NeonatalAKI,MetabolicDisorders,andCRRT

DavidAskenaziM.D.

GeoffreyFlemingM.D.

AmeliaAllsteadt RN

COI

DavidAskenaziM.D.• SpeakerforAKIfoundation

GeoffreyFlemingM.D.• None

AmeliaAllsteadt RN• None

Overview

• PrescribingCRRTforNeonates– David• BloodPrimeforNeonatalCRRT- Amelia• InfantwithHyperammonemia - Geoffrey• CRRTandECMO- GeoffreyandAmelia• FutureofCRRTinneonates- David

Case#1

• 2weekoldtermnewbornHPI:Perinatalasphyxiaassociatedwithplacentalabruptionandchorioamnionitis

• Na132mEq/L,K5.1mEq/L,HCO3- 28mEq/L,BUN40mg/dL,SCr1.8mg/dL

• UOP0.3to0.5ml/kg/hr• Currentlyon½volumefeedingswithbreastmilkwith½volumeTPN

Case1Questions

• DoesthispatienthaveAKI?• Whatwas/istheetiologyofAKI?• Whatelsewouldyouwanttoknowaboutthisinfant?

NeonatalAKIDefinition

Stage SerumCreatinineCriteria UOPcriteria1 SCr riseby≥0.3 mg/dlw/in48hrs or

SCr riseby≥1.5to1.9Xreference SCrwithin7days

UOP>0.5cc/kg/hrand≤1cc/kg/hr

2SCr rise ≥2to2.9XreferenceSCr

UOP>0.1cc/kg/hrand≤0.5cc/kg/hr

3 SCr rise ≥2to2.9Xreference SCrSCr ≥2.5mg/dlorReceiptofdialysis

UOP≤0.1cc/kg/hr

BaselineSCr willbedefinedasthelowestpreviousSCr value

NeonatalAKIECMO

CardiopulmonaryBypass

PrematureNeonate

InfantwithPeri-natalAsphyxia

SickInfantinNICU

Whataretheoutcomesin

thosewithAKI?Howoftendoesithappen?

RiskFactorsForNeonatalAKI?

Population Incidence MortalityAKI v no AKI

Ref.

VLBW 18% 55% vs. 5% 1

ELBW 12.5% 70% vs. 22% 2

Sick near-term/term

18% 22% vs. 0% 3

Asphyxiated Newborn

38% 14% vs. 2% 4

CPB 25-62% 10-25% vs. 2-8% 5,6,7, 8

ECMO 54% at initiation….Outcomes in those with AKI not good….CRRT and PAS meeting….

NeonatalAKIincidence

References

5Blinder JJ, et al.. J Thorac Cardiovasc Surg 2012. 6Alabbas A et al.. Pediatric Nephrology March 20137 Krawczeski CD et. al. Journal of Pediatrics (158) 6; June 20118 Morgan C, et al 2013 Journal of Pediatrics

1Koralkar, Askenazi et al…Pediatric Research 2010 2Viswanathan et al. Ped Nephrology 20123Askenazi et. al. Pediatric Nephrology Dec 20124Selewski , et al… Journal of Pediatrics Nov 2012

9 Fleming et al. CRRT Abstract 2014

SmallerchildreninppCRRT havelowersurvival

0%

10%

20%

30%

40%

50%

60%

70%

<5 kg 5-10 kg <10 kg >10 kg

Askenazietal.JournalofPediatrics2013;162:587-92.

Smallchildrenaredialyzeddifferently!

< 5kg

N = 170

> 5kg

N = 251Anticoagulation Protocol <0.001

Citrate 76 (45%) 155 (62%)Heparin 94 (55%) 96 (38%)

Prime <0.001

Blood 164 (96.5%) 202 (80%)Saline 5 (3%) 29 (12%)Albumin 1 (0.5%) 20 (8%)

Blood Flow *(ml/kg/min) 12 (7.9-15.6) 6.6 (4.8-8.8) <0.001

Daily Effluent Volume*(ml/hr/1.73m2) 3328 (2325-4745) 2321 (1614-2895) <0.001

Circuit LIfe 28 (11-67) 37 (16-67) 0.15

Askenazietal.JournalofPediatrics2013;162:587-92.

