Impact of Frailty in Critically Ill Patients: Does It Add Any Value?

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Impact of Frailty in Critically Ill Patients: Does It Add Any Value? Sean M Bagshaw, MD, MSc Department of Critical Care Medicine, University of Alberta, Edmonton, Canada 2nd Inter-Congress Conference of the Polish Society of Anaesthesiology and Intensive Therapy, Karpacz, Poland November 25th, 2016 17:55-18:15

2016 Disclosures Salary support: Canada government Grant support: Canada/Alberta government Speaking honoraria/travel: academic institutions Speaking/consulting: Baxter Healthcare Corp. Steering Committee: Spectral Medical Inc. Data Safety Monitoring Committee: LJPC I am not a geriatrician nor necessarily an expert in frailty

Objectives 1. Define and review the biologic concept of frailty 2. Understand the tools to capture frailty and identify a vulnerable population 3. Understand the impact of frailty on outcomes after acute stress and critical illness

FRAILTY is a multi-dimensional syndrome or state related to ageing first described in elderly patients Characterized by: Loss of reserve (energy, physical, cognitive, health) and the accumulation of deficits (individually reversible but collectively insurmountable) Consequence: Heightened vulnerability or state-at-risk to adverse outcomes

Punished inefficiency Excess + prolonged response: IL-6, IL-10, TNF, CRP, CXCL-10 Impaired GH (IGFs), sex hormones, DHES + cortisol stem cells, T-cell production, B-cell Ab response, phagocytic activity Implications for ICU settings: Response the therapy Vulnerability to complications Death Recovery disability, impaired function, loss of autonomy Singer J et al AATS 2016

Patterns of Functional Decline at End of Life Sudden Death Terminal Illness Organ Failure Frailty Definitions: Sudden death = cardiac arrest or trauma; Terminal illness = cancer; Organ failure = HF/COPD; Frailty: residence in nursing home Lunney JR et al JAMA 2003

Distribution of Disability Trajectories in the Last Year of Life, According to Condition Leading to Death among the 383 Decedents n=383 elderly decedents FRAILTY ~ most common condition leading to death Gill TM et al. N Engl J Med 2010;362:1173-1180

Cumulative Deficit Model CSHA captured 92 variables such as symptoms, signs, laboratory values, disease states and disabilities collectively termed deficits Frailty Index (FI) = # deficits / total variables Frailty represents the cumulative effects of individual deficits Reinforces the concept of physiologic/homeostatic reserve and biological gradation FI strongly correlates with risk of death and institutionalization Jones et al J Am Ger Soc 2004

Physical Phenotype Model Frailty Characteristics Shrinking, weight loss (unintentional), sarcopenia Weakness Poor endurance, exhaustion, slowness Low activity CHS Measure >10 lb lost unintentionally in prior 1 year Grip strength: lowest 20% (by sex, BMI) exhaustion (self-reported); walking time/15 ft: slowest 20% (by sex, height) Kcal/week: lowest 20% (males <383 Kcal/wk; females <270 Kcal/wk) 1. Shrinking: weight loss, unintentional, of 10 lbs in prior year) 2. Weakness: grip strength in lowest 20% at baseline (age/bmi) 3. Poor endurance/energy: self report of exhaustion (CES-D scale) 4. Slowness: slowest 20% at baseline for time to walk 15 ft (sex/height) 5. Low physical activity: lowest quintile of physical activity (gender) Frail 3 Vulnerable 1-2 Not Frail 0 Fried et al (Cardiovascular Health Study)_J Gerontol Biol Sci Med Sci 2001

Domains to Define, Measure and Operationalize Domain General Health Status Physical Function Cognitive Function Mobility Strength Energy Nutritional Status Skeletal Muscle Mass Mood Social relations/support Laboratory Markers Operational Measures Hospitalizations, global assessment of functioning scale, self-rated health BADL, IADL, functional independence measure (FIM) MMSE, Montreal Cognitive assessment, clock drawing test Short physical performance battery, gait speed, TGUG, chair rise, mobility aid Grip strength, stair climb, subjective assessment of weakness Fatigue severity scale, subjective assessment of exhaustion or fatigue BMI, weight, albumin/prealbumin, mini-nutritional assessment, weight loss Anthropometry, bioelectrical impedance, MRI/CT/ultrasound Geriatric depression scale, HADS, self-reported depression/anxiety Availability of social resources, subjective assessment of loneliness or isolation Inflammatory mediators (IL-6, IL-1, TNF, CRP), oxidized LDL, creatinine Rajabali et al Can J Cardiol 2016; De Vries et al Ageing Research Reviews 2011

Methods to Screen and Diagnose Frailty Method Description Items Example Evaluated in ICU Frailty Index (FI) Deficit accumulation 30-70 CSHA FI (70 items) YES Physical phenotype 3 physical features 3-5 Fried (CHS) criteria YES Physical performance measures Judgement-Based tools Multidimensional tools Sarcopenia Single measure 1 Global subjective assessment Battery of assessments across domains Imaging to assess skeletal muscle Gait speed, grip strength, chair stand NO 1 Clinical Frailty Scale YES 5-20 1 EFS, FRAIL, CAF, Groningen Frailty Indicator CT scan psoas or rectus femoris Gold Standard: Comprehensive Geriatric Assessment (CGA) NO YES Rajabali et al Can J Cardiol 2016

