Professional Documents
Culture Documents
1. Why
Severe Sepsis
Different criteria
yielding different results
SIRS Sensitivity
Severe Sepsis
Confusing
Most people say sepsis when they mean
severe sepsis
Number of cases
Total mortality
250K 375K
Germany 60.5%
Heublein et al, In press
Variable Variables
hypotension (SAP <90, MAP <60 or <70, fall in SAP >40)
AND/OR
.. that persists despite adequate fluid resuscitation (either unspecified
or after challenges of either 20 ml/kg OR 1000 ml)
AND/OR
AND/OR
new onset organ dysfunction (defined variably using APACHE II,
APACHE III, or SOFA cardiovascular component
2. How
Richard Hotchkiss
Greg Martin
Djilalli Annane
Mitchell Levy
Manu Shankar-Hari
Michael Bauer
John Marshall
Chris Seymour
Rinaldo Bellomo
Steve Opal
Gordon Bernard
Gordon Rubenfeld
Jean-Daniel Chiche
Craig Coopersmith
Jean-Louis Vincent
The Document
Singer M, Deutschman CS,
Seymour CW, Shankar-Hari M et al.
3. What
2.
3.
4.
Definitions
Per the Merriam Webster English Dictionary:
Definition
a statement expressing the essential nature of something
or, more generically,
As opposed to the
regulated host response
that characterizes the non-septic response to infection
Treatment ?
NO. Management is the same
Pathobiology ?
Sepsis Definitions
Advantages
Incorporates most up-to-date thinking on sepsis
pathobiology
Provides closest approximation possible to describing
what sepsis is
Concerns
Of limited practical utility as they contain elements that
cannot be clinically identified
organ dysfunction
dysregulated host response
Clinical criteria
Existing
Newly derived and validated
Contributors
Gordon Rubenfeld, MD MSc
Jeremy Kahn, MD MS
Manu Shankar-Hari, MD MS
Vincent Liu, MD MS
Christopher Seymour MD MS
Frank M. Brunkhorst, MD
Clifford Deutschman, MD MS
What is sepsis?
A life threatening organ dysfunction caused by a
dysregulated host response to
infection.
What is sepsis?
A life threatening organ dysfunction caused by a
dysregulated host response to
infection.
What is sepsis?
A life threatening organ dysfunction caused by a
dysregulated host response to
infection.
What is sepsis?
A life threatening organ dysfunction caused by a
dysregulated host response to
infection.
What is sepsis?
Infected
Septic
Really
sick
We did not..
Study criteria for infection
Build an alert or sniffer among non-infected patients
We did..
Infected
Really
sick
Cohort
Denominator (cohort)
Cases
Our challenges
What data to use?
How to identify infection?
What clinical criteria to study?
External datasets
>700,000 encounters
Transfer to ICU
Admission to ED
Time of infection
suspected
72
hrs
6 hrs
Discharge
Septic
Statistic
Total encounters
148,907
Confirmed bacteremia
6,875 (5)
61 (19)
63,311 (43)
128,358 (86)
65,934 (44)
Ward
49354 (33)
Intensive care
15,768 (11)
50
40
40
40
30
30
30
20
20
20
10
10
10
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
35
3 4
9 10 11 12 13 14
16
28
6 7
28
48
2 3
7 8 9 10 11 12 13 14
,7
15 8 9
,0
8
4, 5
42
7, 9
87
4, 8
42
1, 6
60
1, 0
08
8
78
8
44
2
36
6
21
1
12
8
11
8
52
12
2
SOFA score
29
40
27
,
16 56 0
,0
9, 67
6
5, 90
0
3, 13
3
1, 26
9
1, 92
04
7
62
5
41
8
23
8
16
3
11
1
90
72
41
20
31
SIRS criteria
4
1,
77
3
6,
52
2
,8
,3
57
1
22
30
,1
20
No. of
patients
15
These
criteria are complex
Logistic organ dysfunction score
and require laboratory tests
50
50
54
4
36
SOFA score
SIRS criteria
Proportion (%)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
24
5
45
8
62
7
77
8
87
3
86
2
80
3
69
2
58
8
46
7
39
7
31
0
25
1
17
0
13
5
10
2
17
4
4
1,
85
2,
45
2
2,
26
1
99
Proportion (%)
No. of
patients
32
10
55
10
10
86
20
20
77
20
30
68
30
30
92
40
40
69
40
50
37
50
60
50
Assessment of criteria
ICU encounters
N = 7,932
AUROC in-hospital
mortality
SIRS
0.64 (0.62,
