Treatment support of rhabdomyolysis patients by CytoSorb®

Treatmentsupportof
rhabdomyolysispatientsbyCytoSorb®
DietmarFries
Dept.ForGeneralandSurgicalCriticalCareMedicine
MedicalUniversityInnsbruck
Austria
www.clotwork.at
Partners:
TelHashomerMedical UniversityofTelAviv,Israel
USArmy,FortSamHouton, Texas,USA
Dept.ofBioengineering, Univ.ofSanDiego,USA
Dept.forAnesthesia, Aarhus, Denmark
Dept.forHematology, Kings CollegeLondon, UK
Dept.forTraumaSurgery, Cologne Merheim MedicalCenter,Germany
Financialdisclosure:
Industrialgrants/support/lecture fee
AstraZeneca,AOPOrphan,Baxter,Bayer,Braun,Biotest,CSLBehring,
Cytosorb,DeltaSelect,DadeBehring, Edwards,Fresenius, Glaxo,
Haemoscope, Hemogem, Lilly,LFB-France,Mitsubishi Pharma,
NovoNordisk, Octapharm,Pfizer, TEM-Innovation.
Publicgrants/support
AustrianNationalBankTrust,DeutscheBundeswehr, Ministerium für
Landesverteidigung und Sport, USArmy,USDepartmentofDefense.
Rhabdomyolysis....
Rhabdomyolysis:accumulationofmyoglobininthekidneytubulus.
Myoglobinuria:0.5– 1.5mg/dl
Destructionof200gmuscle:myoglobinplasmalevelof100mg/dl
Myoglobin interactswithTamm-Horsfallproteinandformssolid
aggregatesthatobstructnormalflow.
+++lowbloodpressureanduricacid contributetokidney
impairment.
Consequence:acutetubularnecrosisanddecreasedGFR
Research
Vol 12 No 3
Open Access
A positive fluid balance is associated with a worse outcome in
patients with acute renal failure
Didier Payen1, Anne Cornélie de Pont2, Yasser Sakr3, Claudia Spies4, Konrad Reinhart3,
Jean Louis Vincent5 for the Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators
1Department
of Anesthesiology and Intensive Care, CHU Lariboisière, 2, rue Ambroise – Paré, F-75475 Paris Cedex 10, France
Intensive Care Unit C3-327, Academic Medical Center, University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands
3Department of Anesthesiology and Intensive Care, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany
4Department of Anaesthesiology and Intensive Care, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany
5Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, 808, Route de Lennik, B-1070-Brussels, Belgium
2Adult
Corresponding author: Anne Cornélie de Pont, [email protected]
PatientswithARF
Received: 14 Feb 2008 Revisions requested: 17 Mar 2008 Revisions received: 20 May 2008 Accepted: 4 Jun 2008 Published: 4 Jun 2008
Critical Care 2008, 12:R74 (doi:10.1186/cc6916)
This article is online at: http://ccforum.com/content/12/3/R74
© 2008 Payen et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
(acuterenalfailure):
Abstract
Introduction Despite significant improvements in intensive care
medicine, the prognosis of acute renal failure (ARF) remains
poor, with mortality ranging from 40% to 65%. The aim of the
present observational study was to analyze the influence of
patient characteristics and fluid balance on the outcome of ARF
in intensive care unit (ICU) patients.
Methods The data were extracted from the Sepsis Occurrence
in Acutely Ill Patients (SOAP) study, a multicenter observational
cohort study to which 198 ICUs from 24 European countries
contributed. All adult patients admitted to a participating ICU
between 1 and 15 May 2002, except those admitted for
uncomplicated postoperative surveillance, were eligible for the
study. For the purposes of this substudy, patients were divided
into two groups according to whether they had ARF. The groups
60daymortalitywas
Results Of the 3,147 patients included in the SOAP study,
1,120 (36%) had ARF at some point during their ICU stay. Sixtyday mortality rates were 36% in patients with ARF and 16% in
patients without ARF (P < 0.01). Oliguric patients and patients
treated with renal replacement therapy (RRT) had higher 60-day
mortality rates than patients without oliguria or the need for RRT
(41% versus 33% and 52% versus 32%, respectively; P <
0.01). Independent risk factors for 60-day mortality in the
patients with ARF were age, Simplified Acute Physiology Score
II (SAPS II), heart failure, liver cirrhosis, medical admission, mean
fluid balance, and need for mechanical ventilation. Among
patients treated with RRT, length of stay and mortality were
lower when RRT was started early in the course of the ICU stay.
PayenDetal.;CritCare.2008;12(3):R74.
Conclusion In this
large European multicenter study, a positive
fluid balance was an important factor associated with increased
twiceashighas
amongotherpatients
AcuteRenalFailureinCriticallyIllPatients:
AMultinational,MulticenterStudy
UchinoSetal.;JAMA.2005;294(7):813-818.