CRRTOutcomesinNewborns

UnderlyingDiagnosis

Survival(%)(n=84)

Sepsis(n=25) 36%

Cardiacdisease(n=16) 38%

InbornerrorofMetabolism (n=13) 62%

Hepaticdisease(n=9) 0%

Oncologicdisease(n=6) 50%

Pulmonary disease(n=5) 60%

Renaldisease(n=5) 80%

Other(n=5) 75%

-Askenazi DJ, et. al.. Continuous Renal Replacement Therapy for Children ≤10 kg: A Report from the ppCRRT Registry. J Pediatr. 2012 Oct 23.

UnderlyingDiagnosis

Survival(%)(n=84)

Renaldisease(n=5) 80%

InbornerrorofMetabolism (n=13) 62%

Pulmonary disease(n=5) 60%

Oncologicdisease(n=6) 50%

Cardiacdisease(n=16) 38%

Sepsis(n=25) 36%

Hepaticdisease(n=9) 0%

Other(n=5) 75%

Total cohort (n=84)

- If > 10kg = 64%

Highest survival in - Primary renal diseases- Inborn errors

Lowest Survival in- Liver failure- Sepsis- Cardiac disease

Case#1Update

• Theinfantyouhavebeenfollowingisnownearly3weeksoldandtheSerumCreatinineisnow3.2mg/dL

• Hehasdeveloped~20%fluidoverloadwithfeeds/TPNandlowUOP

• HiselectrolytesarenowmoreproblematicwithNa130,K5.5,Phos 7.5mg/dL

Case#1Update

• ShouldyouinstituteRST?• Whatmode?• IFCRRT,thenwhataccess?• Howdoyouperformthetherapy?

• Hemodialysis,PeritonealDialysis,CRRT– Eachhasadvantages&disadvantages– Choiceisguidedby

• PatientCharacteristics– Disease/Symptoms– Hemodynamicstability

• Goalsoftherapy– Fluid removal– Electrolytecorrection– Toxinremoval

• Availability,expertiseandcost• ESRD?Toxinremoval?AKIwithlikelyrecovery?

RenalSupportOptions

PediatrNephrol(2009)24:37–48

VS

CRRTinbabies

• SmallestinfantinppCRRT registry=1.3kg

PrescribingCRRTforsmallinfants

TWOTPW

• PrescriptionofCRRTforpediatricpatients– Vascularaccess– BloodPrime– Bloodflowrates– Fluids(CVVHvs.CVVHDvs.CVVHDF)– Ultrafiltrationgoals– Anticoagulation– Filteroptions

NeonatalCRRTAccess

• AccesssizeisKeytosuccess– Frequentclottingandcircuitdowntimeistimewithouttherapy

• Vesselsize– French~3xdiameterofvesselinmm– Besideultrasoundnearlyuniversallyavailable– SVCisbiggerthanfemoralvein

• Lowresistance– Resistance~8lη/2r4

– So,thebiggestandshortestcathetershouldbebest

AccessConsiderations

• InternalJugular– Veryaccessible– Largecaliber(SVC)– Greatflows– Lowrecirculationrate– RiskforPneumothorax– Cardiacmonitoringmaytakeprecedence.

• Femoral– Usuallyaccessible– SmallerthanSVC– Flowsmaybediminishedby:

• AbdominalPressures• Patientmovement

– Riskforretroperitonealhemorrhage

– Higherrecirculationrate

•Subclavian:Manyfeelcurrentdouble lumenvascath aretoostifftomaketheturnintotheSVCandIdon’tpersonallyusethem.Although theyareused insomecenters.•Betterforbiggerkidslikely.

• FortheIJposition• (ItoA)+(AtoB)– 0.5cm• RequiresCXRconfirmation

• Inpatientswithcardiaclesions• concernsreuppervesselsneededforfuturehearttransplant• Femoralvesselsmaynotbebigenoughforan8FDLC

– Riskforclots– Riskforfutureinabilitytoperformcatheterizations

• Reportedon6babies– PDfailed– Allhad2singlelumencatheters

• Mostranforover60hours….• Averagecircuitlife55.2hr (doublecircuitlifeforinfants<5kginppCRRT registry

CRRTPrescription

• Qb– Needaminimumof30-50ml/min

• SomeequipmentwillnotallowQb below50ml/min

CRRTPrescription• Clearance• Mode

– Noprovenbenefitofconvectionvs diffusionforsmallmolecules– Someimprovedclearanceof“middlemolecules”inconvection– ManymaychosetousebothinCVVHDFmode– Itappearsthat>20ml/kg/hr isbeneficial,butnofurtherprovendose

response– ForIEM,however,thismaybepushedupdramaticallytoachieverapid

detoxification– Clearanceisoftenmorethanadequateandneedsattentiontodetails

suchas• Phos,Medications,ProteinLoss

– Whenusingcitrateanticoagulation– rememberthatclearanceofcitrateisnecessaryforagivenbloodflow– thusmanyneonatesendupontonsofclearance.

