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Periopera(ve
AcuteKidneyInjury
Biomarkers,Physicians,andtheSurgicalAbdomen
Dr.AndrewFergusonDepartmentofAnaesthe?cs&IntensiveCareMedicine
CraigavonAreaHospital
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Disclosures
Noconflictsofinteresttodeclare
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Outline
WhyAKImaJerstous Diagnos?candstagingcriteriaforAKI AKIriskfactorsinperiopera?vepa?ents NovelbiomarkerswhatdotheyofferClinicalchallengesimpactoffluidoverload
Take-homepoints
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Periopera(veAKIisNEVERbenign!
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PredictableandavoidableAKI
shouldneveroccur
Post-opera(veAKIisavoidablein
theelderlyandshouldnotoccur
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Howdowediagnose&stageAKI?
CruzDNetal.Cri?calCare2009;13:211
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NgKP,etal.QMed2011,advanceaccessAugust222011
ThegrimrealityofrealworldAKI
In222non-ICUAKIpa?entsrequiringRRT
29%ofpa?entsdiedwithin30days
37.6%diedwithin90days
51.4%diedwithinoneyear
34.9%ofsurvivorsRRTdependentat1year55%ofsurvivorsoffRRTby90dhadeGFR
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AllgradesofAKImaSer!
CruzDN,etal.Cri?calCare2009;13:211
RicciZ,etal.KidneyInterna?onal2008;73:538-546
ClechC,etal.CritCare2011;15:R128
MandelbaumT,etal.CritCareMed2011;39:Epubaheadofprint
AKIN
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coringPeriopera(veAKIRisk
Age>56years Malegender Ac?veCHF Ascites Hypertension MildtomoderateCKD DiabetestreatedwithOHAorinsulin Emergencysurgery Intra-peritonealsurgery
Riskfactors Hazardra(o0-2 1
3 3.1
4 8.5
5 15.4
6 46.2
KheterpalS,etal.Anesthesiology2009;110:505-515
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Incidence-emergencysurgery
N=61,meanage75,unpublishedauditdata
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Incidenceelec(vesurgery
tudy Popula(on AKIdefini(on AKIincidence
Thakar1Retrospec(ve504pa?entsgastricbypass
>50%riseincrea?nineor
needforHD 8.5%
Kheterpal2Prospec(ve,observa?onalmajornon-cardiacsurgery15,102pa?ents
crea?nineclearance>80ml/min
Crea?nineclearance
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Earlydiagnosisthecrea(nineissue
Varia?onwithmusclemass&ageetc. Insensi?vetorapidchangesinrenalfunc?on Insensi?vetolesserdegreesofdysfunc?on FrequentlyabsentbaselineLag?melostopportunityfortherapy
Alteredbyfluidshi^sandfluidbalance1
Posi?vebalancecanhideAKI1LiuKD,etal.CritCareMed2011;39:Epubaheadofprint(uly2011)
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Biomarkerstherenalcrystalball?
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Renalbiomarkercandidates
Kidneyinjurymolecule1(KIM-1) Cysta?nC Interleukin18(IL-18) Andothers
Neutrophilgela(nase-associatedlipocalinNGAL)
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NGAL-whatisit?
25kDaproteinup-regulatedinrenalinjury PresentinurineandplasmainAKI Levelrisesasearlyas2hoursaercellinjury Fallswithsuccessfultherapy(animalmodels)
PredictsAKI
PredictspooroutcomesRRT/death)
Allowsmonitoringoftherapy
HaaseM,etal.CurrOpinCritCare2010;16:526-532
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Timehours)03-62448
NGAL
KIM-1
Cysta(nC
Crea(nine
McIlroyDR,WagenerG,LeeHT.Anesthesiology2010;112:998-1004
Biomarker(me-course
Therapeu(cwindow
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0
2
4
6
8
10
12
14
1618
20
NGAL-/
Creat-
NGAL+/
Creat-
NGAL-/
Creat+
NGAL+/
Creat+
RRT
Hospdeath
Composite
NGALandsubclinicalAKI
NGALriseonly=similaroutcomestoNGAL&crea?ninerise Retrospec?vepooleddesignHaaseM,etal.AmCollCardiol2011;57:1752-1761
%
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Biomarkers-unresolvedissues
Bedsidevs.laboratorytes?ng Lackofreal-worldassayvalida?on Timing/frequencyoftes?nguncertain Lackofevidenceforwhatsbesttodonext Impactoftes?ngonoutcomesunclear
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Challengesinperiopera(veAKI
Needssurgery
NOW!
Canwekeepup?