Single geriatric ICU in China (mean age 82 yr) Novel FI based on 52 variables (23 chronic + 31 acute) All patients who died had FI > 0.46 All patients who survived 30-days had FI <0.22 Each 1% in FI associated with 11% in 30-day mortality (OR 1.11; 95% CI, 1.07-1.15) n=155 Zeng et al J Genrontol A Biol Sci Med Sci 2015

n=594 Non-Frail (58.2%) Intermediate (31.3%) Frail* (10.4%) Age (yr) 71 (67-94) 75 (65-92) 76 (65-94) Female Sex (%) 67.6 52.7 41.9 Post-operative complications 1.0 2.06 (1.2-3.6) 2.54 (1.1-5.8) Length of stay 1.0 1.49 (1.2-1.8) 1.69 (1.3-2.2) Institutionalized 1.0 3.2 (1.0-9.9) 20.5 (5.5-76) * FRAILTY defined by the physical phenotype criteria proposed by Fried Makary et al JACS 2010

n=196 Le Maguet et al ICM 2014

CFS score and mathematically derived FI highly correlated (Pearson 0.80, p<0.01) Available at: http://geriatricresearch.medicine.dal.ca/clinical_frailty_scale.htm Rockwood et al CMAJ 2005

Survival Institutionalization For each 1-category in CFS score ~ 21.2% death and 23.9% institutionalization Rockwood et al CMAJ 2005

Frailty The What and When Rapid Case Finding CFS FI (efi) Gait Speed Define Frailty Components Multidimensional assessment (i.e. EFS) Address Components Informed decisionmaking ICU admission Identify Contributors Precision Recovery Adapted from D. Rolfson

Frequency (%) 35 30 25 32 Frailty (CFS > 4) ~ 32.8% (95% CI, 28.3-37.5) 20 15 10 5 0 20 11 12 12 6 4 2 1 2 3 4 5 6 7 8 Clinical Frailty Scale (CFS) score Bagshaw et al CMAJ 2014

vulnerability risk for death time for recovery functional impairment Bagshaw et al CMAJ 2014

Survival 1-year after ICU Admission Bagshaw et al CMAJ 2014

Secondary Analysis of BRAIN/MIND ICU Studies CFS Scores Stratified by Age Mortality Stratified by CFS Score Prevalence of frailty 30% (n=307) (50% age < 65 years) CFS score associated with mortality, disability in IADL and worse physical (not mental) HRQL CFS scores not associated with disability in BADL or cognition n=1040 Brummel Courtesy NE, of et Brummel al. Under N et al Review In Press

But Does It Add Value? 1. Better informed triage decisions ~ Regarding to suitability and likely benefit for ICU support 2. Guide and inform patient-centered decision-making ~ Regarding scope/duration of ICU support (i.e., time-limited trials) Regarding establishing/revisiting goals of care Regarding managing post-icu survivorship expectations and experience (i.e., impact on HRQL, new disability, institutionalization, rehospitalization)

63 critically ill mechanically ventilated patients (age 54.7; APACHE II 23.5) -17.7% Puthucheary et al JAMA 2014

Transition to persistent critical illness At ~ 10 days after ICU admission, acuity did not predict mortality better than antecedent characteristics (age, sex, comorbid disease) (variable transition point by case-mix and acuity) Prevalence only 5.0% but accounted for 32.8% of ICU-bed days and only 46.5% returned home Iwashyna et al Lancet Resp Med 2016

And How Else May It Add Value? 3. Transitions of care ~ Priorities/specialized needs for transition from ICU to ward setting Priorities/specialized needs for hospital to community (i.e., CGA) 4. Interventions (recognizing vulnerability)~ Focused on maximizing physical recovery (i.e., minimizing avoidable disability) Focused on cognitive, psycho-social, and emotional recovery Focused on care-giver burden/experience Focused strategy towards palliation

Frailty An Integrated Model Rapid Case Finding CFS Gait Speed FI (efi) Define Frailty Components Multidimensional assessment (i.e. EFS) Address Components Informed decisionmaking ICU admission ICU Transition Community Transition

Summary Frailty is a multi-dimensional syndrome contributing to vulnerability to adverse events: can be measured in critically ill patients is associated with risk adverse events, death, re-hospitalization is associated with HRQL, new disability and functional dependence identifies a vulnerable population Frailty Assessment at ICU admission should focus on case-finding for near-term prognostication, guiding clinical care and decision-making and after ICU should start to focus more comprehensive assessments, care transitions and specialist referral

Thank Acknowledgements: You For Your Attention Investigators: Tom Stelfox, Rob McDermid, Sumit Majumdar, Daryl Rolfson, Daniel Stollery, Ella Rokosh, Ross Tsuyuki, Quazi Ibrahim, Dan Zuege, David Zygun, Darren Hudson Coordinators: Tracy Davyduke, Maliha Muneer, Nadia Baig, Barbara Artiuch, Kristen Reid, Gwen Thompson, Robin Scheelar, Jennifer Barchard, Dawn Opgenorth Questions? bagshaw@ualberta.ca