Influence of Direct Hemoperfusion Using Polymixin B Immobilized Fiber ( PMX- DHP )
on Heart Rate Variability in Patients with Septic Shock
Y. Kuroki, T. Ikeda, K. Ikeda, T. Ueno, T. Yokoyama, K. Yoshikawa
Division of Acute & Critical Care Medicine, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan
E-mail: [email protected]
2
Heart Rate Variability ( HRV )
• Frequency domain measures consist of power spectral analysis of the heart rate time series, usually modeled with a Fast Fourier Transform.
• Entropy is a statistic value that quantifies the amount of regularity in a time series.
HRV monitor( Memcalc®, Suwatrust, Tokyo, Japan )
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Normal values and Characters of HRV
Frequency Meanings Normal values
LF 0.04-0.15 Hz sympathetic and parasympathetic activity
1170 ± 416 ms2
HF 0.15-0.4 Hz parasympathetic activity
975 ± 203 ms2
LF/HF sympathetic / parasympathetic balance
1.5 - 2
VLF <0.04 Hz hormonal function 1782 ± 965 ms2
Entropy cardiac regularity 40 - 60%
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Heart Rate Variability and Septic shock
Authors Results
P. J. Godin, et alCrit Care Med 1996
LPS infused to healthy adults caused LF↓, HF ↓, VLF↓, entropy↓
D. Annane, et alAm J Respir Crit Care Med 1999
LF↓ at the onset of septic shock
T. Moriguchi, et alNippon Rinsho (Japanese) 2004
LF↓, HF↓2hrs before the occurrence of septic shock
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PMX cartridge( Toraymyxin® ,Toray industries, Tokyo, Japan)
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Hypothesis
• PMX – DHP increases HRV in patients with septic shock.
• Hemodynamic status in patients with septic shock correlates HRV.
• Inflammatory response decreases HRV in patients with septic shock.
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MethodsPatients selection • Ten patients who were diagnosed as septic shock defined by American College of
Chest Physicians/Society of Critical Care Medicine were included. • All patients were treated with PMX cartridge ( Toraymyxin® ,Toray industries, Toky
o, Japan )• Two patients were excluded because they had atrial fibrillation.
HRV monitoring• HRV monitor : Memcalc®, Suwatrust company, Tokyo, Japan• HRV values were shown as average of 5 min recordings.
Measurement of inflammatory cytokine & chemokine• Blood samples were drawn from arterial catheters just before and immediately aft
er PMX-DHP.• Serum Interleukin ( IL )-6 and IL-8 were measured with each sample.• IL-6 measurement was performed by chemiluminescent enzyme immunoassay ( C
LEIA ).• IL-8 measurement was performed by enzyme linked immunosorbent assay ( ELIS
A ).
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Patients characteristicsAge
Gender Infection Laparotomy
APACHE II SOFA
Norepinephrine
Vasopressin Vasopressor Number of Outcome
focus ( µg/kg/min
) ( U/min) Score* PMX
58 M peritonitis yes 22 9 0.3 0.02 5 2 survive
88 F peritonitis yes 22 10 0.3 0 4 1 survive
64 FGBS
infection yes 29 11 0.3 0.04 6 2 survive
66 F pyelonephritis no 29 14 0.3 0.01 5 2 survive
76 M pyelonephritis no 23 8 0.3 0 4 2 survive
56 F peritonitis yes 11 6 0.1 0 3 1 survive
52 F peritonitis yes 11 6 0.2 0 4 2 survive
84 M peritonitis yes 24 12 0.2 0 4 1 survive* Vasopressor score is the sum of these points
Point 1 2 3Dopamine
( µg/kg/min )1 - 5 5 - 10 10 -
Norepinephrine
( µg/kg/min )0.01 - 0.05 0.05 – 0.1 0.1 -
Vasopressin
( U/min )None 0.01 - 0.02 0.02 -
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HRV during PMXEntropy
0
10
20
30
40
50
0 min 30 min 60 min 90 min 120 min
time from the initiation of PMX
Entr
opy
( %
)
†
‡
‡
LF
- 1
0
1
2
3
4
5
6
0 min 30 min 60 min 90 min 120 min
time from the initiation of PMX
ln L
F (
mse
c2 )
†
HF
- 2
- 1
0
1
2
3
4
5
6
0 min 30 min 60 min 90 min 120 min
time from the initiation of PMX
ln H
F (
mse
c2 )
†
VLF
0
1
2
3
4
5
0 min 30 min 60 min 90 min 120 min
time from the initiation of PMXln
VLF (
mse
c2 )
† p < 0.05, ‡ p < 0.01 vs 0 minRepeated measure ANOVA, Bonferroni method
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Mean Arterial Pressure / Vasopressor Score
05
1015202530354045
0 min 30 min 60 min 90 min 120 min
Time from the initiation of PMX
MA
P/V
asopr
ess
or
Score
( m
mH
g )
‡
‡ p < 0.01 vs 0 minRepeated measure ANOVA, Bonferroni method
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Correlation between MAP/VS and HRV
0
20
40
60
80
100
120
- 2 0 2 4 6 8
ln LF ( msec2 )
MA
P/V
asop
ress
or S
core
( m
mH
g )
R = 0.368p = 0.001
0
20
40
60
80
100
120
- 4 - 2 0 2 4 6 8
ln HF ( msec2 )
MA
P/V
asop
ress
or S
core
( m
mH
g )
R = 0.261p = 0.026
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Entropy ( % )
MA
P/V
asop
ress
or S
core
( m
mH
g )
R = 0.408p 0.001<
0
20
40
60
80
100
120
0 2 4 6 8
ln VLF ( msec2 )
MA
P/V
asop
ress
oor
Sco
re (
mm
Hg
)
R = 0.435p 0.001<
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Changes of IL-6 & IL-8
IL-6
0
1
2
3
4
5
pre PMX post PMX
log
IL-6
( p
g/m
l )
p = 0.005
IL-8
0
1
2
3
4
pre PMX post PMX
log
IL-8
( p
g/m
l )
p = 0.035
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Correlation between IL-6 and HRV
0
1
2
3
4
5
6
0 10 20 30 40 50 60
Entropy ( % )
log
IL-6 (
pg/
ml )
R = - 0.417p = 0.027
0
1
2
3
4
5
6
- 2 0 2 4 6 8
ln LF ( msec2 )
log
IL-6 (
pg/
ml )
R = - 0.491p = 0.008
0
1
2
3
4
5
6
- 4 - 2 0 2 4 6 8
ln HF ( msec2 )
log
IL-6 (
pg/
ml )
R = - 0.500p = 0.007
0
1
2
3
4
5
6
0 2 4 6 8
ln VLF ( msec2 )
log
IL-6 (
pg/
ml )
R = - 0.145p = 0.462
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Correlation between IL-8 and HRV
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
0 10 20 30 40 50 60
Entropy ( % )
log
IL-8 (
pg/
ml )
R = - 0.491p = 0.009
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
- 2 0 2 4 6 8
ln LF ( msec2 )
log
IL-8 (
pg/
ml )
R = - 0.588p = 0.001
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
- 4 - 2 0 2 4 6 8
ln HF ( msec2 )
log
IL-8 (
pg/
ml )
R = - 0.553p = 0.003
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
0 2 4 6 8
ln VLF ( msec2 )
log
IL-8 (
pg/
ml )
R = - 0.210p = 0.292
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Conclusions
• PMX-DHP might improve hemodynamic status by restoring autonomic activity in the patients with septic shock.
• IL-6 and IL-8 might suppress autonomic activity in the patients with septic shock.