ho edit 150721 egdt-promise - jseptic
TRANSCRIPT
HO_edit_150721 EGDT-ProMISe.pptx1
INTRODUCTION
2
INTRODUCTION
Early Goal Directed Therapy
Mar 1997 – Mar 2000 Single center Randomized Controlled Trial 263 enrolled patients
Rivers E et al. N Engl J Med. 2001;345:1368-77. PMID: 11794169.
3
INTRODUCTION
6
4
46.5% 30.5%
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 6
INTRODUCTION
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 7
N Engl J Med. 2015;372:1301-11. PMID: 25776532.
8
METHODS
9
• Prospective randomized controlled trial
• ≥18 years
• • SIRS criteria •
1000mL ! Systolic blood pressure (SBP) ≤90 mmHg ! Mean atrial pressure (MAP) ≤ 65 mmHg
• Lactate ≥4.0 mmol/L 11
,
resuscitation practice
STUDY INTERVENTION
PRIMARY OUTCOMES • 90
•6-72SOFA score •EQ-5D (European Quality of Life – 5 Dimension) • •
•QALY (Quality-Adjusted Life-Years)
• –28, , 1
• –, ICU,
SECONDARY AND TERTIARY OUTCOME
• α: 0.05 (), 1-ß: 80%
• EGDT8%20%
Primary outcome • Fisher’s exact test, Relative Risk, Absolute Risk
Secondary analysis of primary endpoint • MEDS scoreOdds ratio • Sensitivity analysis for missing data • Adherence-adjusted analysis
: Stata/SE ver. 13.0 15
MEDS score: Mortality in Emergency Department Sepsis score
QALYs EQ-5D
• Quality-Adjusted Life-Years: QALYs
– 90QOL – 0 (death) - 1(perfect), negative(worst possible health state) • European Quality of Life – 5 Dimension: EQ-5D – Mobility, self-care, usual activities, pain/discomfort, anxiety/depression –
1:no problem, 2:slight problem, 3:moderate problems, 4:severe problems, 5:extreme problems
http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/qaly.pdf http://www.euroqol.org/about-eq-5d/valuation-of-eq-5d/eq-5d-5l-value-sets.html
Health state value Health state value 11111 1.000 33333 0.516 11231 0.767 42342 0.306 11423 0.606 44444 0.036 22222 0.592 55555 -0.594
Ex)
16
PATIENTS Entry 6192 2415
–841 aggressive care unsuitable –794 do not resuscitation order 2517
↓ Enrolled patient 1260 EGDT: 630, Usual care: 630
↓ EGDT: 625, Usual care: 629
↓≥90 days EGDT: 623, Usual care: 620
↓ EGDT: 356, Usual care: 354
18
CHARACTERISTICS
19
CHARACTERISTICS
SOFA 4.2±2.4 4.3±2.4
Age - yr 66.4±14.6 64.3±15.5
Hypotension - mmHg
20
5.2±3.5 [608]
5.1±3.5 [613]
[ ]: the number of pa.ents with this variable recorded. Baseline physiology values were based on the last recorded value prior to randomiza.on. 21
Site of Infection
Site of infection
EGDT Usual care
Lungs 36.5% 33.1%
23
(hours, IQR) 1.5 (0.4 - 3.1) 1.3 (0.4 - 2.9) 0.34
ICU (days, IQR) 2.6 (1.0 – 5.8) 2.2 (0.0 – 5.3) 0.005
Hospital (days, IQR) 9 (4 - 21) 9 (4 - 18) 0.46
Stay
EGDTICU
Organ Supports (vasopressor, dobutamine)
EGDTVasopressor, DOB
Base line 0-6 hours 6-72 hours EGDT Usual care EGDT Usual care
Vasopressor 2.4% 3.4% 53.3% 46.6% 57.9% 52.6%
Dobutamine 0.3% 0.0% 18.1% 3.8% 17.7% 6.5%
24
EGDT Usual care EGDT Usual care EGDT Usual care
SOFA 6.4 ±3.8
Cardiovascular dysfunction 65.6% 69.2% 76.3% 61.3% 63.2% 59.9%
25
Cardiovascular dysfunction: MAP less than 70 mmHg (irrespective of vasopressor use)
Organ Supports Mechanical Ventilation, Renal Replacement Therapy,
advanced cardiovascular support
(up to 28days) 19.6±12.1hr 19.8±12.1hr 0.78
Renal Replacement Therapy