Heparin
rhAPC
Albumin
therapeutic options
factor concentrates
†
Antithrombin
Thrombo
modulin
fibrinolysis inhibitors
OPTIMIST: TFPI (Tifacogin): no influence on mortality, increased
numbers of bleeding
✗
Heparin
✗
rhAPC
✗
Albumin
✗
Antithrombin
DIC:
therapeuticoptions
✗
Thrombomodulin
✗
fibrinolysisinhibitors
†OPTIMIST– TFPI(Tifacogin):noinfluenceonmortality,increased
incidenceofbleeding1
1.AbrahamE,etal.JAMA2003;290:238–47
Polymer-Technology
• 300ml filter with a „bead“-design
• Hightech-polymer
• Size selection < 55kD
• Low flow resistance
• 120ml bloodvolume / filling volume
• Pre-filled with sodium-chlorid
Blutfluss
• Gamma-steril, 3 year storage
11
Adsorber
Bloodfl
ow
Nahaufnahme CytoSorb™ Beads
Elektronenmikroskop. Aufnahme
Quelle Fotos: Valenti, I “Characterization of a Novel Sorbent Polymer for the Treatment of Sepsis” 2008
IL-18
IL-1β
TNF-α monomer
HMGB1
IFN-γ monomer
TGF-β
TNF-α trimer
IL-1ra
IL-6
PCT
sFas ligand
MCP-1
sTNFR
IL-13
IL-10
MCP-1 glycosylated
Albumin
IL-8
IL-4
MIP-1α
G-CSF
IFN-γ dimer
kDa
0
10
Hämodialyse
20
30
40
50
60
70
Myoglobin isaglobularproteinwith153Aminoacids
andamoleculemassof17kDA...
Myoglobin
kDa
0
10
Hämodialyse
20
30
40
50
60
70
Not eliminated by CytoSorb®…
No elimination of Immunglobulines
IgG: 150 KD
IgM: 971KD
IgE: 198 KD
IgA: Monomer: 160 KD, Dimer: 385 KD
IgD: 172 KD
18
Not eliminated by CytoSorb®…
Coagulation and complement is not activated
No elemination of Fibrinogen: 340 KD
No elemination of coagulation factors
No elemination of AT III, Prot. C 65 KD
No relevant elemination of Albumin
Small decrease of platelets
19
Not eliminated by CytoSorb®…
20
Not activated by CytoSorb®…
Plasma levels of C3a and C5b-9 as a result of activation of the
complement system do not increase.
Quelle: Kellum JA et al., Feasibility study of cytokine removal by hemoadsorption in brain-dead humans; Crit Care Med. 2008 Jan;36(1):268-72
Besidesomeinterventional clinicaltrials,norandomized, controlled
clinicaltrialshavebeenpublished forthetreatmentofrhabdomyolysis.
Standardtreatmentofrhabdomyolysis:
Ø discontinuation offurther muscleinjury,
Ø prevention ofkidney failureand
Ø identification andmanagementoffurther complications.
Earlyandaggressivevolumeresuscitationisacornerstone (strong
controversyaboutthetypeandvolume offluid butalsoofdiuretics).
Alkalinisationofurineisastandardprocedure (lackofevidence(3).
Itshouldbekeptinmindthatalkalinisation ofurinemaycausesystemic
metabolicalkalosis.
BrownCV,RheeP,ChanL,EvansK,DemetriadesD,VelmahosGC.Preventingrenalfailureinpatientswith
rhabdomyolsis: dobicarbonateandmannitolmakeadifference?JTrauma2004;56:1191-1196.
„Therewasinsufficientevidencetodiscern
anylikelybenefitsofCRRToverconventional
therapyforpeoplewithrhabdomyolysis and
prevention ofrhabdomyolysis-induced AK“
A68year-oldmalewithmyocardialinfarction.
During ongoing CPR:ECMO.
ToweanthepatientfromECMO:LVAD
AfterremovalofECMOandLVAD:thepatient
suffered fromacombination ofsepsis
(chlamydialpneumonia) andlowoutput.
Myoglobin (of 32.189µg/l)andbilirubin
increaseddramatically.
A68year-oldmalewithmyocardialinfarction.
During ongoing CPR:ECMO.
ToweanthepatientfromECMO:LVAD
AfterremovalofECMOandLVAD:thepatient
suffered fromacombination ofsepsis
(chlamydialpneumonia) andlowoutput.
Myoglobin (of 32.189µg/l)andbilirubin
increaseddramatically.
59yo malepatient suffering from:
Ø MOF
Ø acute necrotizing pancreatitis,
Ø lactacidosis,
Ø severe septic shock
Ø massivebleeding/massivetransfusion
Ø acute renalfailure
Ø rhabdomyolysis
Ø ARDS
Ø DICwith pulmonary bleeding
Ø liver failure
Ø pneumonia
Ø colitis
59yo malepatient suffering from:
Ø MOF
Ø acute necrotizing pancreatitis,
Ø lactacidosis,
Ø severe septic shock
Ø massivebleeding/massivetransfusion
Ø acute renalfailure
Ø rhabdomyolysis
Ø ARDS
Ø DICwith pulmonary bleeding
Ø liver failure
Ø pneumonia
day
Bilirubin(mg/dl)
Ø colitis
22.2.15
28,5
23.2.15
24,95
24.2.15
20,71
25.2.15
18,67
26.2.15
8,51
27.2.15
11,79