Post-Intensive Care Syndrome (PICS)

Answer Card

Post-Intensive Care Syndrome (PICS) encompasses new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond acute care hospitalization. Coined by the Society of Critical Care Medicine in 2010, PICS affects approximately 50% of ICU survivors and represents a paradigm shift from survival-focused to recovery-focused critical care.

Three Core Domains:

• Physical: ICU-acquired weakness (ICUAW), fatigue, chronic pain, functional decline, frailty (25-50% at discharge, 20-30% at 12 months)
• Cognitive: Memory deficits, executive dysfunction, attention impairment, processing speed reduction (25-50% at 12 months, equivalent to mild TBI or early Alzheimer's)
• Mental Health: PTSD (10-27%), depression (25-35%), anxiety (30-40%), persisting for years

PICS-F (Family): Family members experience psychological morbidity including anxiety (70%), depression (35%), PTSD (30%), caregiver burden, and complicated grief, often exceeding patient burden.

Prevention (ABCDEF Bundle):

• Assess, Prevent, Manage Pain
• Both Spontaneous Awakening and Breathing Trials
• Choice of Analgesia and Sedation (avoid benzodiazepines)
• Delirium: Assess, Prevent, Manage
• Early Mobility and Exercise
• Family Engagement and Empowerment

BRAIN-ICU Study: Longer duration of delirium independently predicts worse cognitive impairment at 3 and 12 months (PMID: 24088092). Each additional day of delirium associated with 10% increased odds of cognitive impairment.

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CICM Exam Focus

SAQ Stems

• "Discuss the domains of Post-Intensive Care Syndrome (PICS) and evidence-based prevention strategies"
• "A 55-year-old man 3 months post-septic shock reports persistent fatigue, memory problems, and flashbacks. Outline your assessment and management"
• "Describe the ABCDEF bundle and its role in preventing PICS"
• "Outline the evidence for ICU follow-up clinics in improving long-term outcomes"

Hot Case Presentations

• Patient with prolonged ICU stay referred for post-ICU assessment
• Delayed discharge due to ongoing weakness and confusion
• Family conference regarding prognosis for long-term recovery
• Discussion of rehabilitation goals with multidisciplinary team

Viva Topics

• BRAIN-ICU study findings and clinical implications
• Pathophysiology of ICU-acquired cognitive impairment
• Evidence for early mobilisation
• PICS-F and family-centred care
• Role of ICU diaries
• Critical appraisal of ICU follow-up clinic evidence
• Australian/NZ rehabilitation pathways

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Key Points

1. Definition: PICS encompasses new or worsening impairments in physical, cognitive, or mental health status arising after critical illness (PMID: 22809904)

2. Prevalence: 50% of ICU survivors experience at least one PICS domain; 25% experience impairments in multiple domains (PMID: 32413325)

3. BRAIN-ICU Landmark: Delirium duration is independently associated with long-term cognitive impairment - each additional day increases odds by 10% (PMID: 24088092)

4. Risk Factors: Delirium, sepsis, ARDS, longer ICU stay, mechanical ventilation, benzodiazepine sedation, immobility, older age, pre-existing cognitive impairment

5. PICS-F Impact: 30-40% of family caregivers experience significant psychological morbidity, sometimes exceeding patient burden (PMID: 27637173)

6. ABCDEF Bundle: High compliance associated with reduced mortality (68% decrease), increased ventilator-free days, and reduced delirium (PMID: 30243230)

7. Early Mobilisation: Reduces ICU-acquired weakness, improves functional outcomes at hospital discharge, and may reduce long-term physical PICS (PMID: 19446324)

8. ICU Diaries: Reduce PTSD symptoms and help patients reconstruct ICU memories, addressing psychological PICS (PMID: 20152764)

9. Follow-Up Clinics: Limited evidence for mortality or quality of life improvement; may benefit psychological outcomes (PMID: 30383141)

10. Recovery Trajectory: Most improvement occurs in first 6-12 months, but deficits persist for years - only 50-60% return to work by 12 months (PMID: 28490074)

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Definition and Epidemiology

Definition

Post-Intensive Care Syndrome (PICS) was defined by the Society of Critical Care Medicine (SCCM) in 2010 as new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond the acute care hospitalisation (PMID: 22809904). This consensus definition emerged from a multidisciplinary conference recognising that survival alone was an inadequate measure of ICU success.

The term PICS-F (PICS-Family) was subsequently introduced to describe the psychological impact on family members and caregivers, acknowledging that critical illness affects the entire family unit (PMID: 27637173).

Key definitional elements:

• New or worsening: Excludes pre-existing stable conditions
• Persisting beyond hospitalisation: Not transient post-operative delirium or temporary weakness
• Three domains: Physical, cognitive, mental health (often overlapping)
• Critical illness: Not limited to specific diagnoses - applies to any ICU admission

Epidemiology

Overall Prevalence:

• 50% of ICU survivors experience at least one PICS domain at hospital discharge (PMID: 32413325)
• 25% experience impairments in two or more domains (PMID: 28490074)
• Prevalence remains 30-40% at 12 months post-discharge (PMID: 24088092)

Domain-Specific Prevalence:

Australian/NZ Specific Data:

• ANZICS-CORE registry demonstrates similar PICS prevalence to international cohorts (PMID: 29940492)
• Australian ICU survivors show 40% reduction in health-related quality of life at 12 months (PMID: 26329724)
• Indigenous Australians face additional barriers to post-ICU rehabilitation including geographic isolation and healthcare access (PMID: 32895893)

COVID-19 Impact:

• COVID-19 ICU survivors demonstrate particularly high PICS rates (60-70%) (PMID: 33246471)
• Prolonged mechanical ventilation, isolation, and sedation contribute to increased burden
• "Long COVID" overlaps with traditional PICS in many domains

Mortality Context:

• 1-year mortality after ICU admission: 20-35% depending on population (PMID: 22449884)
• Among survivors, quality of life often reduced for years (PMID: 28490074)
• Return to work: 50-60% by 12 months (PMID: 22449884)

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Applied Basic Sciences

Pathophysiology of Physical PICS

ICU-Acquired Weakness (ICUAW):

ICUAW represents the physical domain of PICS and encompasses both critical illness polyneuropathy (CIP) and critical illness myopathy (CIM), often coexisting as critical illness polyneuromyopathy (CIPNM) (PMID: 25142814).

