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The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels. - PowerPoint PPT PresentationTRANSCRIPT
Anand Kumar, Cameron Haery, Bhanu Paladugu, Aseem Kumar, Simon Symeoneides, Leo Taiberg, Jailan Osman, Gordon Trenholme, Steven M. Opal, Roy Goldfarb, and Joseph E. Parrillo
ABSTRACT Background. This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock. Methods. Surgical implantation of an E. coli (O18:K1:H7)laced, gelatin capsuleencased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF), interleukin (IL)6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment. Results. A critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in 20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine
Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine
Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 1824 h after implantation. Antibiotic treatment initiated 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF-, and IL-6 levels. Conclusions. The timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated. (J Infect Dis 2006; 193: 251-258)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate
and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate
and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Sham infected
0 hr
12 hr
15 hr
18 hr
No RX
6 hr
Hours after implantation
Cu
mu
lati
ve s
urv
ival
rat
e (%
)
0 12 24 36 48 60 72 84 96
0
20
40
60
80
100
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*††
†††
†
††
†
†
†† †
HR
(b
ea
ts/m
in)
CO
(m
L/m
in)
MA
P (
mm
Hg
)S
V (L
)
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Mean cardiovascular responses in untreated septic mice (white circles; n = 10) and sham-infected control mice (black circles; n = 8). Measurements taken of heart rate (HR; A), stroke volume (SV; B), cardiac output (CO; C), and mean arterial pressure (MAP; D). Group comparisons made using repeated-measures analysis of variance; point comparisons made using least-squares method. *P < .05, vs. sham-infected control mice at equivalent time point; P < .0001, vs. sham-infected control mice at equivalent time point. Error bars indicate SEs.
Kumar et al. J Infect Dis 2006; 193: 251-258
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
eats
/min
)C
O (
mL
/min
)
MA
P (
mm
Hg
)S
V (L
)
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Duration of Hypotension before Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock:
Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
ea
ts/m
in)
CO
(m
L/m
in)
MA
P (
mm
Hg
)S
V (L
)
Hours after implantation
Hours after implantation Hours after implantation
Hours after implantation
P=.0364P<.0001
P<.0001
P<.0001
D
BA
C
70
60
50
40
30
20
100 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96 0 12 24 36 48 60 72 84 960 12 24 36 48 60 72 84 96
500
400
300
200
100
25
20
15
10
5
0 20
40
60
80
100
120
*
*******
*†††††
†
††
†
†
†† †
HR
(b
ea
ts/m
in)
CO
(m
L/m
in)
MA
P (
mm
Hg
)S
V (L
)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Mean serum lactate (A), tumor necrosis factor (TNF) (B), and interleukin (IL)6 (C) levels in untreated septic mice (white inverted triangles) and sham-infected control mice (black circles; n = 8 mice/group). Group comparisons were made using repeated-measures analysis of variance; point comparisons were made using the least-squares method. Septic mice vs. sham-infected control mice, P < .0001 in all cases. P < .0001, vs. sham-infected control mice at the equivalent time point. Error bars indicate SEs.
Kumar et al. J Infect Dis 2006; 193: 251-258
Sham-infected miceSeptic mice
500
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8000
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4000
2000
0
0
2
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14
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Ser
um
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α (
pg
/mL
)S
eru
m IL
-6 (
pg
/mL
)
Sham-infected miceSeptic mice
Sham-infected miceSeptic mice
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258500
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14Sham-infected miceSeptic mice
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
500
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0
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14Sham-infected miceSeptic mice
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Sham-infected miceSeptic mice
500
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100
0
8000
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0
0
2
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14
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
Sham-infected miceSeptic mice
Sham-infected miceSeptic mice
Sham-infected miceSeptic miceSham-infected miceSeptic mice
500
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100
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0
0
2
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14
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
500
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0
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0
0
2
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Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
Sham-infected miceSeptic miceSham-infected miceSeptic mice
Sham-infected miceSeptic miceSham-infected miceSeptic mice
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Sham-infected miceSeptic mice
500
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200
100
0
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6000
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2000
0
0
2
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14
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
Sham-infected miceSeptic mice
Sham-infected miceSeptic mice
Sham-infected miceSeptic miceSham-infected miceSeptic mice
500
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0
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0
0
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Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
500
400
300
200
100
0
8000
6000
4000
2000
0
0
2
4
6
8
10
12
14
Hours after implantation
Hours after implantation
Hours after implantation
0 h 6 h 12 h 18 h 24 h
24 h18 h
18 h
12 h
12 h
6 h
6 h 24 h
0 h
0 h
Se
rum
lac
tate
(m
mo
l/L
)S
eru
m T
NF
-α(p
g/m
L)
Se
rum
IL-6
(p
g/m
L)
Sham-infected miceSeptic miceSham-infected miceSeptic mice
Sham-infected miceSeptic miceSham-infected miceSeptic mice
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
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0
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0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(p
g/m
L)
Ser
um
lact
ate
(mm
ol/L
)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Mean serum lactate (A), tumor necrosis factor (TNF) (B), and interleukin (IL)6 (C) levels in mice given antibiotic treatment 6 (black bars), 12 (light gray bars), or 18 (dark gray bars) h after implantation (n = 6 mice/group). Highly significant differences in responses between groups existed (P < .0001). Group comparisons were made using repeated-measures analysis of variance; point comparisons were made using the least-squares method. *P < .05, vs. septic mice before antibiotic treatment at the same treatment initiation time point; P < .0001, vs. septic mice before antibiotic treatment at the same treatment initiation time point. Error bars indicate SEs.
Kumar et al. J Infect Dis 2006; 193: 251-258
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
cta
te (
mm
ol/L
)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
cta
te (
mm
ol/L
)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Treatment 6 h after implantationTreatment 12 h after implantationTreatment 18 h after implantation
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
Before treatment 3 h aftertreatment
6 h aftertreatment
12
10
8
6
4
2
0
700
600
500
400
300
200
100
0
8000
6000
4000
2000
0Ser
um
IL-6
(p
g/m
L)
Ser
um
TN
F-
(pg
/mL
)S
eru
m la
ctat
e (m
mo
l/L)
Treatment 0 h after implantation
Treatment 6 h after implantation
Treatment 12 h after implantation
Treatment 18 h after implantation
6 h after treatment
6 h after treatment
Beforetreatment
Beforeimplantation
0.01
0.1
1
10
100
1000
Se
rum
LP
S (
pg
/mL
)
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate
and Inflammatory Cytokine Levels
The Duration of Hypotension before the Initiation of Antibiotic Treatment Is a Critical Determinant of Survival in a Murine Model of Escherichia coli Septic Shock: Association with Serum Lactate
and Inflammatory Cytokine Levels
Kumar et al. J Infect Dis 2006; 193: 251-258
0h 6h 12h 18h 24h
COSV↓Lactate↑↑
Early septicshockMAP↓
Lactate↑
HR↑TNF-↑
IL-6↑
Implantation