NeonatalCRRT:TheFilter

• Dependinguponequipmentuseddifferentfiltersavailable.– Wewillnotendorsespecificproducts.

• Someofthesmallerfilters/filtersetshavebeenassociatedwithsignificanthemodynamicreactivityatinitiation.

• Usinglargerfilters/filtersetswillincreaseriskofcomplicationswithbloodprimingcircuits…

CircuitPrimingforNeonatalCRRT

WHATISBLOODPRIME?

• AMETHODOFREPLACINGTHEPRIMESALINEINTHEDISPOSABLETUBINGSETWITHDONORREDCELLS

WHYCONSIDERABLOODPRIME?

• Changesinbloodvolumeandreductionincirculatingredcellmassduringaproceduremaybepoorlytoleratedbythepatient.AddingBloodPrimecanhelpmaintainthepatient’shemodynamicstability

WhenShouldaBloodPrimeBeConsidered?

• ECV:> 10%ofTBV• ExtracorporealRBCvolume:

“IfthedropoforiginalRBCvolumeisgreaterthan30%orthepatientishemodynamicallyunstable,anemic,oratriskoforganischemia.”

Kim,H.“TherapeuticPediatricApheresis.” JournalofClinical Apheresis 15(2000):129-157

TBVCalculation

• TBVCalculationExamples

Neonates 100mL/kg

Infantsandsmallchildren 80mL/kg

Olderchildrenandadults 70mL/kg

Note:MDorcenterprotocoldetermineswhichTBVcalculationtouse.

EXTRACORPOREALVOLUME(ECV)CalculateECVasthe%ofpatient’stotalbloodvolume(TBV)

Ifpt wt >10kg,estimateTBV70ml/kg

ECV% =ECV(ml)

Wt(kg)×70(ml/kg) ×100

Ifpt wt <10kg,estimateTBV80ml/kg

ECV% =ECV(ml)

Wt(kg)×70(ml/kg) ×100

IfusingCRRTinlinewithECMO,include theECMOcircuitvolumeaspartofthepatient’stotalbloodvolume

ECV% =ECV(ml)

Wt(kg)×70(ml/kg) + ECMOvolume(ml)×100

BloodPrimeConsiderations

• WhencalculatingtheECV,asidefromthevolumeinthedisposabletubingset,considerthevolumeofbloodsamplesdrawnandtheECVofanyadditionalinlinedevices(bloodwarmers).

AddedRiskforPRBCprime• PackedRBCs

• HYPOCALCEMIC– Citrate

• HYPERKALEMIC– LYSISOFCELLS

• ACIDIC• TherearenoPlts inpackedpRBC’s

– EveryprimeyoustartCRRTyoushouldexpectforyourplts counttodrop

– Example:• 4kginfant(BV=80*kg=320)• HF1000(ECV=160)• Expectadropinplts of33%

• TherearenocoagulationfactorsinpRBC’s– EveryprimeyoustartCRRTyoushouldexpectforyour

coagulationfactortodrop.

AddedRiskforPRBCprime• Anticipatetheneedforplts,ffp forthosewithhighECV

• ProtocolsforinitiationofCRRTuseneedtokeepinmindthatbloodisacidotic(pH7.0)andhypocalcemic (iCa around0.3)– Reconstitutetheblood– likeECMOfolksdoanduseittoprime

– DialyzetheBloodbeforeyoustart– Incorporatebicarbonateandcalcium– Justdoitandbereadytogivecalciumandbicarbonate– Ifyouhaveacircuitrunningandneedtochange– USETHEBLOODinthecurrentcircuitforthesecondcircuit