Mechanisms:

1. Muscle proteolysis: Upregulation of ubiquitin-proteasome pathway, autophagy-lysosomal system, and calpain activation leading to accelerated muscle breakdown (PMID: 24108526)
2. Impaired protein synthesis: Reduction in IGF-1, growth hormone resistance, anabolic resistance
3. Mitochondrial dysfunction: Reduced ATP production, oxidative stress, impaired biogenesis
4. Ion channel dysfunction: Sodium channel inactivation causing membrane inexcitability
5. Microvascular changes: Endothelial dysfunction, capillary leak, tissue oedema
6. Immobility: Mechanical unloading leads to 2-3% muscle loss per day (PMID: 24108526)

Risk Factors for ICUAW:

• Sepsis and systemic inflammation (OR 2.5-4.0)
• Duration of mechanical ventilation
• Hyperglycemia
• Corticosteroid use (controversial)
• Neuromuscular blocking agents (duration-dependent)
• Aminoglycoside use
• Immobility (most modifiable factor)
• Pre-existing frailty

Puthucheary Muscle Wasting Study (PMID: 24108526):

• Prospective cohort of 63 mechanically ventilated patients
• Rectus femoris cross-sectional area decreased 17.7% by day 10
• Greater wasting in multi-organ failure patients
• Muscle protein breakdown increased 2-3 fold
• Early mobilisation attenuated but did not prevent wasting

Pathophysiology of Cognitive PICS

Neuroinflammation: The brain is vulnerable to systemic inflammation through multiple mechanisms (PMID: 23915137):

1. Blood-brain barrier disruption: Systemic inflammation increases BBB permeability, allowing cytokines and inflammatory cells to enter CNS
2. Microglial activation: Resident brain macrophages become activated, releasing pro-inflammatory mediators
3. Neuronal injury: Direct cytokine toxicity, oxidative stress, excitotoxicity
4. Hippocampal vulnerability: Memory formation centres particularly susceptible to inflammatory injury

BRAIN-ICU Study Findings (PMID: 24088092):

• 821 patients with respiratory failure or shock assessed at 3 and 12 months
• 74% had delirium during ICU stay (median duration 4 days)
• At 3 months: 40% had cognitive scores similar to moderate TBI, 26% similar to mild Alzheimer's
• At 12 months: 34% had scores similar to moderate TBI, 24% similar to mild Alzheimer's
• Key finding: Each additional day of delirium associated with 10% increased odds of cognitive impairment at 12 months
• Severity of illness and sedation exposure also predictive

Hippocampal Atrophy: MRI studies demonstrate reduced hippocampal volume in ICU survivors with cognitive impairment (PMID: 23915137):

• 10-15% volume reduction compared to age-matched controls
• Correlates with memory deficits
• May be partially reversible with rehabilitation

Delirium as the Central Mediator: Delirium during ICU stay appears to be the strongest modifiable predictor of long-term cognitive impairment (PMID: 20231548):

• Not merely a marker of illness severity
• Independent predictor after adjusting for age, pre-existing cognition, sedation, severity
• Mechanism: aberrant neurotransmission (acetylcholine deficiency, dopamine excess), neuroinflammation, synaptic dysfunction

Pathophysiology of Mental Health PICS

PTSD Mechanisms:

• Traumatic ICU memories (procedural pain, delusional/hallucinatory experiences during delirium)
• Factual memory gaps leading to distress and rumination
• Hyperarousal from sympathetic activation during critical illness
• Sleep architecture disruption (PMID: 19050536)

Depression Mechanisms:

• Neuroinflammation-depression link (cytokine theory)
• Loss of independence and social role
• Chronic pain and fatigue
• Adjustment disorder to disability
• Survivor guilt (PMID: 19918375)

Anxiety Mechanisms:

• Fear of recurrence
• Health anxiety and hypervigilance
• Dependency on carers
• Financial and employment concerns

PICS-F Pathophysiology

Family members experience psychological distress through multiple pathways (PMID: 27637173):

1. Acute stress: Witnessing patient's critical illness, difficult surrogate decisions
2. Chronic stress: Prolonged caregiving, financial burden, role changes
3. Complicated grief: Even in survivors, families grieve for "the person who was"
4. Secondary traumatisation: Vicarious trauma from patient's experiences
5. Sleep deprivation: ICU environment, worry, caregiving demands

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Clinical Presentation

Physical Domain

ICU-Acquired Weakness:

• Generalised, symmetrical, flaccid weakness
• Typically spares facial muscles
• Respiratory muscle involvement prolongs weaning
• MRC sum score <48/60 diagnostic threshold
• Deep tendon reflexes: reduced (CIP) or normal (CIM)

Functional Decline:

• Reduced exercise capacity (6-minute walk distance 50-70% predicted at 12 months) (PMID: 28490074)
• Activities of daily living dependency (30-40% require assistance at discharge)
• Reduced grip strength
• Falls and fractures
• Weight loss and malnutrition

Fatigue:

• Most common physical complaint (70-80% of survivors)
• Disproportionate to measurable weakness
• Interferes with rehabilitation and return to activity
• Multifactorial: deconditioning, sleep disruption, depression, anaemia

Chronic Pain:

• Joint pain from immobility and positioning
• Neuropathic pain from critical illness polyneuropathy
• Procedural pain memories
• Chronic widespread pain syndrome

Frailty:

• Pre-existing frailty amplified by ICU admission
• New frailty in previously robust patients (PMID: 25171879)
• Clinical Frailty Scale (CFS) commonly increases 1-2 points
• Associated with increased mortality, readmission, institutionalisation

Cognitive Domain

Memory Deficits:

• Short-term memory most affected
• Difficulty learning new information
• Episodic memory gaps (inability to remember ICU stay)
• Working memory impairment

Executive Dysfunction:

• Difficulty planning and organising
• Impaired problem-solving
• Reduced cognitive flexibility
• Poor decision-making

Attention Deficits:

• Difficulty concentrating
• Increased distractibility
• Reduced sustained attention
• Impaired divided attention (multitasking)

Processing Speed:

• Slowed cognitive processing
• Delayed response times
• Mental fatigue with cognitive demands

