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Andreas Faltlhauser DEAAKlinikum Weiden, Germany

Cytosorbents User MeetingBruxelles14.03.2016

Use of Cytokine adsorbtion in acute severe Pancreatitis

“Time is of the Essence“

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Andreas Faltlhauser, DEAAInterdisziplinäre ITS 83

Klinikum Weiden

Conflict of Interest:

• Fa. Orion Medical

• Fa. Köhler Pharma

• Fa. Pulsion Medical

• Fa. CLS Behring

• Fa. Cytosorbents

Use of Cytokine adsorbtion in acute severe Pancreatitis

“Time is of the Essence“

Cytosorbents User MeetingBruxelles14.03.2016

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• „Hit first, hit hard“• „Staying awake is staying

alive in ICU“• And many more …

• „Nip it in the bud….!“ • „Primum nihil nocere“

Paradigms in Modern Intensive Care

„Principiis obsta“, OvidHippokratischer Eid

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• Invasive Therapy• Large Foreign Surfaces• Scarce Research Data • Abx, T3, Cortisol-Levels?• But also:• Fascinating Concept• Logical Pathophysiology

Conservative Strategyvs. Intervention

Cytosorb®

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More Questions thanAnswers….

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But what we know:

Pancreatits and Burns

„…produce the worst in man!“Rob Boots (ANCICS CRM Meeting 2010)

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Balance inPro-Anti Inflammation

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…back to Pancreatitis

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What do the Guidelines say?(IAP/APA 2013 – ACG 2013 – AWMF Nutrition2013)

Hints for:

• Basic Suupport?• Diagnostics• Interventions (esp. in biliary

ethiology)• Nutrition• Therapy of local complications

… and how to deal with acuteinflammatory reactions?

The Dilemma

Two exemplary Patients – Two contrary Courses

Pat 1 ♂ 54 yoAufnahmeAPACHE2: 22

24h

Pain - 14 h -

Lipase 10219 U/l -

Ca+ 2,03 mmol/l 2,08 mmol/l

Hct 51% 35%

Bili 0,8 mg/dl 1,1 mg/dl

GOT 127 225

INR 1,1 0,9

Bilanz - +11200 ml

RIFLE I L

Atmung BiPAP CPAP ASB

FiO2 0,7 0,45

CVVH CiCa CiCa

Cytosorb + 4,5h

Pat 2 ♂ 49 yoAufnahme APACHE2: 25

24h

Pain - 44 h -

Lipase 8345 U/l -

Ca+ 1,79 mmol/l 1,98 mmol/l

Hct 59% 43%

Bili 1,4 mg/dl 3,9 mg/dl

GOT 443 2893

INR 1,6 3,4

Bilanz - +13450 ml

RIFLE L L

Atmung BiPAP BiPAP

FiO2 1,0 1,0

CVVH CiCa CiCa

Cytosorb + 8 h

The DilemmaTwo exemplary Patients – Two contrary Courses

2,52,1

3,4 3,53,9

1,4 1,2

1,81,5 1,3

0 6 12 18 24

Hämodynamik

CIPat1(l/m²KOF) CIPat2(l/m²KOF)

A third CasePancreatitis with acute Peritonitis en route

Pat 3 ♂ 32yoPräOP

APACHE2: 2124h

APACHE2: 30

Pain VAS 8 VAS 2

Lipase 433 -

Ca+ 2,02 mmol/l 2,11 mmol/l

Hct 41% 34%

PCT 0.29 0,44

GOT 459 278

INR 0,9 1,0

Bilanz - + 7830

RIFLE R R

Atmung Spontan Spontan

FiO2 0,3 0,42

CVVH - -

Cytosorb - -

On Admission

Three weeks later…Acute Peritonitis post interventional

Pat 3 ♂ 32yopräOP

APASCHE2: 1424h

APASCHE2: 25

Ca+ 2,12 mmol/l 2,07 mmol/l

Hct 41% 22%

Bili 2,8 mg/dl 4,4 mg/dl

GOT 178 1243

INR 1,1 2,3

RIFLE R L

PCT 1,24 23,27

Leukos 11,3 34,8

Temp 37,8 40,4

Atmung Spontan BiPAPP 20

FiO2 0,42 1,0

CVVH keine CiCa

Cytosorb nein +2h postOP

Typical severe septic Course

2,52,1

3,4 3,53,9

0 6 12 18 24

Hämodynamik

CIPat1(l/m²KOF)

6,25,8

3,42,9

0,5

0 6 12 18 24

Noradrenalinbedarf

CI Pat1 (l/m²KOF)

1,2

12,1

10,1

5,2

2,2

0 6 12 18 24

IL 6 Verlauf

IL6 Pat1 (pg/mlx10³)

NA (µg/kg/h)

Timing is of the Essence

… what we know as of March 14th 2016

• Proof of Safety: Cytoadsorbtion can be performed safely

• Proof of Concept:IL 6 as key inflammatory marker can besignificantly reduced

• Cytoadsorbtion aids to reducecatecholamine use and improves global haemodynamics

Timing is of the Essence

… what we don´t know as of March. 14th 2016:

• Does Cytoadsorbtion provide• Reduction of Morbidity• Reduction of Mortality

• Dosing of Cytoadsorbtion?• Drug Dosing under

Cytoadsorbtion?• Cost Benefit Evaluation?

+•PACIFIC• Pancreatitis

CytoSorbInflammatoryCytokine Removal

Success

+ Intervention:

n Two consecutive 24h courseshaemoperfusions withCytoSorb-Filter.

n Thereafter further CytoSorbtreatment on the disgression ofthe treation team.

+Primary Endpoint

n Improvement ofVasopressor DependencyIndex [Cruz, JAMA 2009] >20%.

n In catecholamin-freePatients: Improvement ofCardiac Power Index >20%

+Main secondary Endpoints

n ICU-, 28d- and Hospital-Mortality vs. matchte controls without Cytokin-Elimination (EAGLE-Trial of DFG)

n Cytokine levels in serum pre andpost Intervention

n SOFA-Score pre and post Intervention

n Cardiac-Power-Index

+Further Endpoints

n Ventilator free days

@ 28days

n ARF using AKIN criteria

@ 28 days

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Concentration on the main thingisn´t always that easy…