Days free (up to 28days) 20.6±12.1hr 20.6±11.9hr 0.97
Advanced cardiovascular support (IABP, pace maker…)
No (%) 37.0 30.9 0.026
Days free (up to 28days) 19.6±12.1 19.8±12.0 0.63
13-4
Fluid
0-6 hours 6-72 hours EGDT Usual care EGDT Usual care
Total, mL 2226 ±1443
72
Usual care
Red Cell Infusion
Volume (mL) 426 ±209
Time from randomization to insertion Median, hours (IQR)
EGDT Usual care EGDT Usual care
Arterial catheter 74.2% 62.2% 1.1hr(0.4, 1.9) 1.0hr(0.2, 1.9)
CV catheter 92.1% 50.9% 1.1hr(0.8, 1.5) 1.0hr(0.6, 2.9)
ScvO2 CV catheter 87.3% 0.3%
EGDT10%. Usual careCVC , CVC
28
Physiological and laboratory variables 0-6 hr 6-24 hr 48-72 hr
EGDT Usual care EGDT Usual care EGDT Usual care
Lowest MAP – mm Hg 64.7±11.5 65.0±14.3 64.0±11.1 64.3±11.9 68.9±11.6 68.5±13.7
Lowest SBP – mm Hg 92.2±19.3 91.4±19.9 97.1±19.1 97.9±20.3 107.3±19.5 107.9±18.3
Hemoglobin – g/dL 11.0±2.0 11.3±2.3 11.0±1.8 11.3±2.3 10.7±1.7 10.7±1.8
Cost-effectiveness
Costs (90 days) £ 12,414±14,970 £ 11,424±15,727 0.26
$ 17,647±21,280 $ 16,239±22,356
29
QOL
90QOL 31
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 32
Intensive Care Med. 2015. PMID: 25952825.
ProCESS vs. ARISE vs. ProMISe vs. Rivers* vs. Jones**
*Rivers E et al. N Engl J Med. 2001;345:1368-77. **Jones et al. JAMA. 2010;303:739-46.
33
CHARACTERISTICS
2.8hr (2.1-3.9)
2.7hr (2.0-3.9)
2.8hr (2.1-3.9)
2.7hr (2.0-3.9)
2.5hr (1.8–3.5)
2.5hr (1.8–3.5)
APACHE II 20.8±8.1 20.7±7.5 15.4±6.5 15.8±6.5 18.7±7.1 18.0±7.1
Lactate - mmol/L 4.8±3.1 4.9±3.1 4.2 ±2.8 4.4 ±3.3 5.2±3.5 5.1±3.5
Rivers Jones
Lactate - mmol/L 7.7±4.7 6.9±4.5 4.2±3.1 3.9±3.1
34
Favours control
31.9% 33.7% 18.6% 18.8% 29.5% 29.2%
Rivers (60 days) Jones (hospital)
EGDT Control EGDT Control
44.3% 56.9% 22.7% 16.7%
ProCESS 91.3 85.8 5.1 ±6.3
4.9 ±6.5
11.1 ±10
11.8 ±11.5
4.8 ±5.9
14.1 ±17.3
15.1 ±34.2
6.4 ±9.8
17.6 ±23.0
16.5 24.0
Rivers NA NA NA NA 13.2±13.8 13.0±13.7
Jones 100 100 5.6±7.4 5.9±8.5 12.1±11.7 11.4±10.9
36
Base Line - mL
Jones EGDT Control
37
0
2000
4000
6000
8000
10000
12000
14000
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Rivers Jones ARISE ProCESS ProMISe
10602 8625
12400 11800
6-72 hours
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Rivers Jones ARISE ProCESS ProMISe
4981
Rivers et al. (2001)
Rivers Jones EGDT 27.4% 75.3%
Control 30.3% 72.0%
,CV
EGDT Usual care EGDT Usual care EGDT Usual care
Arterial catheter 91.4% 76.3% 74.2% 62.2% CV catheter 93.6% 57.9% 13.7% 61.9% 92.1% 50.9% ScvO2 CV catheter 93.2% 3.5% 90.0% 0.4% 87.3% 0.3%
Physiological and laboratory variables
ProCESS ARISE ProMISe Rivers Jones EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Pneumonia- % 31.9 33.1 36.5 32.8 36.5 33.1 38.5 39.5 36 32 Urology- % 22.8 20.6 18.7 20.1 17.3 18.7 25.6 27.7 26 27
Abdominal- % 15.7 11.2 8.0 7.6 6.4 8.1 3.4 4.2 16 23
ProCESS ARISE ProMISe Rivers Jones
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
MV, % 38.0 34.4 30.1 31.5 28.9 28.5 55.4 70.7 46.0 50.0
RRT, % 3.1 4.4 13.4 13.6 14.2 13.2 NA NA NA NA
Pneumonia > Urology > Abdominal 41
42
Heuristic , Wikipedia
A heuristic is a simple decision strategy that ignores part of the available information and focuses on the few relevant predictors. Dialogues Clin Neurosci. 2012 Mar;14(1):77-89.