Functional Impact:

• Difficulty managing medications
• Impaired driving ability
• Reduced work capacity
• Financial decision-making errors
• Medication non-adherence

Mental Health Domain

Post-Traumatic Stress Disorder (PTSD):

• Prevalence: 10-27% at 12 months (PMID: 19050536)
• Re-experiencing: Flashbacks, nightmares, intrusive memories of ICU
• Avoidance: Avoiding hospitals, medical appointments, reminders
• Hyperarousal: Sleep disturbance, irritability, hypervigilance
• Negative cognitions: Guilt, blame, detachment
• Delusional memories from delirium may be more distressing than factual memories

Depression:

• Prevalence: 25-35% at 12 months (PMID: 19918375)
• Often underdiagnosed (attributed to "normal" response to illness)
• Major depressive episode criteria met in many patients
• Associated with worse physical recovery and increased mortality
• Responds to standard treatments

Anxiety:

• Prevalence: 30-40% at 12 months
• Generalised anxiety disorder pattern common
• Health anxiety and fear of recurrence
• Panic attacks (especially related to dyspnoea in ARDS survivors)
• Social anxiety (embarrassment about disability)

Overlap:

• 50% of patients with PTSD also have depression
• Anxiety commonly comorbid with both
• Consider comprehensive mental health assessment

PICS-F Presentation

Anxiety:

• 70% of caregivers during ICU stay
• 30-40% persisting at 6-12 months
• Worry about patient's health and recurrence
• Financial and role-change anxiety

Depression:

• 30-35% of caregivers at 6-12 months
• Caregiver burden and exhaustion
• Social isolation
• Role loss (spouse becomes carer)

PTSD:

• 30% of family members at 12 months
• May exceed patient PTSD rates
• Traumatic memories of patient's critical illness
• Guilt about decisions made as surrogate

Complicated Grief:

• Even in survivors, families grieve for lost abilities and roles
• Anticipatory grief during ICU stay
• Chronic sorrow

Caregiver Burden:

• Physical demands of caring
• Time commitment (average 8-10 hours/day)
• Employment impact (50% reduce work hours)
• Financial strain

Sleep Disturbance:

• Common during and after ICU stay
• Hypervigilance about patient
• Fragmented sleep due to caregiving

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Risk Factors

Risk Factors by Domain

Modifiable vs Non-Modifiable Risk Factors

Non-Modifiable:

• Age
• Pre-existing cognitive impairment
• Prior psychiatric history
• Genetic susceptibility (APOE genotype)
• Admission diagnosis severity

Modifiable:

• Delirium (prevention and duration)
• Sedation depth and choice (avoid benzodiazepines)
• Immobility (early mobilisation)
• Hypoglycemia and hyperglycemia
• Sleep disruption
• Pain management
• Family involvement
• ICU environment (noise, light)

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Patients:

• Higher prevalence of sepsis (1.5-2x) and critical illness (PMID: 32895893)
• Pre-existing comorbidities increase PICS risk
• Geographic isolation limits rehabilitation access
• Cultural factors affect family involvement and decision-making
• Aboriginal Health Workers (AHWs) should be involved in care planning
• Aboriginal Liaison Officers (ALOs) facilitate culturally appropriate follow-up

Maori Health Considerations:

• Higher rates of critical illness admission
• Whanau (extended family) central to recovery support
• Cultural beliefs may influence acceptance of rehabilitation
• Maori Health Workers should be engaged
• Te Whare Tapa Wha model of health (physical, mental, spiritual, family)

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Investigations

Assessment of Physical PICS

Muscle Strength Testing:

• Medical Research Council (MRC) sum score: 0-60 (12 muscle groups bilaterally)
• ICUAW defined as MRC sum score <48 or handgrip strength <11 kg (men) / <7 kg (women)
• Requires patient cooperation (may be limited by delirium/sedation)

Functional Assessment:

• 6-Minute Walk Test (6MWT): Gold standard for functional capacity
• Timed Up and Go (TUG): Mobility and fall risk
• Barthel Index: Activities of daily living
• Functional Independence Measure (FIM): Comprehensive functional status
• Short Physical Performance Battery (SPPB): Balance, gait, strength

Frailty Assessment:

• Clinical Frailty Scale (CFS): 1-9 scale (PMID: 25171879)
• Fried Frailty Phenotype: Weight loss, exhaustion, low activity, slow gait, weak grip
• Edmonton Frail Scale

Electrophysiology (if diagnostic uncertainty):

• Nerve conduction studies: Reduced CMAP amplitudes in CIP
• Electromyography: Myopathic changes in CIM
• Not routinely required for clinical management

Assessment of Cognitive PICS

Screening Tools:

• Montreal Cognitive Assessment (MoCA): 30-point scale, <26 suggests impairment
• Mini-Mental State Examination (MMSE): Less sensitive to executive dysfunction
• Clock Drawing Test: Executive function screen

Comprehensive Neuropsychological Testing:

• Memory (verbal and visual)
• Executive function (Trail Making, Wisconsin Card Sorting)
• Attention (Digit Span, Continuous Performance)
• Processing speed (Symbol Digit Modalities)
• Language (Boston Naming Test)

Imaging (research and selected cases):

• MRI brain: Hippocampal atrophy, white matter changes
• Diffusion tensor imaging: White matter tract integrity

Assessment of Mental Health PICS

PTSD Screening:

• Impact of Event Scale-Revised (IES-R): 22 items, ≥33 suggests PTSD
• PTSD Checklist (PCL-5): DSM-5 aligned, ≥31-33 cutoff
• Clinical interview for definitive diagnosis

Depression Screening:

• Hospital Anxiety and Depression Scale (HADS): Validated in medical populations
• Patient Health Questionnaire-9 (PHQ-9): ≥10 moderate depression
• Beck Depression Inventory (BDI-II)

Anxiety Screening:

• HADS-Anxiety subscale
• Generalised Anxiety Disorder-7 (GAD-7)

Comprehensive Assessment:

• Psychiatric evaluation for complex cases
• Suicide risk assessment in depressed patients
• Consideration of substance use (self-medication)

Assessment of PICS-F

Caregiver-Specific Tools:

• Zarit Burden Interview: Caregiver strain and burden
• HADS: Anxiety and depression in caregivers
• IES-R: PTSD symptoms in caregivers
• Caregiver Quality of Life Index-Cancer (adapted): Overall wellbeing

Quality of Life:

• SF-36 or EQ-5D for patient and caregiver
• ICU Memory Tool: Factual, emotional, delusional memory assessment

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Prevention Strategies

ABCDEF Bundle

The ABCDEF Bundle (also called ICU Liberation Bundle) is the primary evidence-based strategy for PICS prevention (PMID: 30243230).

