The Sepsis Timebomb
James Wigfull
Critical Care and Anaesthesia
Sheffield Teaching Hospitals
Copyright Wigfull 2013
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Time is life
Surviving Sepsis
Guidelines
Empiric broad
spectrum
Antibiotics
Source Control
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Relationship of SIRS, Sepsis
and Infection
PANCREATITIS
BACTEREMIA
POST-PUMP SYNDROME
INFECTION
SIRS
FUNGEMIA
TRAUMA
SEPSIS
PARASITEMIA
BURNS
VIREMIA
OTHER
The ACCP/SCCM consensus Conference Committee, Chest 1992;101:1644-55.
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OTHER
Sepsis and mortality
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Vallés et al. Chest 2003;123:1615–1624
Sepsis and Septic Shock: An
Intensivist’s Immunologic View
Antimicrobials
CARS
Infection
Antiinflammatory
(endogenous)
SIRS
Organ
Injury
Time
van der Poll T, van Deventer SJH. Infect Dis Clin N Am
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RECOVERY
Sepsis and Septic Shock:
Cellular dysfunction/tissue injury
An ID View
Inflammatory response
Shock Threshold
Toxic burden
Microbial load
TIME
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“An Injury Paradigm of Sepsis and Septic
Shock” Prof A Kumar, University of Manitoba
Antimicrobial
therapy
Cellular dysfunction/tissue injury
Inflammatory response
Toxic burden
Microbial load
TIME
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Shock
Threshold
“An Injury Paradigm of Sepsis
and Septic Shock” Prof A Kumar, University of Manitoba
earlier
antimicrobial
therapy
Shock
Threshold
Cellular dysfunction/tissue injury
Inflammatory response
Toxic burden
Microbial load
TIME
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“An Injury Paradigm of Sepsis and Septic Shock”
Prof A Kumar, University of Manitoba
more intense
antimicrobial
therapy
Cellular dysfunction/tissue injury
Inflammatory response
Toxic burden
Microbial load
TIME
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Shock
Threshold
“An Injury Paradigm of Sepsis and Septic
Shock” Prof A Kumar, University of Manitoba
Antimicrobial
therapy
+
Source control
Cellular dysfunction/tissue injury
Shock
Threshold
Inflammatory response
Toxic burden
Microbial load
TIME
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Severe Sepsis Resuscitation Bundle
Bundle element 1: measure serum lactate
Bundle element 2: obtain blood cultures prior
to antibiotic administration
Bundle element 3: administer broad spectrum
intravenous antibiotics within one hour
Bundle element 4a: in the event of hypotension and/or serum
lactate >4mmol/l deliver fluid bolus 20ml/kg crystalloid or
equivalent colloid
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Severe Sepsis Resuscitation Bundle
Bundle element 4b: Apply vasopressors if initial fluid bolus
does not maintain MAP >65mmHg
Bundle element 5: In the event of persistent hypotension
despite fluid resuscitation
a: achieve CVP > 8cmH2O
b: achieve ScvO2 > 70%
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Cumulative Initiation of Effective Antimicrobial
Therapy and Survival in Septic Shock
fraction of total patients
1.0
0.8
survival fraction
cumulative antibiotic
initiation
0.6
0.4
0.2
0.0
time from hypotension onset (hrs)
Kumar et al. CCM. 2006:34:1589-96.
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Running Average Survival in Septic Shock
Based on Antibiotic Delay (n=4195)
1.0
fraction
0.8
0.6
running average survival
cumulative fraction of total survivors
0.4
0.2
0.0
0
20
40
60
AbRx Delay (hrs)
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80
100
17
Odds Ratio of Death
(95% Confidence Interval)
Mortality Risk with Increasing Delays in Initiation of
Effective Antimicrobial Therapy
100
10
1
Kumar et al, CCM. 2006:34:1589-96.
