Splanchnic perfusion – Detected but neglected? · Splanchnic perfusion – Detected but neglected? _____ 27 thInternational Symposium on ... NT (%) Admission Day1 ... Zollner et

Speeding up decisions – the right monitoring tools at the right time

Splanchnic perfusion –Detected but neglected?

___________________________________________

27 th International Symposium on Intensive Care and Emergency Medicine

Brussels 2007

Claus-Georg KRENNDept. of Anaesthesia and General Intensive Care, University Vienna

[email protected]

„Splanchnic Region“_______________________________________________

• METNITZ

Liverdysfunction_____________________________________________

liver diseasein critically ill patients

known cirrhosis

reason for admission "liver-failure"

liver-dysfunction bilirubin >2mg/dl

n=691 n=108 n=4146 1.82% 0.28% 10.90%

total incidence: 13%

Bilirubin

n=19.193 n=7345 n=3374 n=1243

61.60% 23.58% 10.83% 3.99%

Patients

…virtual round at the ICU___________________________________________________________

Detected but negle

cted?

…virtual round at the ICU_________________________________________________________

HistorySt.p. ACBGSt.p. thoracotomy for bullous cavern

transfer to normal ward

respiratory failure and hypotonia

transfer to Emergency department

Intubation, „hemodynamic stabilization“ and surgery for thoracic empyema

admission to ICU / Reevaluation (hemodynamic stable, homeostasis deranged)

3

2,11,7

1,1 1

0,8

0,177

0,0910,051 0,051

0

1

2

3

4

5

6

7

8

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

PDR (%/min)Lactat (mmol/l)Noradrenalin (mcg/kg/min)

Admission Day1 Day2 Day3 Day4

… parameters at admission_________________________________________________________

What next ?

3

2,11,7

1,1 1

0,8

0,177

0,0910,051 0,051

0

1

2

3

4

5

6

7

8

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9




What next ?

adequate Monitoring

3

2,11,7

1,1 1

0,8

0,177

0,0910,051 0,051

0

1

2

3

4

5

6

7

8

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9




What next ?

adequate Monitoring

Limon Bedside Test

5,55,2

4,2

4,9

7,6

3

2,11,7

1,1 1

0,8

0,177

0,0910,051 0,051

0

1

2

3

4

5

6

7

8

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9




5,55,2

4,2

4,9

7,6

3

2,11,7

1,1 1

0,8

0,177

0,0910,051 0,051

0

1

2

3

4

5

6

7

8

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9



… clinical course_________________________________________________________

2890

2070

958

402

96

23

4946

51

62

0

500

1000

1500

2000

2500

3000

3500

0

10

20

30

40

50

60

70

GOT (U/l)NT (%)


… clinical course_______________________________________________________

Sometimes …_________________________________________________________

unspecific clinical monitoring_________________________________________________________

Sometimes unspecific clinical monitoring is not enough !______________________________________________________________________________________

Catecholamines and Splanchnic Perfusion___________________________________________________________

Catecholamines and Splanchnic Perfusion___________________________________________________________

Macrohemodynamics≠

regional blood flow

Pathophysiology of Hepatocellular Dysfunction_________________________________________________________

Paxian et al. Faseb J 2003; 17:993

Recovery of hepatocellular ATP and “pericentral apoptosis” afterhemorrhage and resuscitation. Paxian et al., FASEB 2003

Hepatocellular apoptosis can be detected accurately by ICG kineticsand is reversible by early resuscitation

Therapy of I/R induced liver dysfunction____________________________________________________________________________________

Molecular mechanisms of excretory dysfunctionMolecularMolecular mechanismsmechanisms of of excretoryexcretory dysfunctiondysfunction

Normal human liver tissue (surgical waste)

Culture + stimulus(Cytokines, GSH depletion...)