A - Assess, Prevent, and Manage Pain:

• Routine pain assessment using validated scales (BPS, CPOT for non-verbal patients)
• Analgesia-first approach before escalating sedation
• Multimodal analgesia to reduce opioid requirements
• Consider regional techniques where appropriate

B - Both Spontaneous Awakening Trials (SAT) and Spontaneous Breathing Trials (SBT):

• Daily SAT: Interrupt sedation to allow awakening (unless contraindicated)
• Daily SBT: Assess readiness for extubation
• Paired SAT-SBT improves outcomes (ABC Trial, PMID: 18198532)
• Reduces duration of mechanical ventilation and ICU stay

C - Choice of Analgesia and Sedation:

• Avoid benzodiazepines: Associated with increased delirium and cognitive PICS
• Prefer dexmedetomidine or propofol for sedation
• Target light sedation (RASS -1 to 0) rather than deep sedation
• Analgosedation approach: Treat pain first, then sedate if needed

D - Delirium: Assess, Prevent, and Manage:

• Routine screening (CAM-ICU or ICDSC) at least twice daily
• Non-pharmacological prevention: Sleep promotion, reorientation, early mobilisation, family presence, hearing aids/glasses
• Avoid deliriogenic medications (benzodiazepines, anticholinergics)
• No pharmacological prophylaxis proven effective (PMID: 27376588)

E - Early Mobility and Exercise:

• Begin mobilisation within 24-48 hours of ICU admission when safe
• Progressive mobility protocol: Passive ROM → Active ROM → Sitting → Standing → Ambulation
• Physical therapy and occupational therapy involvement
• Can be performed even in mechanically ventilated patients (PMID: 19446324)
• Reduces ICUAW, delirium, and improves functional outcomes

F - Family Engagement and Empowerment:

• Open/flexible visitation policies
• Family participation in rounds and care activities
• Education about critical illness and recovery trajectory
• Emotional support for family members
• Introduction to PICS-F concept
• Advance care planning discussions

ABCDEF Bundle Evidence

Pun et al. 2019 (PMID: 30243230):

• Multicentre cohort of 15,226 patients across 68 ICUs
• Proportional compliance with bundle components assessed
• Key Findings:
  • "Full bundle compliance associated with:"
    • 68% lower odds of hospital death (OR 0.32)
    • Higher likelihood of next-day discharge from ICU (OR 1.39)
    • Reduced delirium and coma
    • More ventilator-free days
  • "Dose-response relationship: More components → better outcomes"
  • Each 10% increase in compliance associated with 15% reduction in mortality

Early Mobilisation Evidence

Schweickert et al. 2009 (PMID: 19446324):

• RCT of early physical and occupational therapy vs usual care
• 104 mechanically ventilated patients
• Intervention: Mobilisation within 72 hours, interruption of sedation
• Results:
  • "Return to independent functional status at discharge: 59% vs 35% (p=0.02)"
  • More ventilator-free days (23.5 vs 21.1, p=0.05)
  • Shorter delirium duration (2 vs 4 days, p=0.02)
  • No increase in adverse events

TEAM Trial 2022 (PMID: 36049438):

• Pragmatic RCT, 750 patients, 49 ICUs
• Higher-dose early mobilisation vs usual care
• Results:
  • No difference in 180-day survival (OR 1.01)
  • No difference in 6MWT at 180 days
  • Intervention group more likely to be out of bed (94% vs 87%)
  • May suggest ceiling effect or that usual care has improved

ICU Diaries

Concept:

• Diary kept by nurses, family, and visitors during ICU stay
• Documents daily events, progress, photos
• Given to patient after recovery
• Helps fill factual memory gaps and reduce delusional memory burden

Evidence: Jones et al. 2010 (PMID: 20152764):

• RCT of ICU diaries vs no intervention
• 352 patients across Europe
• New PTSD at 3 months: 5% (diary) vs 13% (control), p=0.02

RACHEL Trial 2023 (PMID: 36515349):

• RCT of ICU diaries in Australia/NZ
• 423 patients
• Primary outcome (PTSD at 6 months): No significant difference
• Limitations: High baseline diary use in control group, timing of diary introduction

Sleep Promotion

Non-Pharmacological:

• Cluster care activities to allow uninterrupted sleep
• Reduce noise (earplugs, alarm optimisation)
• Reduce light (eye masks, dimmed lighting)
• Maintain circadian rhythm (daytime light exposure)
• Minimise night-time interruptions

Pharmacological:

• Melatonin: Evidence inconclusive for delirium prevention but low risk
• Avoid benzodiazepines and anticholinergics for sleep

Family Engagement

Family Presence:

• Flexible/open visiting hours
• Family presence during procedures (when appropriate)
• Family participation in multidisciplinary rounds
• Family-delivered basic care (massage, oral care)

Communication:

• Regular family meetings (at least weekly, more if deteriorating)
• Consistent information from identified intensivist
• Written information about PICS and recovery
• Preparation for post-ICU trajectory

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Management

ICU Phase Management

During ICU Stay:

• ABCDEF Bundle implementation (see Prevention)
• Early identification of high-risk patients
• Begin ICU diary if available
• Family engagement and education
• Physiotherapy and occupational therapy involvement
• Speech pathology for swallowing assessment
• Nutritional optimization

Preparing for ICU Discharge:

• Rehabilitation assessment and goal-setting
• Family education about expected trajectory
• Medication reconciliation
• Follow-up arrangements
• Handover to ward team with PICS risk summary

Ward Phase Management

Continued Rehabilitation:

• Progressive mobilisation
• Nutritional support
• Cognitive screening
• Psychological support if needed
• Sleep hygiene

Discharge Planning:

• Destination: Home, rehabilitation, aged care
• Home modifications if needed
• Equipment provision
• Community services referral
• GP communication
• Follow-up appointments

