Supplementary Appendix 1
Contents
Acknowledgements....................................................................................................................................... 2
Supplementary Methods .............................................................................................................................. 3
Figures ........................................................................................................................................................... 4
eFigure 1a - Patient Flow Diagram (Chart abstraction and patient recruitment .................................. 5
eFigure 1b - Longitudinal Cohort Patient Flow Diagram (Patient follow up)........................................ 6
eFigure 2 - Physical Function Among Survivors. ................................................................................... 7
eFigure 3 - Combined Outcome of Mortality and Change of Physical Function from Baseline at
Different Time Points in the Longitudinal Cohort by Baseline Physical Function ................................. 9
Tables .......................................................................................................................................................... 10
eTable 1 - Items Included in the Frailty Index ..................................................................................... 11
eTable2a - Logistic Regression Models Predicting Survival at 12 Months After ICU Admission. ....... 12
eTable 3a - Linear Regression Model Predicting 12-month SF-36 Physical Function Scores Among
Survivors.............................................................................................................................................. 13
References .................................................................................................................................................. 14
Acknowledgements
We would like to thank Jennifer Korol and other staff at the Clinical Evaluation Research Unit at the
Kingston General Hospital for their role in coordinating the study. We would also like to thank the
following colleagues who participated in data collection for this study (number in brackets refers to
number of patients enrolled at each site):
Hôpital du Sacré-Coeur de Montréal (71), Montréal, Québec: Martin Albert, Patrice Deroy, Caroline
Chagnon, Huber Simard.
Hôpital de L’Enfant-Jésus (50), Québec City, Québec: Alexis Turgeon, Chantal Gagné, Marie Thibodeau,
Suzy Lavoie, Michèle D’Amours
Hôpital Laval (50), Québec City, Québec: Francois Lellouche, Marie-Claude Ferland, Patrick Dussault.
Royal University Hospital (49), Saskatoon, Saskatchewan: John Reid, Rose Rumanski, Susan Hattori
University of Alberta Hospital (48), Edmonton, Alberta : Sean Bagshaw; Karen O’Hara Banack; Nadia
Baig; Sheri Cholin, Samantha Taylor
St. Paul’s Hospital (46), Vancouver, British Columbia: Peter Dodek, Betty Jean Ashley.
Kingston General Hospital (39), Kingston, Ontario: John Muscedere, Susan Fleury, Nicole O’Callaghan.
Ottawa Hospital, Civic Campus (32), Ottawa, Ontario: Richard Hodder, Mary Jo Lewis, Erin Murphy,
Tracy McCardle
Royal Alexandra Hospital (31), Edmonton, Alberta: Jim Kutsogiannis, Patrica Thompson, Kirby Scott,
Reagan Bartel, Darlene Jossy
Foothills Hospital (29), Calgary, Alberta: Tom Stelfox, Stephanie Todd, Crystal Wilson, Jamie Boyd
St. Boniface Hospital Winnipeg (29), Winnipeg, Manitoba: Allan Garland, Kim Wiebe, Nicole Martens,
Wellam Yu Ko
Hôpital Maisonneuve-Rosemont (24), Montréal, Québec: Stéphane Ahern, Johanne Harvey, Brigitte
Beauregard
Mount Sinai Hospital (19), Toronto, Ontario: Sangeeta Mehta, Maedean Brown, Scott Kim, Alex Day.
Royal Columbian (17), New Westminster, BC: Sean Keenan, Miroslav Svetik, Jacquie Stevenson
Sunnybrook Health Sciences Centre (17), Toronto, Ontario: Rob Fowler, Nicole Marinoff, Derek
Parsotam, Ashwati Raghunath
St. Michael’s Hospital MSICU/NTICU (14/0), Toronto, Ontario: Karen Burns, Orla Smith, Yoon Lee, Kerri
Porretta, Julia Lee, Marlene Santos
Peter Lougheed Hospital (11), Calgary, Alberta: Tom Stelfox, Cheryl Dielissen, Stephanie Todd
Toronto General Hospital (11), Toronto, Ontario: Neil Lazar; Paulina Farias, Andrea Matte, Emily Stern
St. Joseph’s Healthcare (11), Hamilton, Ontario: Deborah Cook, Ellen McDonald, France Clarke, Nicole
Zytaruk, Christina Maria Katsios
Victoria General Hospital (5), Victoria, British Columbia: Gordon Wood, Fiona Auld, Leslie Atkins, Peggy
Leonard
Royal Jubilee Hospital (5), Victoria, British Columbia: Gordon Wood, Fiona Auld, Leslie Atkins, Peggy
Leonard
Winnipeg Health Sciences Centre (2), Winnipeg, Manitoba: Allan Garland, Wendy Janz, Mandi Siddiqui.
