Long-term Outcomes in Survivors of Complex Critical Illness and their Family Caregivers: Towards RECOVER Phase 1:The RECOVER Program

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Long-term Outcomes in Survivors of Complex
Critical Illness and their Family Caregivers
Towards RECOVER Phase 1The RECOVER Program

• Margaret Herridge MD MPH
• Professor of Medicine
• Scientist, Toronto General Research Institute
• Interdepartmental Division of Critical Care
• University of Toronto, Canadian Critical Care
  Trials Group

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Overview

• Spectrum of Disability
• Continuum of Weakness
• Cognitive Dysfunction and Mood Disorders
• RECOVER and risk stratification to optimize
  rehabilitation

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Evidence of diaphragmatic atrophy and increased
proteolysis at 18 hours of mechanical ventilation
De Jonghe, B. et al. JAMA 20022882859-2867 Ali
N et al. AJRCCM 2008 178261-268
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Herridge et al. N Engl J Med 2003 348683-93.
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• All biopsies were abnormal (6-24 months after ICU
  discharge)
• No patients were exposed to steroids or
  paralytics
• Most common abnormality was type II fiber atrophy
• Manifested as narrow angulated fibers myofibers
  were reduced to
• clumps of myonuclei
• Myofibrillary disarray on EM
• Changes not exclusively attributable to disuse
  atrophy

Angel et al. 2007 Can J Neurol Sci 34 427-432
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Five-Year Outcomes in ARDS Herridge et al. NEJM
2011 364 1293-304
Persistent exercise limitation and reduction in
Physical QOL at 5-years after ICU discharge
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• Heterotopic Ossification

Alopecia
Tracheal stenosis
Cosmesis- Scars from CVC, Art line, CT, drain
sites
Nerve and Muscle
Brain
Hearing Loss
Bronchiectasis
Pulmonary fibrosis
Taste changes
Weakness
Mental Health Cognition
frozen joints contractures
striae
Ischemic digits
Disability after Critical Illness
Renal Impairment
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Hopkins et al. AJRCCM 1999 16050 Hopkins et al.
J Int Neuropsych Assoc 20039584
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• Enrolment in a conservative fluid-management
  strategy was associated with
• cognitive impairment
• Lower partial pressure of oxygen was associated
  with cognitive and psychiatric
• impairment
• Hypoglycemia was associated with mood disorders

Am J Respir Crit Care Med 2012 1851307-13
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Pandharipande et al. NEJM 2013
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• Sepsis survivors had a reduction in verbal
  learning and memory
• Reduction in left hippocampal volume
• Increase in low frequency EEG activity consistent
  with brain dysfunction
• No clinical difference in HRQOL, psychological
  dysfunction, mood disorders

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Ischemic Changes
Brain Atrophy
Suchyta et al. Brain Imaging and Behavior
422-34, 2010
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Risk Factors for Cognitive Dysfunction

• Duration of Delirium
• Blood Glucose Dysregulation
• Conservative Fluid Management
• Hypoxia
• Hypotension
• Corticosteroids
• Sedatives, Analgesics

Mikkelsen et al. AJRCCM 2012 1851307-15 Girard
et al. Crit Care Med 201038 1513-1520 Hopkins
et al. Brain Inj 2010 Sept 21 Epub Hopkins et
al. AJRCCM 1999 16050-56 Hopkins et al. AJRCCM
2005 171340-347 Rothenhausler et al. Gen Hosp
Psychiatry 2001 23 90-96
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Depression

• Prevalence 17-43
• May decrease or stay the same over time ( Hopkins
  2010 Adhikari 2011)
• Risks include alcohol dependence, female
  gender, younger age, cognitive dysfunction,
  hypoglycemia, severity of illness measures, mean
  ICU benzodiazepine dose
• Associated with ability to return to work

Davydow et al. Psychosom Med 2008
70512-9 Adhikari et al. Chest 2009135
678-687 Hopkins et al. Gen Hosp Psychiatry 2010
32 147-55 Dowdy et al. Crit Care Med 2009 37
1702-7 Dowdy et al. Crit Care Med 2008
362726-33 Douglas et al. J Crit Care 2010 25
364 Adhikari et al. Chest 2011 140 1484-93
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Persecutory Delusions/PTSD
Griffiths and Jones BMJ 1999 319427-9.
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Post Traumatic Stress Disorder