44
() .,
201515ICU
EGDT Single center cohort study, University of Pennsylvania ED (2005 – 2007) EGDT initiated (n=198) vs. EGDT not initiated (n=142)
EGDT(,,)
45 Mikkelsen ME, et al. Chest. 2010 Sep;138(3):551-8.PMID: 20173053
EGDT
Sites and Usual Care
. ,,
ANZ(Finland, Hong Kong, Republic of Ireland) 5131 (Australia 22, New Zealand 3, Finland 2, Hong kong 3, Republic of Ireland 1)
ProMISe U.K, , 56 Teaching hospital 29%, Non-teaching Hospital 71%
U.K
→ (usual care)
• RCT
• RCT
Russell JA, Møller MH, Annane D. Intensive Care Med. 2015 May 22.
[Epub ahead] PMID: 26077056
Protocolised Resuscitation In Sepsis individual patient data Meta-analysis [PRISM] ClinicalTrials.gov NCT02030158
ProCESS, ARISE, ProMISe • Site factors; , , ,
• Patient factors; , , , • Care delivery factors; fluid volume,
48
49
MEDS score
INTRODUCTION
2
INTRODUCTION
Early Goal Directed Therapy
Mar 1997 – Mar 2000 Single center Randomized Controlled Trial 263 enrolled patients
Rivers E et al. N Engl J Med. 2001;345:1368-77. PMID: 11794169.
3
INTRODUCTION
6
4
46.5% 30.5%
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 6
INTRODUCTION
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 7
N Engl J Med. 2015;372:1301-11. PMID: 25776532.
8
METHODS
9
• Prospective randomized controlled trial
• ≥18 years
• • SIRS criteria •
1000mL ! Systolic blood pressure (SBP) ≤90 mmHg ! Mean atrial pressure (MAP) ≤ 65 mmHg
• Lactate ≥4.0 mmol/L 11
,
resuscitation practice
STUDY INTERVENTION
PRIMARY OUTCOMES • 90
•6-72SOFA score •EQ-5D (European Quality of Life – 5 Dimension) • •
•QALY (Quality-Adjusted Life-Years)
• –28, , 1
• –, ICU,
SECONDARY AND TERTIARY OUTCOME
• α: 0.05 (), 1-ß: 80%
• EGDT8%20%
Primary outcome • Fisher’s exact test, Relative Risk, Absolute Risk
Secondary analysis of primary endpoint • MEDS scoreOdds ratio • Sensitivity analysis for missing data • Adherence-adjusted analysis
: Stata/SE ver. 13.0 15
MEDS score: Mortality in Emergency Department Sepsis score
QALYs EQ-5D
• Quality-Adjusted Life-Years: QALYs
– 90QOL – 0 (death) - 1(perfect), negative(worst possible health state) • European Quality of Life – 5 Dimension: EQ-5D – Mobility, self-care, usual activities, pain/discomfort, anxiety/depression –
1:no problem, 2:slight problem, 3:moderate problems, 4:severe problems, 5:extreme problems
http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/qaly.pdf http://www.euroqol.org/about-eq-5d/valuation-of-eq-5d/eq-5d-5l-value-sets.html
Health state value Health state value 11111 1.000 33333 0.516 11231 0.767 42342 0.306 11423 0.606 44444 0.036 22222 0.592 55555 -0.594
Ex)
16
PATIENTS Entry 6192 2415
–841 aggressive care unsuitable –794 do not resuscitation order 2517