Supplementary Methods
From proxy responses to the comprehensive geriatric assessment, we calculated the Frailty Index. The
Frailty Index identified 43 deficits at baseline (Appendix eTable 1), each coded as 0 (absent), 1 (present),
or 0·5 (where intermediate values were possible).1 The score was calculated as the cumulative
proportion of deficits present (minimum score 0; maximum score 1·0). The score was considered a
continuous variable for modeling but was then graded as fit (> 0 and ≤ 0·2), mild frailty (> 0·2 and < 0·4)
or moderate/severe frailty (≥ 0·4) for descriptive purposes.2 At baseline, we also recorded patients’
baseline physical function (see Short Form-36 (SF-36) details below), and the Informant Questionnaire
on Cognitive Decline in the Elderly (IQCODE) using proxy responses from family members. The IQCODE,
an unweighted average of 16 items, identifies changes in patients’ cognitive performance; this
instrument has high reliability and good validity.3-5 A score > 3 indicates that some cognitive decline has
occurred.3
In both the hospital and longitudinal cohorts, variables collected from hospital records at the time of ICU
admission were age, sex, admission diagnosis, admission type (medical vs. surgical), Acute Physiology
and Chronic Health Evaluation (APACHE) II score6, Functional Comorbidity Index7, and Charlson
Comorbidity Index.8 We also measured multiple organ dysfunction using sequential organ failure
assessment (SOFA) scores at admission and daily in ICU.9 All patients were followed prospectively to
document duration of mechanical ventilation, and ICU and hospital lengths of stay.
Figures
4
eFigure 1a - Patient Flow Diagram (Chart abstraction and patient recruitment)
All consecutive patients > 80 years old were assessed for eligibility (n = 3064)
Patient already in longitudinal
cohort (n=610)
Site already met chart
abstraction quota (n=1393)
Not eligible for follow-up (n=1405)
614 ICU stay< 24 hours
420 Family caregiver did not visit the patient within
96 hours of ICU admission
258 Patient acutely dying
86 Family caregiver does not speak English or French
17 Family caregiver is paid to provide care
8 Patient is not a resident of Canada
2 Family caregiver < 18 yrs old
Eligible for follow-up (n=1659)
Consecutive hospital chart abstractions
(n=1061)
Patient in ICU<24 hours
(n=167)
Hospital only cohort (n=894)
Eligible but excluded from follow-up
(n=1049)
474 Missed the caregiver
464 Caregiver refused consent
44 Family dynamics precluded consent
67 Other
Longitudinal cohort (n =610)
5
eFigure 1b - Longitudinal Cohort Patient Flow Diagram (Patient follow up)
Longitudinal cohort
(n =610)
Death or drop out in hospital (n=164)
85 died in ICU
73 died in hospital after ICU discharge
6 withdrew consent
Any quarterly follow-up data (n =446)
3-month follow-up*
322-Completed follow-up
198-Died
90-Missing
6-month follow-up*
281-Completed follow-up
228-Died
101-Missing
9-month follow-up*
241-Completed follow-up
243-Died
126-Missing
12-month follow up*
254-Completed follow-up
253-Died
103-Missing
**Patients with known primary
outcome at one year
(n =505)
Legend:
ICU-Intensive Care Unit.
*89% reported by family members at month 3; 88% reported by family members at month 6;
87% reported by family members at month 9 and 87% reported by family members at month 12.
** Two patients with 12 month follow-up could not be evaluated for PF recovery due to a missing baseline value.
6
eFigure 2 - Physical Function Among Survivors.
Panel A: SF-36 Physical Functioning Domain
7
Panel B: SF-36 Physical Component Score
Legend: The average age-sex matched Canadian norms are depicted by the red dotted line. The
differences between values for the patients and Canadian norms are statistically significant (at <0.05
level) at all time points (month 3, 6, 9 and 12) and this applies to both PF and PCS.
