, appropriate body language (0.5 marks)
• Acknowledges her concerns empathetically (0.5 marks)

Explains Delirium (2 marks)

• Explains delirium is common in ICU (30-50% of patients) (1 mark)
• States that delirium often improves as infection resolves and patient leaves ICU (1 mark)

Introduces PICS Concept (3 marks)

• Explains PICS = Post-Intensive Care Syndrome (1 mark)
• States 30-50% of ICU survivors affected (1 mark)
• Describes 3 domains: Physical (weakness), Cognitive (thinking/memory), Psychological (anxiety/depression) (1 mark)

Explains Cognitive Impairment Risk (5 marks)

• States that delirium duration (8 days) is a risk factor for long-term cognitive problems (1 mark)
• Explains 30-50% of ICU survivors have cognitive impairment at 3-12 months (1 mark)
• Describes affected domains: Memory, concentration, problem-solving, processing speed (1 mark)
• Uses appropriate analogy: "Similar to mild traumatic brain injury or early Alzheimer's" (1 mark)
• States this can affect return to work, managing finances, daily tasks (1 mark)

Provides Realistic Hope (3 marks)

• States that some patients improve over 6-12 months (1 mark)
• Explains recovery is individual and hard to predict (1 mark)
• Emphasizes that delirium is improving, which is positive (1 mark)

Outlines Support and Follow-Up (3 marks)

• Explains ICU follow-up clinic will screen for PICS (1 mark)
• Mentions cognitive rehabilitation, physiotherapy, psychological support available (1 mark)
• Offers to involve family in recovery planning (1 mark)

Communication Skills (2 marks)

• Avoids jargon, uses clear language (0.5 marks)
• Checks understanding ("Does that make sense?") (0.5 marks)
• Responds to distress appropriately (allows silence, offers tissue) (0.5 marks)
• Summarizes key points (0.5 marks)

Total: /20 marks

Pass Mark: 14/20 (70%)

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OSCE 3: Delirium Management Discussion

Station Setup:

• Candidate Role: ICU registrar presenting to consultant
• Examiner Role: ICU consultant
• Task: Discuss management plan for delirious patient

Scenario: You are the ICU registrar on night shift. You are called to see Mr. Jones, a 58-year-old man, Day 4 post-emergency laparotomy for perforated diverticulitis. He is extubated, receiving 2L/min oxygen via nasal prongs. He is pulling at his IV lines, trying to get out of bed, and shouting "I need to leave!" CAM-ICU is positive (hyperactive delirium). Present your management plan to the ICU consultant (examiner).

Marking Criteria (Total: 20 marks)

Initial Assessment and Safety (3 marks)

• Ensures immediate safety (bed low, sitter, avoid restraints unless essential) (1 mark)
• Confirms delirium with CAM-ICU (already done) and identifies subtype (hyperactive) (1 mark)
• Assesses ABCDE (airway, breathing, circulation stable) (1 mark)

Identify and Treat Underlying Causes (5 marks)

• Medication review: Check for benzodiazepines, anticholinergics, high-dose opioids (1 mark)
• Metabolic: Electrolytes, glucose, renal function, blood gas (hypoxia, hypercapnia) (1 mark)
• Infection: Sepsis (surgical site, pneumonia, UTI) - cultures, WCC, CRP (1 mark)
• Pain: Assess pain score, optimize analgesia (1 mark)
• Other: Urinary retention, constipation, alcohol withdrawal (1 mark)

Non-Pharmacological Interventions (FIRST-LINE) (5 marks)

• Reorientation: Clock, calendar, reassure patient, explain where he is (1 mark)
• Family engagement: Contact family, encourage visiting (1 mark)
• Environment: Quiet, well-lit during day, reduce stimulation (1 mark)
• Sensory aids: Glasses, hearing aids if used (1 mark)
• Avoid restraints: Use sitter or family instead (1 mark)

Pharmacological Management (if needed) (4 marks)

• States pharmacological intervention ONLY if non-pharmacological fails and safety risk exists (1 mark)
• Haloperidol 0.5-1 mg IV (first-line antipsychotic for agitation) (1 mark)
• Acknowledges evidence: Antipsychotics do NOT reduce delirium duration/mortality, only control symptoms (1 mark)
• States need to monitor ECG (QTc prolongation) and avoid benzodiazepines (1 mark)

ABCDEF Bundle Application (2 marks)

• Mentions implementing bundle elements: Pain control, avoid benzodiazepines, early mobility, family engagement (1 mark)
• Plans to screen for delirium regularly (CAM-ICU every 8-12 hours) (1 mark)

Communication and Professionalism (1 mark)

• Clear, structured presentation to consultant (0.5 marks)
• Demonstrates understanding of evidence-based approach (0.5 marks)

Total: /20 marks

Pass Mark: 14/20 (70%)

---

References

1. 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

2. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306. doi:10.1097/CCM.0b013e3182783b72 [PMID: 23269131]

3. 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

4. Pun BT, Balas MC, Barnes-Daly MA, et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3-14. doi:10.1097/CCM.0000000000003482 [PMID: 30339549]

5. Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6,064 patients. Crit Care Med. 2017;45(2):171-178. doi:10.1097/CCM.0000000000002149 [PMID: 28359489]

6. 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

7. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316. doi:10.1056/NEJMoa1301372 [PMID: 24088092]

8. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299

9. Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523. doi:10.1016/S2213-2600(13)70166-8 [PMID: 23842231]

10. Girard TD, Exline MC, Carson SS, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379(26):2506-2516. doi:10.1056/NEJMoa1808217 [PMID: 30346242]

11. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489-499. doi:10.1001/jama.2009.56 [PMID: 19188334]

12. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653. doi:10.1001/jama.298.22.2644

13. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

14. Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med. 2007;33(6):1007-1013. doi:10.1007/s00134-007-0618-y

15. Salluh JI, Wang H, Schneider EB, et al. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ. 2015;350:h2538. doi:10.1136/bmj.h2538

16. 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

17. Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999;54(6):B239-B246. doi:10.1093/gerona/54.6.b239

18. Simone MJ, Tan ZS. The role of inflammation in the pathogenesis of delirium and dementia in older adults: a review. CNS Neurosci Ther. 2011;17(5):506-513. doi:10.1111/j.1755-5949.2010.00173.x

19. 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

20. Kamdar BB, Needham DM, Collop NA. Sleep deprivation in critical illness: its role in physical and psychological recovery. J Intensive Care Med. 2012;27(2):97-111. doi:10.1177/0885066610394322

21. Van Rompaey B, Elseviers MM, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009;13(3):R77. doi:10.1186/cc7892

22. Gusmao-Flores D, Salluh JI, Chalhub RÁ, Quarantini LC. The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit Care. 2012;16(4):R115. doi:10.1186/cc11407

23. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001;27(5):859-864. doi:10.1007/s001340100909

24. Neto AS, Nassar AP Jr, Cardoso SO, et al. Delirium screening in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2012;40(6):1946-1951. doi:10.1097/CCM.0b013e31824e16c9

25. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338-1344. doi:10.1164/rccm.2107138

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

27. van den Boogaard M, Pickkers P, Slooter AJ, et al. Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ. 2012;344:e420. doi:10.1136/bmj.e420

28. Wassenaar A, van den Boogaard M, van Achterberg T, et al. Multinational development and validation of an early prediction model for delirium in ICU patients. Intensive Care Med. 2015;41(6):1048-1056. doi:10.1007/s00134-015-3777-2

29. Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF bundle in critical care. Crit Care Clin. 2017;33(2):225-243. doi:10.1016/j.ccc.2016.12.005 [PMID: 27984310]

30. Payen JF, Chanques G, Mantz J, et al. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007;106(4):687-695. doi:10.1097/01.anes.0000264747.09017.da

31. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134. doi:10.1016/S0140-6736(08)60105-1

32. Fraser GL, Devlin JW, Worby CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013;41(9 Suppl 1):S30-S38. doi:10.1097/CCM.0b013e3182a16898

33. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009;373(9678):1874-1882. doi:10.1016/S0140-6736(09)60658-9

34. Morris PE, Berry MJ, Files DC, et al. Standardized rehabilitation and hospital length of stay among patients with acute respiratory failure: a randomized clinical trial. JAMA. 2016;315(24):2694-2702. doi:10.1001/jama.2016.7201

35. Rosa RG, Falavigna M, da Silva DB, et al. Effect of flexible family visitation on delirium among patients in the intensive care unit: the ICU visits randomized clinical trial. JAMA. 2019;322(3):216-228. doi:10.1001/jama.2019.8766

36. Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016;3:CD005563. doi:10.1002/14651858.CD005563.pub3

37. Van Rompaey B, Elseviers MM, Van Drom W, Fromont V, Jorens PG. The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit Care. 2012;16(3):R73. doi:10.1186/cc11330 [PMID: 22559080]

38. Litton E, Carnegie V, Elliott R, Webb SA. The efficacy of earplugs as a sleep hygiene strategy for reducing delirium in the ICU: a systematic review and meta-analysis. Crit Care Med. 2016;44(5):992-999. doi:10.1097/CCM.0000000000001557

39. Andersen-Ranberg NC, Poulsen LM, Perner A, Wetterslev J, Estrup S, Hästbacka J. Haloperidol for the treatment of delirium in ICU patients. N Engl J Med. 2022;387(26):2425-2435. doi:10.1056/NEJMoa2211868

40. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010;38(2):419-427. doi:10.1097/CCM.0b013e3181b9e302

41. Reade MC, Eastwood GM, Bellomo R, et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460-1468. doi:10.1001/jama.2016.2707

42. van Eijk MM, Roes KC, Honing ML, et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial. Lancet. 2010;376(9755):1829-1837. doi:10.1016/S0140-6736(10)61855-7

43. Garland A, Olafson K, Ramsey CD, Yogendran M, Fransoo R. Epidemiology of critically ill patients in intensive care units: a population-based observational study. Crit Care. 2013;17(5):R212. doi:10.1186/cc13026

44. Lewis SR, Schofield-Robinson OJ, Alderson P, Smith AF. Melatonin for the promotion of sleep in adults in the intensive care unit. Cochrane Database Syst Rev. 2018;5:CD012455. doi:10.1002/14651858.CD012455.pub2

45. DeCarolis DD, Rice KL, Ho L, Willenbring ML, Cassaro S. Symptom-driven lorazepam protocol for treatment of severe alcohol withdrawal delirium in the intensive care unit. Pharmacotherapy. 2007;27(4):510-518. doi:10.1592/phco.27.4.510

46. Glumac S, Kardum G, Sodic L, et al. Effects of dexamethasone on early cognitive decline after cardiac surgery: a randomised controlled trial. Eur J Anaesthesiol. 2017;34(11):776-784. doi:10.1097/EJA.0000000000000647

47. Needham DM, Davidson J, Cohen H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2012;40(2):502-509. doi:10.1097/CCM.0b013e318232da75

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 [PMID: 20473145]

49. Wolters AE, van Dijk D, Pasma W, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care. 2014;18(3):R125. doi:10.1186/cc13929