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: yuichinchin713@yahoo.co.jp

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 )

3

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%

4

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

5

PMX cartridge( Toraymyxin® ,Toray industries, Tokyo, Japan)

6

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.

7

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 ).

8

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 -

9

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

10

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

11

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＜

12

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

13

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

14

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

15

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.