8
eFigure 3 - Combined Outcome of Mortality and Change of Physical Function from Baseline at
Different Time Points in the Longitudinal Cohort by Baseline Physical Function
Panel A: Patients with baseline PF<40
Deceased
Alive with PF score<10
Alive with PF>=10 but 10 or more points below baseline
Alive with PF>=10 and not 10 or more points below baseline
n=263
n=278
50
70
90
n=282
0 10
30
Proportion of patients
n=277
3 months
6 months
9 months
12 months
Panel B: Patients with baseline PF≥40
Deceased
Alive with PF score<10
Alive with PF>=10 but 10 or more points below baseline
Alive with PF>=10 and not 10 or more points below baseline
n=217
n=227
30
50
70
90
n=226
0 10
Proportion of patients
n=242
3 months
6 months
9 months
12 months
9
Tables
10
eTable 1 - Items Included in the Frailty Index
#
Items contributed to the FI
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
Overall health of the patient?
Do you think the patient was depressed?
Do you think the patient worried a lot or got anxious?
Do you think the patient felt exhausted or tired all the time?
Did the patient have sleep problems?
Did the patient have problems with memory or thinking?
Did the patient have any problems speaking to make him/herself understood?
Did the patient have difficulty hearing?
Did the patient have problems with eyesight? (even when wearing glasses)
Did the patient having problems with balance?
Did the patient complain of feeling dizzy or lightheaded?
Did the patient need assistance of a person or aid to prevent falling?
Did the patient hold on to furniture to keep from failing?
Was the patient able to walk alone?
Was the patient able to get out of a bed or chair alone?
Did the patient have problems with bowel control?
Did the patient have problems with bladder control?
Did the patient experience any unplanned weight loss in the last 6 months?
What was the patient’s food intake in the week prior to ICU admission?
Was the patient able to carry out some day to day tasks?
Feed himself/herself?
Take a bath or shower?
Dress himself/herself?
Drive?
Look after his/her own medications?
Do day-to-day shopping?
Do day-to-day household cleaning?
Cook well enough to maintain his/her nutrition?
Look after his/her own banking and financial affairs?
Overall health of the patient?
Myocardial infarct
Congestive heart failure
Peripheral vascular disease
Cerebrovascular disease +/- hemiplegia
Dementia
Chronic pulmonary disease
Connective tissue disease
Ulcer disease
Any liver disease
Diabetes
Moderate or several renal diseases
Diabetes with end organ damage
Any tumor
11
eTable2a - Logistic Regression Models Predicting Survival at 12 Months After ICU Admission.
Variables
Age (per 5 years)
Sex (Male vs. Female)
APACHE II score (per 10 points)
Marital status (Married or living as married vs. Other)
Baseline SOFA score (per 5 points)
Admission type (Medical vs. Surgical)
Surgical elective vs. Medical
Surgical emergency vs. Medical
Primary ICU diagnosis
CABG/Valve vs. Cardiovascular/vascular
Gastrointestinal vs. Cardiovascular/vascular
Neurologic vs. Cardiovascular/vascular
Other vs. Cardiovascular/vascular
Respiratory vs. Cardiovascular/vascular
Sepsis vs. Cardiovascular/vascular