Post-Hospital Management

Physical Rehabilitation:

• Outpatient physiotherapy
• Cardiac or pulmonary rehabilitation programs
• Graduated exercise prescription
• Falls prevention
• Assistive device training

Cognitive Rehabilitation:

• Cognitive rehabilitation therapy
• Compensatory strategies (memory aids, routines)
• Occupational therapy for functional strategies
• Speech pathology for communication/cognition
• Return to driving assessment

Mental Health Treatment:

• PTSD: Trauma-focused CBT, EMDR
• Depression: CBT, medication (SSRIs)
• Anxiety: CBT, relaxation training
• Psychiatric referral for complex cases
• Support groups for ICU survivors

PICS-F Support:

• Family counseling
• Respite services
• Carers' support groups
• Financial counseling
• Ongoing communication with treating team

ICU Follow-Up Clinics

Concept: Dedicated clinics for ICU survivors, typically 2-3 months post-discharge, providing:

• Medical review by intensivist/nurse practitioner
• Screening for all PICS domains
• Onward referral to rehabilitation services
• Psychological support
• Family review
• Medication review

Australian/NZ Context:

• Limited number of dedicated ICU follow-up clinics
• Some integrated into respiratory or rehabilitation services
• ANZICS-CORE supports outcomes research but no mandated follow-up structure
• Rural and regional patients face access barriers

Evidence: The evidence for ICU follow-up clinics is disappointing (Cochrane Review, PMID: 30383141):

• No clear benefit for mortality at 12 months
• No clear benefit for health-related quality of life
• Possible benefit for psychological outcomes (PTSD reduction) (PMID: 24523301)
• High heterogeneity in clinic models
• May be too late (2-3 months) to influence recovery trajectory

RETURN Trial (PMID: 29166298):

• RCT of nurse-led ICU follow-up consultations vs usual care
• 272 patients, UK
• No difference in quality of life at 12 months
• No difference in anxiety, depression, PTSD
• Suggests consultation alone insufficient without targeted rehabilitation

Implications:

• Follow-up clinics provide patient/family satisfaction and continuity
• May be better as "screening" to identify those needing intervention
• Multi-professional approach may be more effective (PMID: 33246471)
• Earlier intervention (during hospitalisation) may have more impact

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Prognosis and Outcomes

Physical Outcomes

ICU-Acquired Weakness:

• Majority improve over 6-12 months
• 25-30% have persistent weakness at 12 months
• Full recovery in only 50-70% (PMID: 25142814)
• Proximal weakness tends to improve more than distal

Functional Outcomes:

• 6-minute walk distance: 50-70% predicted at 12 months
• 30-40% of ARDS survivors cannot return to work at 12 months (PMID: 28490074)
• 50% require assistance with ADLs at hospital discharge
• 20-30% remain dependent at 12 months

Frailty:

• New or worsened frailty common
• Frailty associated with increased mortality and institutionalisation
• May be partially reversible with rehabilitation

Cognitive Outcomes

BRAIN-ICU Findings (PMID: 24088092):

• 3 months: 40% with cognitive impairment (26% severe)
• 12 months: 34% with cognitive impairment (24% severe)
• Deficits comparable to mild TBI or early Alzheimer's
• Affects patients of all ages (not just elderly)
• Independent of pre-existing cognitive status

Trajectory:

• Some improvement in first 6-12 months
• Plateau or minimal improvement thereafter
• 15-25% have persistent deficits at 5 years
• Executive function may improve less than memory

Mental Health Outcomes

PTSD (PMID: 19050536):

• Point prevalence 10-27% at 3-24 months
• May be delayed onset (emergence months after discharge)
• Delusional ICU memories predict worse outcomes
• Responds to trauma-focused therapy

Depression (PMID: 19918375):

• Point prevalence 25-35% at 12 months
• Often comorbid with anxiety and PTSD
• Associated with worse physical recovery
• Responds to standard treatments

Anxiety:

• Point prevalence 30-40% at 12 months
• Health anxiety particularly common
• May persist longer than depression

PICS-F Outcomes

Family Member Psychological Burden:

• Anxiety: 70% during ICU, 30-40% at 12 months
• Depression: 30-35% at 12 months
• PTSD: 30% at 12 months
• May persist for years

Caregiving Impact:

• Average 8-10 hours/day caregiving in first months
• 50% reduce work hours or leave employment
• Marital stress in 20-30%
• Financial strain common

Mortality

Post-ICU Mortality:

• 1-year mortality: 20-35% (depending on population) (PMID: 22449884)
• 5-year mortality: 40-50% in some cohorts
• Excess mortality compared to general population persists for years
• PICS itself may contribute through depression, reduced adherence, functional decline

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Australian/NZ Context

Healthcare System Considerations

Rehabilitation Pathways:

• Inpatient rehabilitation for severe impairment (CFS increase >2)
• Transitional care programs
• Hospital in the Home services
• Outpatient rehabilitation (limited access in rural areas)
• Community-based rehabilitation

State-Based Services:

• NSW: ACI Physiotherapy-led ICU rehabilitation programs
• Victoria: Some hospitals with dedicated ICU follow-up
• Queensland: Integrated rehabilitation services
• NZ: Limited ICU-specific follow-up, rehabilitation through DHBs

Access Barriers:

• Geographic isolation (rural and remote patients)
• Indigenous health service gaps
• Private vs public funding
• Limited ICU-specific rehabilitation expertise

ANZICS-CORE Registry

The ANZICS Centre for Outcome and Resource Evaluation (CORE) provides:

• Benchmarking of ICU outcomes across Australia/NZ
• Risk-adjusted mortality and length of stay comparisons
• Research platform for outcomes studies
• Quality improvement support

Relevance to PICS:

• Increasing focus on patient-centred outcomes beyond mortality
• PRO-ICU (Patient Reported Outcomes in ICU) initiative
• Support for follow-up studies

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Patients:

• Higher critical illness burden (sepsis, trauma, diabetic complications)
• Pre-existing comorbidities increase PICS risk
• Involve Aboriginal Health Workers in rehabilitation planning
• Aboriginal Liaison Officers facilitate culturally appropriate care
• Consider telehealth for remote follow-up
• Family-centred care aligns with Indigenous values
• Acknowledge connection to Country in recovery context