• Prevalence 21-35
• Risk factors include benzodiazepine exposure,
  delusional memory, female sex, younger age,
  physical restraint in the ICU, low serum
  cortisol, not receiving corticosteroids, Vent
  days, ICU LOS
• Endogenous personality traits pessimism

Jones et al. Critical Care 2010 14(5)
R168 Myhren et al. Crit Care 2010 14
R14 Davydow Crit Care 2010 14 125 Kapfhammer
et al. Am J Psychiatry 2004 161 45-52 Jones,
Griffiths et al. Crit Care Med 2001 29
573-80 Stoll et al. Int Care Med 1999 25
697-704 Schelling et al. Crit Care Med 1998 26
651-9
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Caregiver Burden
CCM 2008 36 1722-1728
PTSD symptoms consistent with a moderate to major
risk of PTSD were found in 33 of family members.
Azoulay et al. AJRCCM 2005 17 987-994 Jones et
al. Int Care Med 2004 30 456-460
Caregiver depression risk was 34, 31 and 23 at
2, 6, 12 months Lifestyle disruption and
employment reduction were common. Compromised
HRQOL similar to caregivers of stroke/dementia Dep
ressive symptomatology associated with depression
in ARDS survivors
.
Van Pelt et al. AJRCCM 2007 175 167-173 Cameron
et al. Crit Care Med 20063426-33
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• Higher re-experiencing scores on PTSD measures
  were associated with
• higher arousal ratings of negative pictures
  and reduced amygdala, thalamus
• and globus pallidus volumes.
• Chronic re-experiencing of traumatic events may
  result in structural changes
• associated with autonomic arousal and
  acquisition of conditioned fear

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Caregiving as a Risk Factor for Mortality  The
Caregiver Health Effects Study
JAMA. 1999282(23)2215-2219
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• UHN/TRI Lead Canadian Multi-Centre
  Interprofessional Program of Outcomes and
  Rehabilitation in Survivors and Family Caregivers
  after Critical Illness- Program initiated in 2007
• Co-Principal Investigators- Margaret Herridge MD
  MPH and Jill Cameron PhD

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The RECOVER Research Program consists of Four
Phases

• Phase II RECOVER development and pilot testing
• Phase III RECOVER randomized controlled trial
• Phase IV RECOVER KT and Health Policy Change
•  

• Phase I Towards RECOVER

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Patient Outcomes (Quantitative)
FIM Total Score
6MWT ( of predicted)
Total Functional Independence Measure scores at
7-days, 3, 6, and 12-months post ICU discharge
Distance walked in 6 minutes (percent of
predicted values) at 7-days, 3, 6, and 12-months
post ICU discharge
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Patient Outcomes (Quantitative)
SF-36 Physical Component Score
MRC Total Score
SF-36v2 Physical Component Scores at 3-months,
6-months and 12-months post ICU discharge
Total MRC scores at 3-months, 6-months and
12-months post ICU discharge
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Caregiver Outcomes
(Quantitative)
Care-giving Impact Scale
Centre for Epidemiological Studies Depression
Scale
Centre for Epidemiological Studies Depression
(CESD) at 7 day, 3-months, 6-months and
12-months post ICU discharge
Care-giving impact scale at 7 day, 3-months,
6-months and 12-months post ICU discharge
16 considered at risk for symptoms of
depression
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Etiologically Neutral Clinical Phenotypes

• Different clinical phenotypes for outcome and
  possibly muscle and nerve
• correlates for this
• Spectrum determined by age, burden of comorbid
  disease, ICU LOS
• Younger group- more intensive rehab, assist with
  return to work, children
• Middle-aged group with comorbidities- Some rehab,
  OT, planning for new normal
• Older patients- goals of care, disposition,
  complex medical management, OT/social work to
  optimize supports

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Challenges and Opportunities

• There is a spectrum of disability across
  clinical phenotypes both in terms of muscle
  injury/atrophy/dysfunction/ other morbidities and
  also repair and clinical recovery
• We need to understand the basic science
  correlates of muscle, brain and nerve injury
• Different risk groups will require very
  different interventions and these need to be
  constructed and tested
• The family caregiver needs support and is a key
  risk modifier of outcome