Stroke vs. Cardiovascular/vascular
Trauma vs. Cardiovascular/vascular
Baseline PF score (per 50 points)
Charlson Comorbidity Index (per 2 units)
IQCODE at baseline (per 0.5 point)
Frailty Index (per 0.2 point)
Family preferences for life sustaining treatment
Comforts measures vs. other
**Total model degrees of freedom/deaths
*c-statistic
Single Predictor
OR (95% CI)
c*
0.90 (0.74, 1.09)
0.64 (0.49, 0.84)
0.50 (0.38, 0.66)
0.89 (0.70, 1.12)
0.61 (0.48, 0.78)
0.51
0.56
0.63
0.52
0.59
0.61
P-value
0.29
0.002
<0.0001
0.32
<0.0001
<0.0001
0.62
0.61 (0.36, 1.01)
1 to 8/252
0.51 to 0.65
0.94 (0.75, 1.19)
0.63
0.68 (0.47, 0.97)
0.58 (0.42, 0.80)
1.05 (0.77, 1.43)
0.73 (0.47, 1.12)
0.03
0.001
0.74
0.15
0.39
1.35 (0.68, 2.69)
1.29 (0.76, 2.19)
4.12 (2.10, 8.10)
1.68 (1.10, 2.56)
8.75 (3.38, 22.63)
0.83 (0.44, 1.55)
2.20 (0.88, 5.52)
0.93 (0.39, 2.26)
0.83 (0.4, 1.72)
0.64 (0.36, 1.13)
1.10 (0.53, 2.28)
1.40 (0.65, 3.02)
1.55 (1.25, 1.93)
0.59 (0.49, 0.70)
0.85 (0.70, 1.03)
0.47 (0.40, 0.54)
Multivariable Predictor Model
OR (95% CI)
P-value
<0.0001
<0.0001
0.58
0.63
0.56
0.65
<0.0001
<0.0001
0.10
<0.0001
0.54
0.06
7.19 (2.71, 19.10)
0.73 (0.37, 1.42)
1.09 (0.50, 2.40)
1.19 (0.41, 3.41)
0.93 (0.39, 2.24)
0.79 (0.41, 1.52)
0.69 (0.28, 1.68)
1.04 (0.49, 2.24)
0.80 (0.56, 1.16)
0.71 (0.56, 0.91)
1.05 (0.84, 1.32)
0.53 (0.36, 0.78)
0.55 (0.33, 0.93)
20/250
0.76
0.24
0.006
0.65
0.002
0.02
The total sample size ranged from 505 in some single predictor models to 502 in the full models due to 3 patients with some missing covariates.
OR-Odds ratio; CI-Confidence interval; FI-Frailty Index.
The outcome of this model is survival at 12 months. OR>1 indicate favorable association.
Predictors with p≤0.05 are in bold.
12
eTable 3a - Linear Regression Model Predicting 12-month SF-36 Physical Function Scores Among Survivors.
Single Predictor
Estimate (SE)
P-value
Variables
Age (per 5 years)
Sex (Male vs. Female)
APACHE II score (per 10 points)
Marital status (Married or living as married vs. Other)
Baseline SOFA score (per 5 points)
Admission type (Medical vs. Surgical)
-5.8 (1.6)
-0.2 (2.5)
-9.4 (2.3)
6.1 (3.6)
-4.1 (2.4)
Surgical elective
Surgical emergency
Medical
30.5 (7.1)
9.6 (3.7)
Referent
CABG/Valve
Gastrointestinal
Neurologic
Other
Respiratory
Sepsis
Stroke
Trauma
Cardiovascular/vascular
34.9 (5.0)
-2.2 (6.2)
9.8 (9.1)
-8.8 (5.7)
-4.4 (6.0)
-5.0 (6.6)
-13.8 (5.1)
1.7 (7.3)
Referent
21.4 (2.4)
-7.9 (1.1)
-6.5 (1.7)
-19.9 (1.8)
-12.6 (4.8)
Primary ICU diagnosis
0.002
0.93
0.0006
0.10
0.11
0.0002
Multivariable
Estimate (SE)
P-value
-2.0 (1.5)
-4.8 (2.7)
-6.8 (2.6)
4.7 (3.1)
-2.0 (2.6)
8.4 (6.9)
1.8 (3.9)
Referent
<0.0001
Baseline PF score (per 50 points)
Charlson Comorbidity Index (per 2 units)
IQCODE at baseline (per 0.5 point)
Frailty Index (per 0.2 point)
Family preferences for life sustaining treatment Comforts measures vs. Other
0.19
0.09
0.02
0.15
0.46
0.48
<0.0001
<0.0001
0.001
<0.0001
0.02
0.0007
27.6 (5.3)
0.0 (4.8)
-0.2 (8.0)
0.8 (4.3)
-2.7 (6.3)
1.6 (5.6)
-20.3 (4.5)
-2.8 (6.3)
Referent
12.6 (3.2)
-2.6 (1.9)
-0.5 (1.0)
-7.1 (3.3)
-7.5 (3.6)
0.0008
0.17
0.61
0.04
0.05
SE - Standard error
Predictors with p≤0.05 are in bold.
13
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