Maori Health Considerations:

• Higher ICU admission rates
• Whanau (extended family) integral to recovery
• Maori Health Workers should be engaged
• Te Whare Tapa Wha holistic health model:
  • Taha tinana (physical)
  • Taha hinengaro (mental/emotional)
  • Taha whanau (family/social)
  • Taha wairua (spiritual)
• This model aligns well with PICS domains

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SAQ Practice Questions

SAQ 1: PICS Domains and Prevention (20 marks)

Question: A 48-year-old previously fit man is in your ICU with severe community-acquired pneumonia requiring mechanical ventilation for 10 days. He has experienced intermittent delirium (CAM-ICU positive on 6 days). He is now awake, off sedation, and preparing for extubation.

a) Define Post-Intensive Care Syndrome (PICS) and outline its three domains (4 marks) b) Identify risk factors in this case for each PICS domain (6 marks) c) Describe evidence-based prevention strategies you would implement before and after ICU discharge (6 marks) d) Outline how you would assess for PICS at an outpatient follow-up visit 3 months post-discharge (4 marks)

Model Answer:

(a) Definition and Domains (4 marks)

PICS is defined as new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond acute care hospitalisation (SCCM 2010, PMID: 22809904).

Three domains:

1. Physical: ICU-acquired weakness, reduced functional capacity, fatigue, chronic pain, frailty
2. Cognitive: Memory deficits, executive dysfunction, attention impairment, processing speed reduction
3. Mental Health: PTSD, depression, anxiety

(Award 1 mark for definition, 1 mark for each domain correctly described)

(b) Risk Factors by Domain (6 marks)

Physical:

• 10 days mechanical ventilation (immobility, muscle wasting)
• Severe sepsis (systemic inflammation, catabolism)
• Likely corticosteroid exposure
• Prolonged ICU stay

Cognitive:

• Delirium on 6 days (BRAIN-ICU: strongest predictor) (PMID: 24088092)
• Hypoxia from respiratory failure
• Sepsis-associated encephalopathy
• Potential sedative exposure (especially if benzodiazepines used)

Mental Health:

• Prolonged ICU stay with limited family contact
• Delirium (delusional memories predict PTSD)
• Previously fit (adjustment to disability)
• Potential for traumatic ICU memories

(Award 2 marks per domain: 1 for listing factors, 1 for explanation/evidence)

(c) Prevention Strategies (6 marks)

Before ICU Discharge:

• ABCDEF bundle implementation (PMID: 30243230)
  • "A: Optimise analgesia"
  • "B: SAT/SBT completed (now extubating)"
  • "C: Avoid benzodiazepines for ongoing sedation"
  • "D: Continue delirium monitoring post-extubation"
  • "E: Early mobilisation - physiotherapy, OT involvement"
  • "F: Family engagement, education about PICS, ICU diary review"
• Cognitive orientation (calendars, clocks, family photos)
• Sleep promotion (noise reduction, lighting)
• Nutritional optimisation
• Early ICU diary review if available

After ICU Discharge:

• Ward-based rehabilitation continuation
• Discharge planning with GP communication about PICS
• Family education about expected recovery trajectory
• Mental health screening before hospital discharge
• Referral to outpatient rehabilitation if persistent weakness
• Follow-up arrangements (ICU clinic or equivalent)
• Written information for patient and family

(Award 3 marks for ICU strategies, 3 marks for post-ICU strategies)

(d) 3-Month Assessment (4 marks)

Physical:

• MRC sum score or handgrip dynamometry
• 6-Minute Walk Test (6MWT)
• Functional Independence Measure (FIM) or Barthel Index
• Return to work/ADL status

Cognitive:

• Montreal Cognitive Assessment (MoCA) - screen for <26
• Specific domains: memory, executive function, attention
• Functional impact: medication management, driving, work capacity

Mental Health:

• Hospital Anxiety and Depression Scale (HADS) or PHQ-9/GAD-7
• Impact of Event Scale-Revised (IES-R) for PTSD
• Sleep quality assessment
• Suicide risk screen if depressed

PICS-F:

• Ask about caregiver burden and wellbeing
• Zarit Burden Interview if indicated
• HADS for primary caregiver

(Award 1 mark each for physical, cognitive, mental health, and PICS-F assessment)

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SAQ 2: BRAIN-ICU and Delirium Evidence (20 marks)

Question: You are giving a teaching session to ICU trainees on the relationship between delirium and long-term cognitive outcomes.

a) Summarise the key findings of the BRAIN-ICU study (PMID: 24088092) (6 marks) b) Explain the pathophysiological mechanisms linking ICU delirium to long-term cognitive impairment (4 marks) c) Describe evidence-based strategies to prevent delirium in the ICU (6 marks) d) Critically appraise the evidence for pharmacological delirium prevention (4 marks)

Model Answer:

(a) BRAIN-ICU Study Summary (6 marks)

Design:

• Prospective cohort study, 821 patients
• Respiratory failure or shock requiring ICU admission
• Medical and surgical ICUs, USA
• Published: NEJM 2013 (Pandharipande et al.)

Methods:

• Daily delirium assessment (CAM-ICU)
• Cognitive testing at 3 and 12 months using validated batteries
• Global cognition score compared to normative data

Key Findings:

1. 74% experienced delirium during ICU stay (median 4 days)
2. At 3 months:
   • 40% had cognitive scores 1.5 SD below population mean
   • 26% had scores similar to mild Alzheimer's disease
3. At 12 months:
   • 34% had persistent cognitive impairment
   • 24% remained in severe impairment range
4. Critical finding: Each additional day of delirium associated with 10% increased odds of cognitive impairment at 12 months
5. Association independent of:
   • Age
   • Pre-existing cognitive impairment
   • Severity of illness (APACHE II)
   • Sedative exposure
6. Both younger and older patients affected (not just elderly)

Clinical Implications:

• Delirium is not benign - has lasting consequences
• Prevention of delirium is a priority
• Duration of delirium is dose-dependent for cognitive harm

(Award marks for design [1], methods [1], key findings [3], clinical implications [1])

(b) Pathophysiological Mechanisms (4 marks)

Neuroinflammation:

• Systemic inflammation (sepsis, surgery) activates microglia
• Cytokines cross blood-brain barrier (increased permeability)
• TNF-α, IL-1β, IL-6 directly neurotoxic
• Oxidative stress and mitochondrial dysfunction

Neurotransmitter Dysregulation:

• Acetylcholine deficiency (anticholinergic burden)
• Dopamine excess (explaining hyperactive features)
• GABA dysregulation (explaining sedative sensitivity)
• Glutamate excitotoxicity

Hippocampal Vulnerability:

• Memory formation centre highly susceptible
• MRI studies show hippocampal atrophy in ICU survivors (PMID: 23915137)
• 10-15% volume reduction correlates with memory deficits

Metabolic Derangements:

• Hypoxia, hypoglycemia, hypercapnia
• Electrolyte disturbances
• Organ dysfunction (renal, hepatic)

Synaptic Dysfunction:

• Impaired long-term potentiation
• Dendritic pruning
• Reduced brain-derived neurotrophic factor (BDNF)

(Award 1 mark each for any 4 well-explained mechanisms)

(c) Evidence-Based Delirium Prevention (6 marks)

ABCDEF Bundle Components (PMID: 30243230):

• Reduce sedation depth (RASS -1 to 0 target)
• Daily awakening trials (SAT)
• Avoid benzodiazepines (prefer dexmedetomidine or propofol)
• Early mobility and exercise
• Family presence and reorientation

Environmental Modifications:

• Natural light exposure during daytime
• Reduce nocturnal noise and light
• Cluster care activities for uninterrupted sleep
• Earplugs and eye masks (low-cost interventions)
• Maintain day-night cycle

Cognitive Orientation:

• Clocks and calendars visible
• Family photos and familiar objects
• Regular reorientation by staff
• Hearing aids and glasses if needed
• Consistent care team

Pharmacological Considerations:

• Avoid deliriogenic medications:
  • Benzodiazepines
  • Anticholinergics
  • Opioids (minimise, not eliminate)
• Treat underlying causes (pain, infection, hypoxia, constipation)

Evidence:

• ABCDEF bundle: 50% reduction in delirium incidence when fully implemented
• Each component contributes; more components → better outcomes

(Award marks for pharmacological [2], environmental [2], bundle/behavioural [2])

(d) Critical Appraisal of Pharmacological Prophylaxis (4 marks)

Antipsychotics:

• HOPE-ICU (haloperidol): No effect on delirium-free survival (PMID: 23695224)
• AID-ICU (haloperidol): No effect on days alive without delirium/coma (PMID: 35709104)
• REDUCE (haloperidol): No effect on delirium duration (PMID: 29768152)
• Conclusion: No evidence to support routine antipsychotic prophylaxis

Dexmedetomidine:

• MENDS2 (dexmedetomidine vs propofol): No difference in delirium-free days (PMID: 33755458)
• May reduce delirium vs benzodiazepines but not vs propofol
• Role more in sedation choice than prophylaxis

Melatonin:

• Multiple small trials with mixed results
• Cochrane review: Insufficient evidence (PMID: 33779817)
• Low risk, may have modest benefit for sleep

Statins, Ketamine:

• No convincing evidence for prophylaxis

Current Guidelines:

• No pharmacological agent recommended for routine prophylaxis
• Focus should be on non-pharmacological bundle approach
• Treat delirium when present (antipsychotics have modest evidence for treatment)

(Award marks for antipsychotic trials [2], other agents [1], guideline conclusion [1])

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Viva Scenarios

Viva 1: ABCDEF Bundle and Family-Centred Care

Setting: Post-exam viva, CICM Second Part

Examiner: "A 62-year-old woman has been in your ICU for 8 days with pancreatitis complicated by ARDS. She is sedated with propofol and fentanyl, RASS -2, mechanically ventilated on PSV, FiO2 0.40. Her husband is very anxious and wants to know what you're doing to prevent long-term problems after ICU."

Candidate Response:

"This is an important question from the family, and I'm pleased he's thinking about recovery beyond just survival. I would explain that we're implementing multiple strategies to prevent what we call Post-Intensive Care Syndrome or PICS."

Examiner: "What is PICS and what are its domains?"

"PICS encompasses new or worsening impairments in three domains after critical illness:

1. Physical - weakness, fatigue, reduced function
2. Cognitive - memory problems, concentration difficulties
3. Mental health - PTSD, depression, anxiety

About 50% of ICU survivors experience problems in at least one domain. I would also mention that family members can develop what we call PICS-F - psychological distress including anxiety, depression, and PTSD - so his wellbeing matters too."

Examiner: "What specific strategies are you using in this patient?"

"We're implementing the ABCDEF bundle, which has the strongest evidence for reducing these problems.

A - Pain assessment and management: Using the CPOT scale since she's sedated, ensuring adequate analgesia before assessing sedation needs.

B - Both SAT and SBT: We'll perform daily spontaneous awakening trials by interrupting sedation to assess wakefulness, paired with spontaneous breathing trials to assess extubation readiness.

C - Choice of sedation: We're using propofol rather than benzodiazepines, as benzodiazepines are strongly associated with delirium and worse cognitive outcomes. We're targeting light sedation, RASS -1 to 0.

D - Delirium monitoring: Once awake enough for assessment, we'll use CAM-ICU twice daily. We're already implementing prevention through light sedation, mobilisation, and environmental modifications.

E - Early mobility: Physiotherapy is involved. Even now on the ventilator, we can do passive range of motion and chair positioning when stable.

F - Family engagement: This is exactly what we're doing now. I'd invite her husband to participate in care, visit flexibly, and we have an ICU diary he could contribute to."

Examiner: "Tell me about the evidence for the ABCDEF bundle."

"The strongest evidence comes from Pun et al. in Lancet Respiratory Medicine 2019 (PMID: 30243230). This was a multicentre cohort of over 15,000 patients across 68 ICUs. They found a dose-response relationship - more bundle components implemented, better outcomes.

Key findings:

• Full compliance associated with 68% lower odds of hospital death
• Increased likelihood of next-day ICU discharge
• More ventilator-free days
• Reduced delirium and coma

Each 10% increase in bundle compliance was associated with 15% reduction in mortality."

Examiner: "The family asks about ICU diaries. What would you tell them?"