0.66)
SOFA
<0.01
0.74 (0.73,
0.76)
LODS
<0.01
0.20
0.75 (0.73,
0.76)
qSOFA
0.01
<0.01
<0.01
0.66 (0.64,
0.68)
SIRS
0.76 (0.75,
0.77)
SOFA
<0.01
0.79 (0.78,
0.80)
LODS
<0.01
<0.01
0.81 (0.80,
0.82)
qSOFA
<0.01
<0.01
0.72
0.81 (0.80,
0.82)
Assessment of criteria
10000
ICU encounters
N = 7,932
1000
100
10
1
0.1
1
0.9
0.6
1.1
1.3
14.0
1.1 Decile
13.3
13.2
14.6
16.1
17.0
of15.1
baseline
14.6
15.6 risk
16.6
15.6
16.5
17.4
mortality
18.8
20.0
of17.9
in-hospital
17.4
18.3
19.2
18.3
19.2
20.9
10
21.9
20.9
26.8
Assessment of criteria
10000
1000
100
10
1
0.1
0.2
0.2
0.6
0.8
0.6
1.0
10
1.4
1.9
2.4
2.9
3.4
3.9
4.6
6.2
5.2
17.7
Decile
risk
in-hospital
1.1 of1.6baseline
2.1
2.6 of 3.1
3.6
4.2
1.6
2.1
2.6
3.1
3.6
4.2
5.2
mortality
Decile of baseline risk for in-hospital mortality
Change in SOFA
Increase by 2 or SOFA points from baseline
Greater predictive validity than SIRS criteria
Serum lactate
Not retained during qSOFA model build
Baseline risk
qSOFA + baseline
qSOFA + lactate 2.0
+ baseline
1 - 1-specificity
Specificity
Sensitivity
Sensitivity
10
0.1
1
1.0
0.6
1.4
10
1.9
2.7
3.4
4.2
5.0
5.8
6.7
7.9
10.4
8.9
30.3
1.4
2.3
3.0
3.8 risk
4.6 of5.4in-hospital
6.2
7.3
Decile
of baseline
2.3
3.0
3.8
4.6
5.4
6.3
7.3
8.9
mortality
Decile of baseline risk for in-hospital mortality
Conclusions
In the ICU, the SOFA and LODS have greater predictive
validity than qSOFA or SIRS
2001
State of acute circulatory failure characterized by persistent
arterial hypotension unexplained by other causes
Development plan
Systematic review of observational studies
Criteria reported to identify septic shock
Data analysis
Derivation cohort
Surviving Sepsis Campaign Database (SSC)
2005-2010; n = 28,150
Validation cohort
12 hospitals in Pennsylvania (UPMC)
2010-2012; n = 1,309,025
20 Hospitals (Kaiser Permanente Northern California, KPNC)
2009-2013; n = 1,847,165
Systematic review
Systematic review
Multiple criteria used to identify septic shock
Wide heterogeneity
4-fold variation in mortality
Delphi process
Circulatory dysfunction
Hypotension after adequate fluid resuscitation
Outcome
Acute hospital mortality
vasopressor
lactate >2
Prevalence
(SSC)
Group 1
Yes
Yes
Yes
42.3%
Group 2
Yes
Yes
No
21.2%
Group 3
Yes
No
Yes
1.2%
Group 4
No
No
Yes
17.3%
Group 5
No
hypotension
pre-fluid
No
Yes
14.3%
Group 6
Yes
No
No
0.8%
Conclusions
Definition
Septic shock is defined as a subset of sepsis in which
underlying circulatory, cellular and metabolic abnormalities are
associated with a greater risk of mortality than sepsis alone
Clinical criteria
Hypotension requiring use of vasopressors to maintain MAP
65 mmHg and having a serum lactate >2 mmol/l persisting
despite adequate fluid resuscitation
Mervyn Singer
University College London, London, UK
Task Force Co-chair
Soft launch
talking publicly for >1 year really useful feedback
extensive informal peer review
A pragmatic offering
there is no absolute biomarker (yet) for sepsis or septic shock
generalizability - readily measurable identifiers that best capture
conceptualisation of sepsis
SOFA Score
1
Neurological
(GCS)
13-14
10-12
6-9
<6
Respiratory
(P:F ratio)
<400
<300
<200
<100
(+ resp support)
(+ resp support)
<70
dopamine 5 or
dobutamine (any dose)
dopamine >5
or EPI 0.1
or NOREPI 0.1
dopamine >15
or EPI >0.1
or NOREPI >0.1
110-170
171-299
Haematological
(platelets)
<150
<100
<50
<20
Liver
(bilirubin)
20-32
33-101
102-204
>204
Variables/points
Cardiovascular
(systolic BP)
Renal
(creatinine or UO)
300-440
>440
(or <500 ml/day) (or <200 ml/day)
42.3
hypotension alone
30.1
25.7
18.7
Developing world
many lack ability to measure lactate or SOFA criteria
Coding
Acknowledgements
Task Force members
ESICM - Daniel de Backer, Maurizio Cecconi, Jean-Daniel Chiche