BloodPrimeDiagram

CourtesyofDr.Riley

CRRT

OutletInlet

HDCatheter

Blood

DRAINBAG

Patientblood linesconnected afterblood primecomplete

HowtoBloodPrimein10EasySteps

• InitiateCRRTwithoutconnectingpatientasfollows:1. AttachaccesslinetoPRBCbagvia3waystopcockorrecirculator2. Attachreturnlinetosalineprimewastebag(nottheeffluent

bag)3. StartQdial at2000mL/hr4. Startbloodpumpflowrateat30mL/hr5. Startwithpatientfluidremovalrateat0ml/hr6. Oncecircuitiscompletelyprimed,changetheQdial to

prescribedflowrate,connectthepatient,andrestartcircuit7. InitiateACD-AandCaCl2regionalanticoagulationatprescribed

rates8. Increasebloodpumprategraduallytoprescribedrate9. Startreplacementfluids(PBP,postfilter)andpatientfluid

removal(UFR)atprescribedrates10. SendSTATpatientandcircuitiCa levels

PRBC

Waste

NSBag

Brophyetal.AJKD2001

BloodPrime10ml/min

BloodFlow=20ml/min

GO

10ml/min

NaHCO3

CalciumGluconate

PRBC

Waste

NSBag

Brophyetal.AJKD2001

BloodPrimeNaHCO3

Brophyetal.AJKD2001

BloodPrime

GO

BloodPrime:Rinseback

• DONOTRINSEBACKtomaintainthepatientinanisovolemicstateandincellularequilibrium,unlessspecifiedbyMD

Case2

• 2.8kginfantmalebornattermwhopresentsonDOL4toanoutsidehospitalwithlethargyandcardiovascularcollapse.

• Heisresuscitatedwith60/kgnormalsalineandplacedondopamineforhypotension.

• Hisserumammoniais800umol/L• SerumCreatinineis1.5mg/dL

Case2

• WhatthresholdofammonialeveltostartRST?• Whatisthegoalforammoniaclearance?• Whatisthebestmethodforachievingthisgoal?

• WhenababyisonRSTforhyperammonemiawhatshouldyoudowiththeSodiumBenzoateandSodiumphenylacetate?(Ammonul®)

InbornErrorsofMetabolism(IEM)

• MostcommonindicationforRSTisHyperammonemia– UreaCycleDefects– OrganicAcidemias

• Durationofhyperammonemia associatedwithneurodevelopmentaloutcome

• Goalisrapiddetoxification– Getlevelbelow200umol/L

Toxin(NH4)RemovalProcedures

• Extracorporealtherapies– Peritonealdialysis– CRRT– Hemodialysis

• Currentrecommendations:– Bringdownammoniaasquicklyaspossible– Keepitthereuntilyougetmetaboliccontrol

CRRTvs IHDforIEM

• IHDhasbeenastandardforsometime.– RapiddetoxificationduetohighQbandQd– Problems

• Hemodynamicstability• Smallinfant• Reboundaftercessation

• CRRThasgainedpopularity– Detoxificationcanbeasrapidifclearancesincreased

• 21infantswithIEM• Clearancewasall>2000

ml/1.73m2/min• Prior IHDdidnotaffect

outcome• 100%of thenon-survivors

were>10%FO

• NaPheynylacetate andNaBenzoate arecleared

• HoweverPlasmalevelsmayremainsufficientlyelevatedtoprovide furtherNH4management

Case3

• Neonatebornat38weeksgestationviaC/S• Pre-nataldiagnosisofcongenitaldiaphragmatichernia

• Cannulated ontoECMOonDOL1becauseofseverehypoxicrespiratoryfailureanpulmonaryhypoplasia

• Scr is1.5onDOL2andrisingwithlowUOPandincreasingfluidoverload

NeonatalCRRTandECMO

• WhodoessomeformofrenalclearanceonECMO?– Whatdoyoudo?– Howdoyoudoit?

NeonatalCRRTandECMO

• Anoldconcept– EarlydaysofECMOincludedahemodiafilterin-linetoprovideclearance.

• Twomainmethods– In-linehemodiafilter– UsingastandardCRRTmachineconnectedtothecircuit

In-LineHemodiafilter

• Shuntoffmainfilter– PostPumpInlet– PrepumpOutlet

• UnregulatedQb• HighTMP

– HighpotentialQuf• QufRegulation

– UsingIVpumps• CVVHDreportedinthissetup

CRRTMachine+ECMO• Connectionwill

dependuponECMOpump– Centrifugalpreferably

postpump– RollerHeadcanbepre

orpostpump• VeryPositiveaccess

pressuresmayrequirechangingalarmprofileinthemachinetowork

FutureofCRRTinneonates

Whatwearedoinghere……?4kginfant

• Bloodvolume=80*kg≈320ml• Bloodflow=50ml/min=(12ml/kg)• Clearanceflowrates=3500ml/1.73m2/hr =400ml/hr• System– HF1000

