neonatal aki, metabolic disorders, and · pdf fileneonatal aki, metabolic disorders, and crrt...
TRANSCRIPT
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NeonatalAKI,MetabolicDisorders,andCRRT
DavidAskenaziM.D.
GeoffreyFlemingM.D.
AmeliaAllsteadt RN
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COI
DavidAskenaziM.D.• SpeakerforAKIfoundation
GeoffreyFlemingM.D.• None
AmeliaAllsteadt RN• None
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Overview
• PrescribingCRRTforNeonates– David• BloodPrimeforNeonatalCRRT- Amelia• InfantwithHyperammonemia - Geoffrey• CRRTandECMO- GeoffreyandAmelia• FutureofCRRTinneonates- David
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Case#1
• 2weekoldtermnewbornHPI:Perinatalasphyxiaassociatedwithplacentalabruptionandchorioamnionitis
• Na132mEq/L,K5.1mEq/L,HCO3- 28mEq/L,BUN40mg/dL,SCr1.8mg/dL
• UOP0.3to0.5ml/kg/hr• Currentlyon½volumefeedingswithbreastmilkwith½volumeTPN
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Case1Questions
• DoesthispatienthaveAKI?• Whatwas/istheetiologyofAKI?• Whatelsewouldyouwanttoknowaboutthisinfant?
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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
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NeonatalAKIECMO
CardiopulmonaryBypass
PrematureNeonate
InfantwithPeri-natalAsphyxia
SickInfantinNICU
Whataretheoutcomesin
thosewithAKI?Howoftendoesithappen?
RiskFactorsForNeonatalAKI?
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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
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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
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SmallerchildreninppCRRT havelowersurvival
0%
10%
20%
30%
40%
50%
60%
70%
<5 kg 5-10 kg <10 kg >10 kg
Askenazietal.JournalofPediatrics2013;162:587-92.
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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.
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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
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Case#1Update
• Theinfantyouhavebeenfollowingisnownearly3weeksoldandtheSerumCreatinineisnow3.2mg/dL
• Hehasdeveloped~20%fluidoverloadwithfeeds/TPNandlowUOP
• HiselectrolytesarenowmoreproblematicwithNa130,K5.5,Phos 7.5mg/dL
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Case#1Update
• ShouldyouinstituteRST?• Whatmode?• IFCRRT,thenwhataccess?• Howdoyouperformthetherapy?
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• 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
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CRRTinbabies
• SmallestinfantinppCRRT registry=1.3kg
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PrescribingCRRTforsmallinfants
TWOTPW
• PrescriptionofCRRTforpediatricpatients– Vascularaccess– BloodPrime– Bloodflowrates– Fluids(CVVHvs.CVVHDvs.CVVHDF)– Ultrafiltrationgoals– Anticoagulation– Filteroptions
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NeonatalCRRTAccess
• AccesssizeisKeytosuccess– Frequentclottingandcircuitdowntimeistimewithouttherapy
• Vesselsize– French~3xdiameterofvesselinmm– Besideultrasoundnearlyuniversallyavailable– SVCisbiggerthanfemoralvein
• Lowresistance– Resistance~8lη/2r4
– So,thebiggestandshortestcathetershouldbebest
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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.
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• FortheIJposition• (ItoA)+(AtoB)– 0.5cm• RequiresCXRconfirmation
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• Inpatientswithcardiaclesions• concernsreuppervesselsneededforfuturehearttransplant• Femoralvesselsmaynotbebigenoughforan8FDLC
– Riskforclots– Riskforfutureinabilitytoperformcatheterizations
• Reportedon6babies– PDfailed– Allhad2singlelumencatheters
• Mostranforover60hours….• Averagecircuitlife55.2hr (doublecircuitlifeforinfants<5kginppCRRT registry
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CRRTPrescription
• Qb– Needaminimumof30-50ml/min
• SomeequipmentwillnotallowQb below50ml/min
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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.
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NeonatalCRRT:TheFilter
• Dependinguponequipmentuseddifferentfiltersavailable.– Wewillnotendorsespecificproducts.
• Someofthesmallerfilters/filtersetshavebeenassociatedwithsignificanthemodynamicreactivityatinitiation.
• Usinglargerfilters/filtersetswillincreaseriskofcomplicationswithbloodprimingcircuits…
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CircuitPrimingforNeonatalCRRT
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WHATISBLOODPRIME?
• AMETHODOFREPLACINGTHEPRIMESALINEINTHEDISPOSABLETUBINGSETWITHDONORREDCELLS
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WHYCONSIDERABLOODPRIME?
• Changesinbloodvolumeandreductionincirculatingredcellmassduringaproceduremaybepoorlytoleratedbythepatient.AddingBloodPrimecanhelpmaintainthepatient’shemodynamicstability
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WhenShouldaBloodPrimeBeConsidered?
