blood purification in the icu state of the art

Blood Purification in the ICU:
State of the Art
A/Prof. Rinaldo Bellomo
Austin & Repatriation Medical Centre
Melbourne
Australia
Similarities between sepsis and renal failure
感染与肾功能衰竭之间的相似之处
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The Mediators of Sepsis
(the Humoral Theory of Sepsis)
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The CRRT Membranes
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CRRT and complement
0
100
200
300
400
500
600
700
t 0 t 4 t 12
C3a
C5a
ng/ml for C3a
(/ 10 for C5a)
Time on CVVH at 2L / h UF rate
p < 0.001
p < 0.01
C3a SC = 0.2
C5a SC = 0.02

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TNF levels: CVVH vs. CVVHD
-50
0
50
100
150
200
1 2 3 4 5 6 7 8 9 10
CVVHD
CVVH
p < 0.02
PATIENTS
%
Change
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

High Volume Hemofiltration
•
The term was first used by Grootendorst in
1992
•
Animal experiments in pigs (weight 36-39 kg)
•
Blood flow 300 ml/min
•
UF flow 6000 ml/hr

•
Replacement fluid given pre-filter
•
Polysulfone filters (Amicon, USA)
•
IV endotoxin over 30 minutes

HVHF and RVEF
0
10
20
30
40
50
60
0 30 60 90 120 150 180 210 240
Time in minutes
RVEF (%)
Control
HVHF
p<0.001
Grootendorst et al, Intensive Care Med 1992

HVHF and MAP
0
20
40
60
80
100

120
140
0 30 60 90 120 150 180 210 240
Time in minutes
MAP in mmHg
Control
HVHF
p<0.001
Grootendorst et al, Intensive Care Med 1992
Effect of septic UF on MAP
0
5
10
15
20
25
30
35
40
0 15 30 45 60 75 90 105 120 135 150
2L Normal UF
2L LPS UF
Change
in MAP
(mmHg)
Grootendorst et al, J Crit Care 1993
p < 0.05
Effect of HVHF on ischemic gut injury
0
1

2
3
4
HVHF
No CVVH
Gut injury
score
Mucosal injury
Sloughin
g
Ulcer
s
Perforatio
n
p < 0.05
Grootendorst et al. Shock 1994

HVHF
•
HVHF may be beneficial in human septic shock
•
If Hct of 30% and blood flow of 300 ml/min and
pre-dilution small solute clearance = approx. 60-
70 ml/min (110ml/kg/hr)
•
In 70 kg patient in pre-dilution need about 11
L/hr of UF rate less if post-dilution but need big
blood flows (>400 ml/min)

HVHF

•
11L/hr of UF is technically demanding/very
difficult in human beings
•
Can we achieve similar results at lower UF rates?
•
Dog experiment in 20 kg dogs and UF rate of
2000ml/min (blood flow 200 ml and pre-dilution)
•
Small solute clearance = approx. 80 ml/kg/hr
Change in MAP after IV LPS
-70
-60
-50
-40
-30
-20
-10
0
5 15 45 90 180
CVVH
Sham
Time after IV LPS (minutes)
MAP
(mmHg)
p < 0.05
Bellomo et al AJRCCM 2000; 161: 1429-1436

HVHF vs. CVVH
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Technique for HVHF
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Cole, Bellomo et al. Intensive Care Med 2001; 27: 978-986
Norepinephrine Requirements:
HVHF vs. CVVH
-30
-25
-20
-15
-10
-5
0
5
10
1 2 3 4 5 6 7 8 9 10
HVHF
CVVH
Change
(µg/min)
over 8 h.
p < 0.02
Cole, Bellomo et al. Intensive Care Med 2001 ; 27: 978-986
% Change in Norepinephrine
Dose: HVHF vs CVVH
-100 -50 0 50
1
3
5
7
9
CVVH
HVHF

% change over 8 h.
Cole, Bellomo et al. Intensive Care Med 2001 ; 27: 978-986
C3a: HVHF (6 L) vs. CVVH (1 L)
0
2
6
8
20
HFHV
CVVH
0
100
200
300
400
500
600
ng /ml
p < 0.017
*
*
TIME (hrs.)
Cole, Bellomo et al. Intensive Care Med 2001 ; 27: 978-986
C5a: HVHF (6 L) vs. CVVH (1 L)
0
5
10
15
20
25

30
0 2 6 8 20
HFHV
CVVH
ng/ml
Time (hrs.)
*
*
*
p<0.017
Cole, Bellomo et al. Intensive Care Med 2001
IL-10 during CVVH
0
10
20
30
40
50
60
70
0 2 6 8 20
pg / ml
TIME (hrs)
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Cole, Bellomo et al. Intensive Care Med 2001
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HVHF:
C3a: Serum vs. UF concentration
0
50

100
150
200
250
300
350
2 6 8
Serum C3a
UF C3a
ng/ml
TIME (hrs.)
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Cole, Bellomo et al. Intensive Care Med 2001
TNF: HVHF vs. CVVH
0
50
100
150
200
250
300
0 2 6 8 20
HVHF
CVVH
pg / ml
TIME (hrs.)
Cole, Bellomo et al. Intensive Care Med 2001
IL-8: HVHF vs. CVVH
0
10

20
30
40
50
60
70
80
90
100
0 2 6 8 20
HVHF
CVVH
pg / ml
TIME (hrs.)
*
p < 0.05
Cole, Bellomo et al. Intensive Care Med 2001

Conclusions
•
HVHF has beneficial short term effects in
human septic shock similar to those in
animals
•
With AN69 and molecules >8-9 kD it results
in adsorptive removal, not filtration of
inflammatory mediators
•
There is now a rationale for phase II studies