Dept. of Nephrology and Dialysis, Research Hospital “Casa … · 2020-02-18 · Bosch X et al....

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CytoSorbandrhabdomyolysisandkidneyfailure

FilippoAucella,M.D.Dept.ofNephrologyandDialysis,ResearchHospital“CasaSollievodellaSofferenza”

SanGiovanniRotondoITALYCertifiedISO9001:2008

Destructionordisintegrationofstriatedmusclecellsresultingintheleakageoftheintracellularmuscleconstituentsintocirculationand

extracellularfluid.

•  Creatinekinase(CK)

•  Myoglobin

•  Potassium,Phosphorus

•  Transaminase

•  LDH

BoschXetal.Rhabdomyolysisandacutekidneyinjury.NEnglJMed2009;361:62-72 2

Rhabdomyolysis: definition Huerta-AladinAL.CriticalCare2005,9:158-169

Ospedale“CasaSollievodellaSofferenza”,IRCCS,SanGiovanniRotondo

Myoglobin

3

!  MyoglobinisadarkredcytoplasmichemoproteinthatbindOxygenonahemegroup

!  HighaffinityforOxygen

!  17.800Da

!  PhysiologicalPlasmaLevels:0-0,003mg/dl

Pathogenicfactorinrhabdomyolysis-inducedAKI



Rhabdomyolysis: Pathophysiology

5

Huerta-AladinAL.CriticalCare2005,9:158-169;Chavezetal.CriticalCare(2016)20:135

Myocytedestruction


Complicationsofrhabdomyolysis


TheOchsnerJournal15:58–69,2015

Rhabdomyolysis and AKI

7

AcuteKidneyInjury

!  Among10-50%ofpatientswithrhabdomyolysisdevelopAKI

Huerta-AladinAL.CriticalCare2005,9:158-169

!  AKIassociatedwithmyoglobinuriaisthemostseriouscomplicationofrhabdomyolysis



PathophysiologicalMechanismsinRhabdomyolysis-Induced

AcuteKidneyInjury


"  Renalvasocostrictionthroughhypovolemiaandactivationofcytokinecascade

"  Tubularobstructionthroughtheproductionofpigmentedcasts

"  Directtoxicityofmyoglobin

Focus:Preservetherenalfunction

10

" Dialysistechniqueshaveshownpoorefficacyintheremovalofcirculatingmyoglobin.

" Strategiesarerequiredfortherapidremovalofcirculatingmyoglobinandothermuscleenzymesfromtheblood.


•  Plasmaexchange•  Intermittenthemodialysis•  Conventionalhemodialysis

Unfortunately,thesetherapieshavelimitedsuccessinmyoglobinremoval

Extracorporeal Therapies

"  Itisimportanttopreventfurtherdamagesbyreducingthecirculatingmyoglobin

RoncoC.CriticalCare.2005;9(2):141-142.

Huerta-AladinAL.CriticalCare2005,9:158-169

•  Continuosveno-venoushemofiltrationorhemodiafiltrationwiththeuseofsuperhighfluxfiltersandhighvolumesofhemofiltration

Noevidenceandtheeffectonoutcomesisunknown


12Ospedale“CasaSollievodellaSofferenza”,IRCCS,SanGiovanniRotondo

13

mortalityandadverseeventsdidnotdiffersignificantlyamongpatientstreatedwithCRRTandconventionaltherapy



Newsolutions:WhyAdsorption?

Adsorption:fromtheLatinadsorbere,isachemical-physicalphenomenon

thatconsistsintheaccumulationofoneormorefluidorgaseousmoleculesonthesurfaceofacondensate.