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AKITriggers&Perpetuators
AKIHypotension
Hypovolaemia
Drugs,toxins,
contrast
Cardiacdysfunc(on
Tissueoedema
Abdominalhypertension
Microvasculardysfunc(on
epsis
Fluidoverload
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AKIhurtsotherorgansystems
GramsME,RabbH.KidneyInterna?onal2011;advanceonlinepublica?on,3August2011
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Generalmanagement
Op?misehaemodynamics
Appropriatefluidchallenges+/-inotrope/pressor(dobutamine/dopamine)
Stopnephrotoxins&adjustdrugdoses Treatunderlyingsepsis/obstruc?on Physiologicalsurveillance/management
EscalatetoHDU/ICUCRRT NephrologyconsultIHD
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Problemareas-fluidoverload
Fluidsdonotreversevasodilatoryhypotension Associatedwithpooroutcomes Causesorgan/?ssueoedema Causesvenousconges?on Worsens?ssueperfusion Intraabdominalhypertension
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Fluidoverload&adverseoutcomePopula(on N Design Results
ARD+AKI1 306 Retrospec(veanalysisofRCT trongassocia(on+vebalanceandmortality
Sep?cshock2 778 Retrospec?veanalysisofRCT+vebalancecorrelatedwith
increasedmortality
AKI3 297 Prospec(vecohortMore+vebalanceassociated
withmortality
AKI4 618 Prospec(vecohortMore+vebalanceassociated
withmortality
ICU5 1,120 Prospec?vecohortMore+vebalanceassociated
withmortality
ARDS6 1,000 RCT Conserva?vebalance=shorterven?la?on?me
Pancrea??s7 247 Prospec?vecohortMore+vebalanceassociated
withincreasedorganfailures
1GramsME,etal.ClinAmSocNephrol2011;6:966-9732BoydH,etal.CritCareMed2011;39:259-265
3SutherlandSM,etal.AmKidDis2010;55:316-325
4Bouchard,etal.KidneyInt2009;76:422-4275PayenD,etal.CritCare2008;12:R74
6WiedemannHP,etal.NEnglMed2006;354:2564-25757de-MadariaE,etal.AmGastroenterol2011.Epub30/08/2011
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Fluidoverloadcauses(ssueoedema
Cerebral Alteredmentalstatus
Myocardial Arrhythmia,diastolic/systolicdysfunc?on
Pulmonary Impairedgasexchange,increasedwork
Hepa(c Cholestasis
Renal DecreasedRBF&GFR,venousconges?on
Gut Ileus,anastomo?cbreakdownTissue Poorhealing,pressureulcers,infec?ons
ProwleR,etal.NatRevNephrol2010;6:107-115
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Fluidoverloadworsens(ssueperfusion
Sheddingofendothelialglycocalyx
Triggeredbyhypervolaemia(ANP)&inflamma?on1 Lossofvascularintegrity=>leak Leukocyte/plateletadhesion=>microthrombi
1BrueggerD,etal.BasicResCardiol2011;19 thulyOnlineFirst
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Microvascularresponsestofluid
Differsfromthemacro-haemodynamicresponse ImprovementinCOandBPdonotguaranteeimprovementinmicrovascularperfusion
Posi?vemicrovascularresponsetofluidbolusdiminishessignificantlyover?me
PoJecher,etal.IntensiveCareMed2010;36:1874
Ospina-TasconG,etal.IntensiveCareMed2010;36:949-955
HarroisA,etal.CurrOpinCritCare2011;17:303-307
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Intra-abdominalhypertension
NormalIntra-AbdominalPressure75mmHg
APP=Meanarterialpressure(MAP)IAP Renalfiltra?ongradient=MAP2*IAP
DecreasedRBF,increasedvenouspressures
Impairedgutbloodflow&guttransloca?on IAP>20+organfailure=compartmentsyndrome
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owhatshouldwedo?
THINKbeforefluidsandMONITORaer Earlyfluidresuscita?onisappropriate Usuallyleadstoearlyposi?vebalance Maketheswitch
Evenbalanceby48hours,nega?vebeyondthisDiure?csorUFEarliermovetoinotropes/pressors
Makeitpartofdailyprac?ce
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Take-homepoints
AnydegreeofAKI=worseoutcome Riskrecogni?onandtailoredjourney
Morehaemodynamicop?misa?on
EarlierrecoursetoHDU/ICU Biomarkers=earlierinterven?on Fluid?mingandbalancearecri?cal Renalrescuebundles
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Poisonisineverything,
andnothingiswithoutpoison.
Thedosagemakesiteitherapoisonoraremedy
PhilippusAureolusTheophrastusBombastusvonHohenheim
Paracelsus(1493-1541)
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