– BSA1.1m2(5timesinfant’sBSA)– Extracorporealvolume(ECV)=165ml

• %ECV=165/320≈50%

Whatifwedidthattome……70kg

• Bloodvolume=70*kg≈5000ml=5L• Bloodflow=840ml/min=(12ml/kg)• Clearanceflowrates7000ml/hr =100/kg/hr• SystemMEGA-25,000

– BSA8.6m2(5timesBSA)– Extracorporealvolume(ECV)=2.5L

• %ECV=2.5L/5L≈50%

Wemustthenacknowledge

• ItsamazingwedoCRRTinbabies….• Evenwiththebestpractices….thisapproachexposesthesmallestchildrentoaddedrisk

BenefitRISK≠

Wemustthenacknowledge

• ItsamazingwedoCRRTinbabies….• Evenwiththebestpractices….thisapproachexposesthesmallestchildrentoaddedrisk

• Youhavereasontobenervous…• Whataboutthe1-2kgbaby?

Dowejustignorehim/her….?• Ifwebelievethatcriticallyillpatientsdobetterwithrenalsupport…wemuststrivetodobetter?

HowdoweimproveourabilitytosupportneonateswithAKI?

• TimingofRST?• TypeofRST?• Howdoweprimecircuit?• Currenttechnologynotdesignedforneonates

– Shouldwebedoingsuperdialysis?– Dowehavealternatives?

Letsuseanewfilter….

• HF-20filter(0.2m2 surfacearea)– Optimizedtubingdiametersforimprovedhemodynamicproperties

• CurrentlyAvailableinEurope• UnitedStates

– Pre-clinicalFDAapproval(Dec2013)– StudybeginsinSummer2014

• CARPEDIEM:Ronco 2012• About10kiddosinEurope

– Smallest1.1kg

• Dedicatedratherthanadaptedmachine

• 3sets:– 27.2,33.5,41.5mlECV

Letsuseanewmachine…

Courtesyandcommunication fromStefanoPiccaMD.

Adaptasmallerfilter?

• HF-20filter(0.2m2 surfacearea)– Optimizedtubingdiametersforimprovedhemodynamicproperties

• CurrentlyAvailableinEurope• UnitedStates

– Studybeginsin2015

• CARPEDIEM:Ronco 2012• About10kiddosinEurope

– Smallest1.1kg

• Dedicatedratherthanadaptedmachine

• 3sets:– 27.2,33.5,41.5mlECV

Letsuseanewmachine…

Courtesyandcommunication fromStefanoPiccaMD.

NewcastleInfantDialysisand

UltrafiltrationSystem(NIDUS)

Coulthard et.al.PediatricNephrology201429(1873-1881)

NewcastleInfantDialysisandUltrafiltrationSystem(NIDUS)

• Novelsystem– SingleCatheter– 9ccextracorporealvolume– Drivenbysyringesanduncoupledthebabys bloodflowcapac ity fromrequirementofdialysisfilter

• Promisingresults– Improvedclearanceinpiglets(comparedtoPD)– Descriptionof10babies

TheAquadex™Pureflow

• FDAapprovedforadultswithHeartfailure– resistanttodiuretics

• Tubingandfiltermakeupabout30ml– Smallervascularlines– Portable– Lesscomplexity,risk,andnursingtime

Letsadaptamachine

• Aquadex –• FDA-- 2007• Indication

• fluidoverloadnotresponsivetodiuretics

• 33cccircuitvolume• HCTlineoptional

Let’sadaptamachine

68

Children’sofAlabama(AbstractCRRT2015)

• 10subjects(5UF;5CVVH)• 51circuits• Nodropsinbloodpressure,plts orhct• Welikeit

– Babieslikeit– Nurseslikeit– Intensivists likeit– Nephrologistlikeit.

• Fullcontroloffluid/electrolytes/wasteproducts• Nomajorcomplications

StateoftheArtforInfantCRRT:Summary

• CRRTcanbeaneffectivetherapyforeventhesmallestpatients

• Overallsurvivalcomparabletolargerchildren- skewedtoselecteddiagnoses

• NeonateswithmetabolicdisordersorintoxicationsmaybenefitfromCRRTvs IHD

• Multiplechallengesremainonseveralfronts• Thepossibilityofabetterdevicesforneonatesmayopenfurtheroptions

Tellusaboutyourexperience?

• DoyoudoCRRTonneonates?• Doyouhaveaweightcutoff?• Whereisthetherapydone?NICU?PICU?• Whoisonyourteam?