Themoleculesestablishachemical-physicalinteractionbetweenthemontheseparationsurfacebetweentwodifferent

phases

Basedonhydrophobicinteractions:Thehydrophobicinteractionsare,liketheintermolecularforcesthatholdpolarmoleculestogether,electrostaticforces.They

canbeclassifiedintwotypes:hydrophobicinteractionsthatareestablishedonlyforthe

simplereasonthattheapolarmolecules,toavoidcontactwithwater,"fallback"onthemselves

vanderWaalsforces,electrostaticforcesbetweentemporaryandinduceddipoles


16

0 kDa 10 20 30 40 50 60 70

TNF-α Trimer

IFN-γ dimer

IL-6 sFas Ligand

MCP-1 (Glycosylated) Albumin

IL-8 MIP-1α

IL-18

sTNFR

G-CSF IL-4

Free Hemoglobin

Myoglobin Bilirubin

Hemodialysis

HMGB1 TGF-β

CytoSorb®

MCP-1 IL-13 IL-10

IL-1a TNF-α Monomer IFN-γ Monomer

IL-1Ra

Hydrophobicmoleculesupto55-60kDa


Performance

2mqvs40.000mqX6

In vitro evidence

Saline

Siero


UseofCytosorbinapatientwithipermyoglobinemiafollowingacuteischemiaoftherightlowerlimb

•  68-year-oldFemale

•  Mitralvalvereplacementinminitoracotomy

•  Acuteischemiaoftherightlowerlimb

•  DayPO5:myoglobinemia>20.000ng/ml,CPK=7648U/l

# Surgicalresolutionofischemiaproblem

# StartCVVHDF(Qb:150ml/min;Quf:100ml/h,

Qd:1500ml/h,WL:100ml/h)+Cytosorbfor4days

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"  StabilizationofMyoglobinandCPKlevels"  RenalFunctionImprovement" Normaldiuresisachieved

Cytosorb

FrancescoGreco,MatteoMelchionda,FrancescoDistaso,MinervaMedicaVol.108,Suppl2,Aprile2017


•  35-y-oMale

•  Politraumaaftercocaineintoxication:multiplefractures,rhabdomyolysisandacutekidneyinjury

•  T0:Myoglobin:>63.000ng/ml;CPK:>54.000U/L,Creatinine:2,87mg/dl

•  CVVHD+Cytosorbfor48h

•  After48h:Myoglobin:11.570ng/ml;CPK:6.586U/L

19

T0>63.000ng/ml

T48>11.570ng/ml

"  StabilizationofMyoglobinandCPKlevels"  RenalFunctionImprovement" Normaldiuresisachievedafter6days

ArboP,CarraroM,BiancoF,DimasoV,GeriniU,BerlotG,BoscuttiG.MinervaMedicaVol.108,Suppl2,Aprile2017

UseofCytosorbinapatientwithAKIassociatedtorhabdomyolysis


Caseseries:3malepatientswithcrushsyndromeofdifferentseverityaftercentralItalyhearthquake(Averagetimeunderrubbles:9hours):#  HighHematocritandhemoglobyn#  Hyperkaliemia#  Creatininemia#  Myoglobin>12.000ng/ml:Technicallimitoftheinstrumentsinthefirstdays#  IncreaseofLDH,GPT,GOT#  Anuria

Patient1 Patient2 Patient3

Hemoglobyn(g/dl) 16,9 18,8 18,4Hematocrit(%) 51 55,9 56Myoglobin(ng/ml) >12.000 >12.000 >12.000CK(U/l) 14.500 300.390 156.920LDH(U/l) 883 - 8.615Potassium(mmol/l) 6,14 6,14 6,7Creatinine(mg/dl) 1,22 1,18 2,21

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ParametersattheadmissioninER

"  StandardtreatmentforRhabdomyolysis

"  CRRTwithhighcut-offfilterinthefirst4days

NewtreatmentinRhabdomyolysiswithAKIinpatientswithcrushsyndromeafterhearthquakeinItaly


Results

CRRT+HCOfiltersNondetectableMyoglobinlevels>12.000ng/ml

!  Day0-4:CRRTwithhighcutofffilters:noevidenceofsignificantmyoglobinrapidreduction

!  Day4:StartofCytosorb(average:3daysoftreatment)

"  RapidReductionofboth,MyoglobinandCPK

"  RenalFunctionRecovery"  NormalDiuresisRecovery


•  34y-omale,bodybuilder

#  StandfordtypeAaorticdissection,massiveARandcardiactamponade.•  CPBtime612min,Xclamp340minutes•  Aorticarchreplacementandsovra-aorticvesselsreimplantation