↓ Enrolled patient 1260 EGDT: 630, Usual care: 630
↓ EGDT: 625, Usual care: 629
↓≥90 days EGDT: 623, Usual care: 620
↓ EGDT: 356, Usual care: 354
18
CHARACTERISTICS
19
CHARACTERISTICS
SOFA 4.2±2.4 4.3±2.4
Age - yr 66.4±14.6 64.3±15.5
Hypotension - mmHg
20
5.2±3.5 [608]
5.1±3.5 [613]
[ ]: the number of pa.ents with this variable recorded. Baseline physiology values were based on the last recorded value prior to randomiza.on. 21
Site of Infection
Site of infection
EGDT Usual care
Lungs 36.5% 33.1%
23
(hours, IQR) 1.5 (0.4 - 3.1) 1.3 (0.4 - 2.9) 0.34
ICU (days, IQR) 2.6 (1.0 – 5.8) 2.2 (0.0 – 5.3) 0.005
Hospital (days, IQR) 9 (4 - 21) 9 (4 - 18) 0.46
Stay
EGDTICU
Organ Supports (vasopressor, dobutamine)
EGDTVasopressor, DOB
Base line 0-6 hours 6-72 hours EGDT Usual care EGDT Usual care
Vasopressor 2.4% 3.4% 53.3% 46.6% 57.9% 52.6%
Dobutamine 0.3% 0.0% 18.1% 3.8% 17.7% 6.5%
24
EGDT Usual care EGDT Usual care EGDT Usual care
SOFA 6.4 ±3.8
Cardiovascular dysfunction 65.6% 69.2% 76.3% 61.3% 63.2% 59.9%
25
Cardiovascular dysfunction: MAP less than 70 mmHg (irrespective of vasopressor use)
Organ Supports Mechanical Ventilation, Renal Replacement Therapy,
advanced cardiovascular support
(up to 28days) 19.6±12.1hr 19.8±12.1hr 0.78
Renal Replacement Therapy
Days free (up to 28days) 20.6±12.1hr 20.6±11.9hr 0.97
Advanced cardiovascular support (IABP, pace maker…)
No (%) 37.0 30.9 0.026
Days free (up to 28days) 19.6±12.1 19.8±12.0 0.63
13-4
Fluid
0-6 hours 6-72 hours EGDT Usual care EGDT Usual care
Total, mL 2226 ±1443
72
Usual care
Red Cell Infusion
Volume (mL) 426 ±209
Time from randomization to insertion Median, hours (IQR)
EGDT Usual care EGDT Usual care
Arterial catheter 74.2% 62.2% 1.1hr(0.4, 1.9) 1.0hr(0.2, 1.9)
CV catheter 92.1% 50.9% 1.1hr(0.8, 1.5) 1.0hr(0.6, 2.9)
ScvO2 CV catheter 87.3% 0.3%
EGDT10%. Usual careCVC , CVC
28
Physiological and laboratory variables 0-6 hr 6-24 hr 48-72 hr
EGDT Usual care EGDT Usual care EGDT Usual care
Lowest MAP – mm Hg 64.7±11.5 65.0±14.3 64.0±11.1 64.3±11.9 68.9±11.6 68.5±13.7
Lowest SBP – mm Hg 92.2±19.3 91.4±19.9 97.1±19.1 97.9±20.3 107.3±19.5 107.9±18.3
Hemoglobin – g/dL 11.0±2.0 11.3±2.3 11.0±1.8 11.3±2.3 10.7±1.7 10.7±1.8
Cost-effectiveness
Costs (90 days) £ 12,414±14,970 £ 11,424±15,727 0.26
$ 17,647±21,280 $ 16,239±22,356
29
QOL
90QOL 31
ProCESS Protocolized Care for Early Septic Shock (United States, U.S.)
ARISE Australasian Resuscitation In Sepsis Evaluation (Australia and New Zealand, ANZ)
ProMISe Protocolised Management In Sepsis (United Kingdom, U.K) 32
Intensive Care Med. 2015. PMID: 25952825.
ProCESS vs. ARISE vs. ProMISe vs. Rivers* vs. Jones**
*Rivers E et al. N Engl J Med. 2001;345:1368-77. **Jones et al. JAMA. 2010;303:739-46.
