use of cytokine adsorbtion in acute severe...
TRANSCRIPT
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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…