Time (hrs)
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Comparison with other time dependent interventions
NNT
MI
CVA
Trauma
NNT
30
30-40
30
Severe sepsis
6-8
Septic shock
Easy diagnosis
Not recognized early
Clear onset
Insidious onset
Presents to A&E
Often develops on wards
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Door to balloon time and mortality in AMI
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Adapted from Cannon et al. JAMA 2000; 283: 2941-7.
Door to balloon time and mortality in AMI
"Preventable" deaths per year
1600
1400
1200
By
getting door-to-balloon times of
1000
<2h for ALL STEMI patients,
800
we would save
600
4775 lives per year.
400
200
0
0-2h
>2-3h
>3-4h
>4-6h >6-12h
"Preventable deaths"
0
282
1350
1555
1384
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Adapted from Cannon et al. JAMA 2000; 283: 2941-7.
>12h
204
Shock to effective antibiotic time and mortality in septic
shock
90
Percentage of patients
80
70
60
50
40
30
20
10
0
%Mortality
% of patients
0-2h
26.7
26.8
>2-3h
36.1
9.0
>3-4h
36.6
7.8
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>4-6h
46.8
12.8
>6-12h
62.3
18.8
Adapted from Kumar et al. Crit Care Med 2006; 34: 1589-96.
>12h
83.1
24.9
Shock to effective antibiotic time and mortality in septic
shock
"Preventable" deaths per year
20000
18000
16000
14000 shock-to-antibiotic times of <2h
By getting
12000
for ALL septic shock patients,
10000
we would save
8000
32,360
lives
per
year.
6000
4000
2000
0
"Preventable" Deaths
0-2h
0
>2-3h
1093
>3-4h
1000
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>4-6h
3318
>6-12h
8710
Adapted from Kumar et al. Crit Care Med 2006; 34: 1589-96.
>12h
18239
Effect of Failure to Implement Source Control
if Required
100
% total patients
% survival
80
60
40
20
0
Source Control
Implemented
Source Control Not
Implemented
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Cumulative Source Control Implementation and
Survival in Septic Shock
fraction of total patients
1.0
0.8
survival fraction
cumulative source
control implementation
0.6
0.4
0.2
0.0
time from hypotension onset (hrs)
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Mortality Risk with Increasing Delays in
Implementation of Source Control in Septic
Shock
14
Odds Ratio of Death
(95% Confidence Interval)
12
10
8
6
4
2
0
Time (hrs)
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Survival and Rapidity of Source Control
Community
Academic
85
Survival (%)
75
65
55
45
35
25
3
6
9
Source Control Delay (hrs)
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12
15
Source Control/Antimicrobial Interaction and
Survival in Septic Shock
Antimicrobial Initiation Post-Shock
<3h
<6h
Source
Control
Initiation
Post-Shock
6-24 h
> 24 h
3-6 h
>6h
92%
70.3%
44.4%
(n=75)
(n=37)
(n=63)
80.0%
46.0%
19.0%
(n=60)
(n=50)
(n=94)
69.0%
36.0%
13.0%
(n=29)
(n=25)
(n=100)
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hours
Audit of Event timing from SHEWS 2 to theatre for
the deteriorating colorectal patient at NGH from
October 2009 to March 2010
9
8
7
A: SHEWS 2 to SpR review
6
5
C: CT booking to scan
B: SpR review to Antibiotics
D: CTscan to report
4
3
E: Scan to theatre booking
2
F: Booking to arrival
1
0
A
B
C
D
E
F
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Audit of Event timing from SHEWS 2 to theatre for
the deteriorating colorectal patient at NGH from
October 2009 to March 2010
25
20
15
Total time from
trigger to theatre
10
5
0
Survivors
Nonsurvivors
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Conclusions
With the onset of shock – the mortality clock
starts ticking!
Your team need to understand that delivery
of intravenous antibiotics is their
responsibility
Source control – the mortality clock does not
wait for a convenient theatre slot
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