33
CHARACTERISTICS
2.8hr (2.1-3.9)
2.7hr (2.0-3.9)
2.8hr (2.1-3.9)
2.7hr (2.0-3.9)
2.5hr (1.8–3.5)
2.5hr (1.8–3.5)
APACHE II 20.8±8.1 20.7±7.5 15.4±6.5 15.8±6.5 18.7±7.1 18.0±7.1
Lactate - mmol/L 4.8±3.1 4.9±3.1 4.2 ±2.8 4.4 ±3.3 5.2±3.5 5.1±3.5
Rivers Jones
Lactate - mmol/L 7.7±4.7 6.9±4.5 4.2±3.1 3.9±3.1
34
Favours control
31.9% 33.7% 18.6% 18.8% 29.5% 29.2%
Rivers (60 days) Jones (hospital)
EGDT Control EGDT Control
44.3% 56.9% 22.7% 16.7%
ProCESS 91.3 85.8 5.1 ±6.3
4.9 ±6.5
11.1 ±10
11.8 ±11.5
4.8 ±5.9
14.1 ±17.3
15.1 ±34.2
6.4 ±9.8
17.6 ±23.0
16.5 24.0
Rivers NA NA NA NA 13.2±13.8 13.0±13.7
Jones 100 100 5.6±7.4 5.9±8.5 12.1±11.7 11.4±10.9
36
Base Line - mL
Jones EGDT Control
37
0
2000
4000
6000
8000
10000
12000
14000
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Rivers Jones ARISE ProCESS ProMISe
10602 8625
12400 11800
6-72 hours
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Rivers Jones ARISE ProCESS ProMISe
4981
Rivers et al. (2001)
Rivers Jones EGDT 27.4% 75.3%
Control 30.3% 72.0%
,CV
EGDT Usual care EGDT Usual care EGDT Usual care
Arterial catheter 91.4% 76.3% 74.2% 62.2% CV catheter 93.6% 57.9% 13.7% 61.9% 92.1% 50.9% ScvO2 CV catheter 93.2% 3.5% 90.0% 0.4% 87.3% 0.3%
Physiological and laboratory variables
ProCESS ARISE ProMISe Rivers Jones EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
Pneumonia- % 31.9 33.1 36.5 32.8 36.5 33.1 38.5 39.5 36 32 Urology- % 22.8 20.6 18.7 20.1 17.3 18.7 25.6 27.7 26 27
Abdominal- % 15.7 11.2 8.0 7.6 6.4 8.1 3.4 4.2 16 23
ProCESS ARISE ProMISe Rivers Jones
EGDT Control EGDT Control EGDT Control EGDT Control EGDT Control
MV, % 38.0 34.4 30.1 31.5 28.9 28.5 55.4 70.7 46.0 50.0
RRT, % 3.1 4.4 13.4 13.6 14.2 13.2 NA NA NA NA
Pneumonia > Urology > Abdominal 41
42
Heuristic , Wikipedia
A heuristic is a simple decision strategy that ignores part of the available information and focuses on the few relevant predictors. Dialogues Clin Neurosci. 2012 Mar;14(1):77-89.
44
() .,
201515ICU
EGDT Single center cohort study, University of Pennsylvania ED (2005 – 2007) EGDT initiated (n=198) vs. EGDT not initiated (n=142)
EGDT(,,)
45 Mikkelsen ME, et al. Chest. 2010 Sep;138(3):551-8.PMID: 20173053
EGDT
Sites and Usual Care
. ,,
ANZ(Finland, Hong Kong, Republic of Ireland) 5131 (Australia 22, New Zealand 3, Finland 2, Hong kong 3, Republic of Ireland 1)
ProMISe U.K, , 56 Teaching hospital 29%, Non-teaching Hospital 71%
U.K
→ (usual care)
• RCT
• RCT
Russell JA, Møller MH, Annane D. Intensive Care Med. 2015 May 22.
[Epub ahead] PMID: 26077056
Protocolised Resuscitation In Sepsis individual patient data Meta-analysis [PRISM] ClinicalTrials.gov NCT02030158
ProCESS, ARISE, ProMISe • Site factors; , , ,
• Patient factors; , , , • Care delivery factors; fluid volume,
48
49
MEDS score