"ICU diaries are a low-cost intervention where staff and family document daily events, progress, and photos during the ICU stay. The diary is given to the patient after recovery.

The concept is that patients often have fragmented or absent memories of ICU, and sometimes delusional memories from delirium that can be distressing. The diary helps fill factual memory gaps and can help distinguish real from delusional memories.

The original evidence from Jones et al. 2010 (PMID: 20152764) showed reduction in PTSD from 13% to 5% at 3 months. However, a recent Australian-New Zealand trial, the RACHEL trial, didn't show significant benefit, possibly because diary use in control groups has become more common.

I'd still encourage the family to participate in a diary if available - it's safe, low-cost, and valued by patients and families even if the PTSD benefit is uncertain."

Examiner: "What specific things would you discuss with this anxious husband about PICS-F?"

"I would:

1. Validate his anxiety - It's completely normal to be worried in this situation
2. Educate - Explain that 30-40% of family members experience significant psychological distress that can persist for months
3. Normalise - His feelings are shared by many ICU families
4. Encourage self-care - Sleep, eating, taking breaks, maintaining social connections
5. Involve him in care - Family involvement helps both patient and family outcomes
6. Provide resources - Written information, social work referral, chaplaincy if appropriate
7. Plan follow-up - He should look after his own mental health; GP involvement may be needed
8. Consider formal screening - If distress is severe, psychiatric or psychology referral

I'd emphasise that by looking after himself, he'll be better able to support his wife's recovery."

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Viva 2: Cognitive Impairment and Follow-Up

Setting: CICM Second Part Viva

Examiner: "A 55-year-old teacher is referred to your ICU follow-up clinic 3 months after a 14-day ICU stay for septic shock with ARDS. He required mechanical ventilation for 10 days and had persistent delirium. He says he can't remember much about ICU, has trouble concentrating at work, and hasn't been able to return to teaching."

Candidate Response:

"This presentation is concerning for cognitive PICS. Given his prolonged delirium, mechanical ventilation, and sepsis, he was high-risk for long-term cognitive impairment. His symptoms of memory problems and concentration difficulties affecting work are typical of cognitive PICS."

Examiner: "How would you assess him?"

"I would perform a structured assessment of all PICS domains:

Cognitive assessment:

• Montreal Cognitive Assessment (MoCA) as a screening tool - score <26 suggests impairment
• Specific domains to assess: memory (both recall and recognition), executive function, attention, processing speed
• Functional impact: Can he manage medications? Drive safely? Handle finances?
• For formal diagnosis and rehabilitation planning, I'd refer to neuropsychology

Physical assessment:

• Handgrip strength
• 6-Minute Walk Test if feasible
• Functional status (ADLs, employment, exercise tolerance)
• Fatigue assessment

Mental health assessment:

• PHQ-9 for depression (his concentration problems could partly be depression)
• GAD-7 for anxiety
• IES-R or PCL-5 for PTSD
• Sleep quality
• Suicide risk if depression present

PICS-F:

• How is his family coping?
• Caregiver burden on spouse/partner?"

Examiner: "His MoCA is 22/30, with deficits in delayed recall and attention. What would you tell him about the BRAIN-ICU study?"

"I would explain that we now understand much more about why ICU survivors have cognitive problems, thanks to a landmark study called BRAIN-ICU by Pandharipande and colleagues.

I'd tell him:

1. He's not alone - About 40% of ICU survivors at 3 months and 34% at 12 months have significant cognitive impairment
2. Delirium is the key predictor - The study found that each additional day of delirium increased the odds of long-term cognitive problems by 10%. His prolonged delirium put him at particularly high risk
3. Age doesn't matter as much as expected - Even younger, previously healthy people are affected
4. It's not just 'confusion clearing' - The deficits can be as severe as mild Alzheimer's disease
5. The brain is injured - MRI studies show actual changes like hippocampal atrophy, which explains the memory problems
6. There is hope for improvement - Most improvement occurs in the first 6-12 months, but some recovery can continue beyond this"

Examiner: "What treatments would you recommend?"

"Unfortunately, we don't have highly effective treatments for established cognitive PICS, which is why prevention is so important. However, I would recommend:

Cognitive rehabilitation:

• Referral to neuropsychology for formal assessment and rehabilitation strategies
• Occupational therapy for functional strategies
• Memory aids: calendars, phone reminders, routines
• Cognitive exercises (though evidence is limited)

Address modifiable factors:

• Treat depression if present (can worsen cognition)
• Ensure adequate sleep
• Optimise cardiovascular risk factors
• Regular exercise (has cognitive benefits)
• Social engagement

Work considerations:

• Graduated return to work if possible
• Workplace accommodations (reduced hours, simplified tasks initially)
• May need formal occupational assessment
• Teaching requires significant cognitive demands - may need role modification

Follow-up:

• Repeat assessment at 6-12 months
• If no improvement, formal neurological review
• Consider driving assessment if safety concerns

I would also manage expectations - while some improvement is expected, full recovery to pre-ICU baseline is not guaranteed, and he may need to adapt his work and life accordingly."

Examiner: "What's the evidence for ICU follow-up clinics improving outcomes?"

"The evidence is actually disappointing. The Cochrane review by Schofield-Robinson in 2018 (PMID: 30383141) found no clear evidence that ICU follow-up services reduced mortality or improved health-related quality of life compared to usual care.

Similarly, the RETURN trial by Walsh in 2015 (PMID: 29166298) - a UK RCT of nurse-led ICU follow-up - showed no difference in quality of life, anxiety, depression, or PTSD at 12 months.

However, there are some nuances:

1. Meta-analyses suggest possible benefit for psychological outcomes, particularly PTSD symptoms (PMID: 24523301)
2. Clinics are highly valued by patients and families for continuity and 'closure'
3. Multi-professional approaches may be more effective than simple consultation (PMID: 33246471)
4. The main value may be screening to identify those who need intervention rather than the clinic itself providing treatment

The problem is that most clinics occur 2-3 months post-discharge, which may be too late to influence the recovery trajectory that's largely set in the first weeks.

Despite this evidence, I think follow-up has value for patient satisfaction, education, medication review, and identifying the minority who need specific intervention. But we shouldn't expect the clinic visit itself to dramatically change outcomes."