IFAD 2011

1. 11st
International Fluid Academy DayInternational Fluid Academy Day
How can dye-dilution helpHow can dye-dilution help
us?us?
Michael Bauer, MDMichael Bauer, MD

2. Monitoring Plasma Dissappearance Rate of
Indocyanine Green (PDRICG) – how?
pulsatile905 nm
non pulsatile805 nm
non pulsatile905 nm
pulsatile805 nmLEDs
805 nm & 905 nm
Sensor
pulsatile905 nm
non pulsatile905 nm
pulsatile805 nm
non pulsatile805 nm
CICG =
[s]0 10 20 30 40 50
0
10
20
30
40
CICG mg/l

3. PDRICG – what do I monitor?
canalicular membrane
Phase I
Phase II
biotransformation
BilirubinBilirubin
ICG
Phase III
(hepatobiliary transport)
bile
basolateral membrane
Sinusoid
[s]0 10 20 30 40 50
0
10
20
30
40
CICG mg/l
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
Sham
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
Sham

4. PDRICG – what do I monitor?
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
Sham
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
Sham Sham
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
Sepsis
native 0 min 6 min 15 min 30 min 90 min 150 min 300 min
SepsisSepsis SepsisCardiac index [l/min/m²]
0 2 4 6 8
0
10
20
30
40
PDRICG
[%/min]
A. Kortgen, et al. SHOCK, 2009
Cardiac index [l/min/m²]
0 2 4 6 8
0
10
20
30
40
PDRICG
[%/min]PDRICGPDRICG
[%/min]
A. Kortgen, et al. SHOCK, 2009
Interleukin 6 [pg/ml]
1 10 100 1000
0
10
20
30
40
PDRICG
[%/min]
Interleukin 6 [pg/ml]
1 10 100 1000
0
10
20
30
40
PDRICG
[%/min]PDRICGPDRICG
[%/min]

5. Recknagel P, Gonnert FA, Kortgen A et al., in preparation
Mechanisms of cholestasis in sepsis
Impairment of biliary transport - Mrp2
sham
sepsis
D
sham sepsis
sham sepsis
B
*
C
20 µm

6. ICGGalle [µg/ml]
0 200 400 600 800 1000 1200 1400 1600
0
10
20
30
40PDRICG[%/min]
uncomplicated
death / Re-Tx
Liver transplant with T-Drain
A. Kortgen, M. Paxian; M. Werth; P. Recknagel; F. Rauchfuß; A. Lupp; C.G. Krenn; D. Müller; R.A. Claus;
K. Reinhart; U. Settmacher; M. Bauer SHOCK, 2009
Differential susceptibility of the polar membranes
– basolateral / canalicular – of hepatocytes

7. Phase I
Phase II
biotransformation
Bilirubin
ICG
Phase III
(hepatobiliary transport)
bile
basolateral membrane
canalicular membrane
SinusoidSinusoid
Physiology Pathophysiology
PDRICG – what do I monitor?

8. Fig. 1 a The plasma concentration time profile following a single 20 mg dose of Atorvastatin (error bars have been omitted
from a for clarity but the values are presented in Table 1). b The profile for healthy volunteers compared to ICU sepsis patients
in the presence and absence of concomitant administered known inhibitors of the cytochrome P450 3A4 enzyme system
Kruger PS, Freir NM, Venkatesh B, Robertson TA, Roberts MS, Jones M: Intensive Care Med. 2009 Apr;35(4):717-21
What does it imply?
Pharmacokinetics and DILI

9. ICG-Clearance
SOFA-Score
0 20 40 60 80 100
100-Specificity
100
80
60
40
20
0
Sensitivity
n= 254
PDRICG – how can it help?
Sakka SG et al. Chest 2002; 122:1715-1720

10. Correlation IAP - PDR
0
2
4
6
8
10
12
14
4 6 8 10 12 14
IAP (mmHg)
ICG-PDR(%)
Courtesy of Manu Malbrain
Plasma dissapearance rate of Indocyanin-
green before and after epidural anaesthesia
40
30
20
10
0 LUMBAL
40
30
20
10
0 THORACIC
Kortgen et al. EJA 2010.
[%/min]
*
**
PDRICG to monitor liver blood flow

11. How to detect hepatic dysfunction
and response to treatment in the ICU
8
6
4
2
0
-1 1 2 3 4 5 6
days
Bilirubin[mg/L]
24
18
12
6
0
PDR-ICG[%/min]
rhAPC

12. PDRICG – how can it help?
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
ICG-PDR[%]
EVLW[ml/kg]
-1200
-800
-400
0
[ml/day]
fluidbalance
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
days
ICG-PDR
EVLW
Therapeutic conflicts

13. Why (the hell) ICG?
Polymethine dyes

14. t (min)
0 10 20 30 40
Relativedecreaseofspecific
fluorescenceintensity[%]
0
20
40
60
80
100
ICG sham
ICG sepsis
DY635 sham
DY635 sepsis
BA
#
#
#
#
*
*
* * *
*
*
*
*
* *
Specificfluorescenceintensity[%]
Modifying the chemistry of Polymethin dyes:
from ICG to DY 635

15. DY-652
Why (the hell) ICG?
Polymethine dyes
From hepatocellular
to renal function

16. From hepatocellular to renal function
Intravital microscopy of the kidney

17. Dye clearance
to assess liver (organ) function
• determines “functional hepatocyte
reserve”
• are superior to conventional
“static tests” in critical care
• may assist with therapeutic decisions

18. The team