Gene expressionof transporter proteins

Human precision cut liver slices were incubated for 24 h with agents as indicated in aconcentration of 10 ngml-1 for 24 hrs. Gene expression was determined by quantitative real time - PCR in comparison to HPRT as unvaried transcript

* **

** principal transporter for bilirubin* principal transporter for ICG

0,1

1,0

10,0

Log

r a

t i o

OATP1 OATP2 OATP8 MRP3 MRP4 MRP5 MRP8A MRP8B

TNFαPhoroneInterferon gammaInterleukin 1βIL-6IL-10IL-18

Gene expression of basolateral transporter proteinsGene expression of basolateral transporter proteins

clinical surrogates of

regional blood flow

and metabolism

Ultrasound - Doppler_____________________________________________

Dynamic Liverfunction-Testing_______________________________________________________________

J Gastrointest Surg. 2001; 5(3):316-21




Dynamic Liverfunction-Testing___________________________________________________________

Petrolati et al.: Aliment Pharmacol Ther 2003;

Indocyaningreen________________________________________

no metabolisationno enterohepatic uptake

immediate excretioninto the bile

Measurement________________________________________

Calculation of the halftimeof the elimination rate of ICG

Sequence of re-extrapolation rate

ICG - non invasive measurement_____________________________________________________________

ICG - non invasive measurement_____________________________________________________________

Sepsis_______________________________________________

ICG - ER detects hepatocellulardysfunction early in septic shockand correlates with survival

Kimura et al.Crit Care Med 2001; 29:1159

Prognosis_______________________________________

screen and adapt actual medication !!__________________________________________________

„It may seem a strange principle to enunciateas the very first requirement in a hospital thatit should do the sick no harm.“

Florence NightingaleNotes on hospitals / London 1859

treat „early and goal directed“_______________________________________________________________________

Therapeutic options__________________________________

APOPTOSIS NECROSIS

CK 18

the End_______________________________________________

... thank you for your attention

Extracorporeal Detoxification - MARS___________________________________________________________________________________

Apoptosis parameter_______________________________________

-500

0

500

1000

1500

2000

2500

3000

3500

4000

Einh

eite

n

vor

ESLD

control

AOCLF

ALF

Box-DiagrammGetrennt nach: GeneseZeilen-Ausschluß: ck18 alf.xls (importiert).svd

MARS - Monitoring_______________________________________

0

0,1

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0,8

0,9

1

0 0,2 0,4 0,6 0,8 1

1 - Specificity

Sens

itivi

ty

SOFA/PDRa

PDRa

SOFA a

rely on your clinical judgement____________________________________________________________________

get information about the functional (reserve) capacityand prognosis rather than about the „damage“ !!!the trend of functional monitoring tells you most !!!

ALF MARS_______________________________________________

Simvastatin significantly improves portal pressurein cirrhosis

Monitoring______________________________________________

Blood flowFunctionReserve capacity

Prognosis

„…dynamic functional testing“

Background - Hypothesis_______________________________________________

Synthesis,

„CirculationCirculation“

Synthesis,

„CirculationCirculation“

Synthesis, HepatocyteHepatocyte FunctionFunction

SynthesisSynthesisExcretoryExcretory FunctionFunction

DetoxificationDetoxification

„Blood Flow“ / (Micro) Circulation____________________________________________________

Visualisation - Fluorescence____________________________________________________________

Detoxification________________________________________

graded encephalopathy - I.-IV.branched chained aminoacidsAmmonium

Effects of LF on the enzymes in the branched-chain amino acid catabolic pathwayShimomura et al.: Biochem Biophys Res Commun 2004

Detoxification____________________________________

Zollner et al.:Hepatology. 2001, 33:633

Hepatocellular Metabolism___________________________________________________

Metabolism_______________________________________

Background__________________________________

Hepatocellular Metabolism___________________________________________________

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Splanchnic perfusion – Detected but neglected? · Splanchnic perfusion – Detected but neglected? _____ 27 thInternational Symposium on ... NT (%) Admission Day1 ... Zollner et