• ECV:> 10%ofTBV• ExtracorporealRBCvolume:
“IfthedropoforiginalRBCvolumeisgreaterthan30%orthepatientishemodynamicallyunstable,anemic,oratriskoforganischemia.”
Kim,H.“TherapeuticPediatricApheresis.” JournalofClinical Apheresis 15(2000):129-157
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TBVCalculation
• TBVCalculationExamples
Neonates 100mL/kg
Infantsandsmallchildren 80mL/kg
Olderchildrenandadults 70mL/kg
Note:MDorcenterprotocoldetermineswhichTBVcalculationtouse.
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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
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BloodPrimeConsiderations
• WhencalculatingtheECV,asidefromthevolumeinthedisposabletubingset,considerthevolumeofbloodsamplesdrawnandtheECVofanyadditionalinlinedevices(bloodwarmers).
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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.
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AddedRiskforPRBCprime• Anticipatetheneedforplts,ffp forthosewithhighECV
• ProtocolsforinitiationofCRRTuseneedtokeepinmindthatbloodisacidotic(pH7.0)andhypocalcemic (iCa around0.3)– Reconstitutetheblood– likeECMOfolksdoanduseittoprime
– DialyzetheBloodbeforeyoustart– Incorporatebicarbonateandcalcium– Justdoitandbereadytogivecalciumandbicarbonate– Ifyouhaveacircuitrunningandneedtochange– USETHEBLOODinthecurrentcircuitforthesecondcircuit
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BloodPrimeDiagram
CourtesyofDr.Riley
CRRT
OutletInlet
HDCatheter
Blood
DRAINBAG
Patientblood linesconnected afterblood primecomplete
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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
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PRBC
Waste
NSBag
Brophyetal.AJKD2001
BloodPrime10ml/min
BloodFlow=20ml/min
GO
10ml/min
NaHCO3
CalciumGluconate
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PRBC
Waste
NSBag
Brophyetal.AJKD2001
BloodPrimeNaHCO3
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Brophyetal.AJKD2001
BloodPrime
GO
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BloodPrime:Rinseback
• DONOTRINSEBACKtomaintainthepatientinanisovolemicstateandincellularequilibrium,unlessspecifiedbyMD
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Case2
• 2.8kginfantmalebornattermwhopresentsonDOL4toanoutsidehospitalwithlethargyandcardiovascularcollapse.
• Heisresuscitatedwith60/kgnormalsalineandplacedondopamineforhypotension.
• Hisserumammoniais800umol/L• SerumCreatinineis1.5mg/dL
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Case2
• WhatthresholdofammonialeveltostartRST?• Whatisthegoalforammoniaclearance?• Whatisthebestmethodforachievingthisgoal?
• WhenababyisonRSTforhyperammonemiawhatshouldyoudowiththeSodiumBenzoateandSodiumphenylacetate?(Ammonul®)
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InbornErrorsofMetabolism(IEM)
• MostcommonindicationforRSTisHyperammonemia– UreaCycleDefects– OrganicAcidemias
• Durationofhyperammonemia associatedwithneurodevelopmentaloutcome
• Goalisrapiddetoxification– Getlevelbelow200umol/L
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Toxin(NH4)RemovalProcedures
• Extracorporealtherapies– Peritonealdialysis– CRRT– Hemodialysis
• Currentrecommendations:– Bringdownammoniaasquicklyaspossible– Keepitthereuntilyougetmetaboliccontrol
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CRRTvs IHDforIEM
• IHDhasbeenastandardforsometime.– RapiddetoxificationduetohighQbandQd– Problems
• Hemodynamicstability• Smallinfant• Reboundaftercessation
• CRRThasgainedpopularity– Detoxificationcanbeasrapidifclearancesincreased
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• 21infantswithIEM• Clearancewasall>2000
ml/1.73m2/min• Prior IHDdidnotaffect
outcome• 100%of thenon-survivors
were>10%FO
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• NaPheynylacetate andNaBenzoate arecleared
• HoweverPlasmalevelsmayremainsufficientlyelevatedtoprovide furtherNH4management
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Case3
• Neonatebornat38weeksgestationviaC/S• Pre-nataldiagnosisofcongenitaldiaphragmatichernia
• Cannulated ontoECMOonDOL1becauseofseverehypoxicrespiratoryfailureanpulmonaryhypoplasia
• Scr is1.5onDOL2andrisingwithlowUOPandincreasingfluidoverload
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NeonatalCRRTandECMO
• WhodoessomeformofrenalclearanceonECMO?– Whatdoyoudo?– Howdoyoudoit?
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NeonatalCRRTandECMO
• Anoldconcept– EarlydaysofECMOincludedahemodiafilterin-linetoprovideclearance.