#  SeverebiventricularfailureduringCPBweaning:peripheralV-AECMO

OnICUadmission:

#  Lactate20#  HR110/min,MAP62mmHg,Norepinephrine0.6mcg/kg/min,

Epinephrine0.085mcg/kg/min,Levosimendan0.05

#  Anuria:CVVHDFstartedinPOD1#  Hyperkalemia(7,3mM/L)andpeakofmyoglobin860.000ng/ml

andCPK511.000UI/L

#  Bilirubintot2.87,AST121022

!  Hemodynamicinstability

!  LiverDysfunction!  Rhabdomyolysis!  MOF

Cytosorbafter5days

ExperienceofAziendaSanitariaUniversitariaIntegrata-Udine


Experience of Azienda Sanitaria Universitaria Integrata - Udine

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T024h48h72h96h5d6d7dUI/L0

100000

200000

300000

400000

500000

600000

700000 CPK

ng/mL T024h48h72h96h5d6d0

100000

200000

300000

400000

500000

600000

700000

800000

900000

1000000 Myoglobin

"  Reductionofboth,MyoglobinandCPK,toprotectkidney

"  Reductionofvasopressors(Norepinephrine/Epinephrine)

CPB

mcg/kg/min

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

T024h36h

Norepinephrine

Epineprhine

Vasopressors


CytosorbInRhabdomyolisis:clinicalexperiencesInstitution ClinicalCondition N°Treatments/

totaldurationMYBInitialValue

MYBFinalValue

OtherData

UniversityofVienna

Legionella-PneumoniaAssociated

Rhabdomyolysis

2treatments/24h

18.390ng/dl 8.352ng/dl-  CytosorbinHP-  RenalFunction

Improvement

UniversityofLubeck

SepticShockassociatedRhabdomyolisis

4treatments/80h

30.000ug/L <1000ug/L-  IL6reductionandinflammatorystateimprovement

PoliclinicoSanMarco,Zingonia

RhabdomyolisiswithARFafterlaparoscopicsleevegastrectomy

1treatment/24h 52.800ng/dl 8.862ng/dl-  CPKReduction(52%)-  RenalFunctionImprovement

VillaSofia,Palermo

TraumaAssociatedRhabodmyolisis–Case

series1treatment/24h

averagevalue>10.000ng/

ml

Averagereduction:58

%

-  CytosorbinHP-ARFprevention,noneedforCRRT

BaggiovaraHospital,Modena

MassiveRhabdomyolisisdueto

cocaineoverdose

3treatments/63h

198.175ng/ml

36.025ng/ml-  Diuresisprogressive

recovery

CattinaraHospital,Trieste

MassiveRhabdomyolisisdueto

cocaineoverdose2treatments/48h

>63.000ng/ml

11.570ng/ml-  CKReduction-  RenalfunctionRecovery

ChietiHospital,Chieti

CrushinducedRhabdomyolisis

2treatments/48h

>20.000ng/ml

1.480ng/mlStabilizationofallparameters

RietiHospital,Rieti

CrushinducedRhabdomyolisis

OnAverage3treatments

>12.000ng/ml

physiologicalvalues

Diuresisandrenalindicesrecovery

RhabdomyolysisinducedAKIandCytosorb

•  Acute renal failure is a common complication in rhabdomyolysis, due to themyoglobinnephrotoxicity,andmayleadtoirreversiblerenaldamage;

•  It is necessary to identify a proper and effective purification strategy for theremovalofthenephrotoxicmoleculescirculatingintheblood;

•  Adsorptionmaybethebesttechniquetoovercomethelimitsofdialysis;

•  HemoadsorptionwithCytosorbisaneffectiveandrapidmethodfortheremovalofmyoglobinandothermuscleenzymes;

•  The PROJECT NATURE Study is investigating the possibility to improve thetraditionaldialytic efficiency in the reductionofuremicproteinbound toxinsbyhemoadsorbtion.


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Dept. of Nephrology and Dialysis, Research Hospital “Casa … · 2020-02-18 · Bosch X et al....

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