• Twomainmethods– In-linehemodiafilter– UsingastandardCRRTmachineconnectedtothecircuit
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In-LineHemodiafilter
• Shuntoffmainfilter– PostPumpInlet– PrepumpOutlet
• UnregulatedQb• HighTMP
– HighpotentialQuf• QufRegulation
– UsingIVpumps• CVVHDreportedinthissetup
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CRRTMachine+ECMO• Connectionwill
dependuponECMOpump– Centrifugalpreferably
postpump– RollerHeadcanbepre
orpostpump• VeryPositiveaccess
pressuresmayrequirechangingalarmprofileinthemachinetowork
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FutureofCRRTinneonates
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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%
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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%
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Wemustthenacknowledge
• ItsamazingwedoCRRTinbabies….• Evenwiththebestpractices….thisapproachexposesthesmallestchildrentoaddedrisk
BenefitRISK≠
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Wemustthenacknowledge
• ItsamazingwedoCRRTinbabies….• Evenwiththebestpractices….thisapproachexposesthesmallestchildrentoaddedrisk
• Youhavereasontobenervous…• Whataboutthe1-2kgbaby?
Dowejustignorehim/her….?• Ifwebelievethatcriticallyillpatientsdobetterwithrenalsupport…wemuststrivetodobetter?
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HowdoweimproveourabilitytosupportneonateswithAKI?
• TimingofRST?• TypeofRST?• Howdoweprimecircuit?• Currenttechnologynotdesignedforneonates
– Shouldwebedoingsuperdialysis?– Dowehavealternatives?
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Letsuseanewfilter….
• HF-20filter(0.2m2 surfacearea)– Optimizedtubingdiametersforimprovedhemodynamicproperties
• CurrentlyAvailableinEurope• UnitedStates
– Pre-clinicalFDAapproval(Dec2013)– StudybeginsinSummer2014
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• CARPEDIEM:Ronco 2012• About10kiddosinEurope
– Smallest1.1kg
• Dedicatedratherthanadaptedmachine
• 3sets:– 27.2,33.5,41.5mlECV
Letsuseanewmachine…
Courtesyandcommunication fromStefanoPiccaMD.
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Adaptasmallerfilter?
• HF-20filter(0.2m2 surfacearea)– Optimizedtubingdiametersforimprovedhemodynamicproperties
• CurrentlyAvailableinEurope• UnitedStates
– Studybeginsin2015
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• CARPEDIEM:Ronco 2012• About10kiddosinEurope
– Smallest1.1kg
• Dedicatedratherthanadaptedmachine
• 3sets:– 27.2,33.5,41.5mlECV
Letsuseanewmachine…
Courtesyandcommunication fromStefanoPiccaMD.
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NewcastleInfantDialysisand
UltrafiltrationSystem(NIDUS)
Coulthard et.al.PediatricNephrology201429(1873-1881)
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NewcastleInfantDialysisandUltrafiltrationSystem(NIDUS)
• Novelsystem– SingleCatheter– 9ccextracorporealvolume– Drivenbysyringesanduncoupledthebabys bloodflowcapac ity fromrequirementofdialysisfilter
• Promisingresults– Improvedclearanceinpiglets(comparedtoPD)– Descriptionof10babies
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TheAquadex™Pureflow
• FDAapprovedforadultswithHeartfailure– resistanttodiuretics
• Tubingandfiltermakeupabout30ml– Smallervascularlines– Portable– Lesscomplexity,risk,andnursingtime
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Letsadaptamachine
• Aquadex –• FDA-- 2007• Indication
• fluidoverloadnotresponsivetodiuretics
• 33cccircuitvolume• HCTlineoptional
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Let’sadaptamachine
68
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Children’sofAlabama(AbstractCRRT2015)
• 10subjects(5UF;5CVVH)• 51circuits• Nodropsinbloodpressure,plts orhct• Welikeit
– Babieslikeit– Nurseslikeit– Intensivists likeit– Nephrologistlikeit.
• Fullcontroloffluid/electrolytes/wasteproducts• Nomajorcomplications
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StateoftheArtforInfantCRRT:Summary
• CRRTcanbeaneffectivetherapyforeventhesmallestpatients
• Overallsurvivalcomparabletolargerchildren- skewedtoselecteddiagnoses
• NeonateswithmetabolicdisordersorintoxicationsmaybenefitfromCRRTvs IHD
• Multiplechallengesremainonseveralfronts• Thepossibilityofabetterdevicesforneonatesmayopenfurtheroptions
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Tellusaboutyourexperience?
• DoyoudoCRRTonneonates?• Doyouhaveaweightcutoff?• Whereisthetherapydone?NICU?PICU?• Whoisonyourteam?