Presentation on theme: "David Askenazi MD MSPH pCRRT meeting September 28, 2012"— Presentation transcript:
1 David Askenazi MD MSPH pCRRT meeting September 28, 2012 CRRT for NeonatesDavid Askenazi MD MSPHpCRRT meetingSeptember 28, 2012
2 Transparency…. I am on the speaker’s bureau for Gambro Will not be discussing specific differences of CRRT machinesI will be talking about non-FDA indications for DevicesNo CRRT devices are approved for < 20 kg.
3 Educational Objectives Acute kidney injury and CRRT epidemiologyIndications for RRT in childrenType of RRT – PD vs. HD vs. CRRTPrescription of CRRT for pediatric patientsVascular accessPriming the machineAnticoagulationBlood flow ratesClearanceNet ultrafiltration goals
4 Children are not small adults Different Sizes, and Shapes0 days to 21+ years1.3 kg to 200 kgNot presentDiabetesOlder ageAtherosclerotic diseaseHypertensionVolume of patientsPresentSize/Access variationLess frequent than adults/less experienceMachinery is adapted (not made) for pediatrics
5 Small Children are not Big Children Blood PrimesAccessMachines are Really not designed for small childrenNeed high blood flow /kgNeed high clearances for citrate clearanceThermic Control is criticalNot FDA approved for small children
6 “Just pull off the sticker” “Explain it to the family”
7 Indications for RRT in the ICU A -- Alkalosis or Acidosis ( metabolic)E -- Electrolyte disturbances-- Hyperkalemia -- hypocalcemia-- Hypernatremia -- hypercalcemia-- Hyperphosphatemia -- hyperuricemiaI -- Intoxication with a drug that can be dialyzedI – Inborn Error of MetabolismO -- Overload of Fluids ( H20 retention)-- Pulmonary edema or hypertensionU -- Uremia - Not azotemia which can be secondary to steroids, bleeding-- CNS encephalopathy, vomiting, pericarditisNOT AMNEABLE TO MEDICAL THERAPY
8 Neonatal AKI Definition StageSerum Creatinine CriteriaUOP criteria1↑ SCr of ≥0.3 mg/dl or↑ SCr to % of baselineUOP > 0.5 cc/kg/hr and≤ 1 cc/kg/hr2↑ SCr to 200%-299% x baselineUOP > 0.1 cc/kg/hr and≤ 0.5 cc/kg/hr3↑ SCr to ≥ 300% of baseline or SCr ≥ 2.5 mg/dl orReceipt of dialysisUOP ≤ 0.1 cc/kg/hrBaseline SCr will be defined as the lowest previous SCr valueNo Major Congenital Anomalies of the Kidney and Urinary Tract
9 Challenges to SCr Based Definitions SCr is a surrogate of FUNCTION not INJURY25-50% functional loss is needed to for SCr changes to occurSCr is affected by medications, billirubin and muscle massSCr rises in Pre-Renal Azotemia – Is that AKI?
10 Challenges to SCr based definitions in neonates Normal Creatinine levels x gestational ageGallini F: Pediatric Nephrology 2000 (15);
12 Neonatal AKI Premature Neonate Cardiopulmonary Bypass ECMOCardiopulmonary BypassPremature NeonateInfant with Peri-natal AsphyxiaSick Infant in NICUWhat are the outcomes in those with CRRTWhat are the outcomes in those with AKI?How often does it happen?
13 Neonatal AKI in VLBW Infants Prospective 18 month study at UABNeonates with BW ≤ 1500 gramsCategorical SCr based AKI definitonclinically-indicated measurements andremnant samples – 10 mcl of serum using Mass SpecNo UOP criteria usedKoralkar, Askenazi et al…Pediatric Research 2010
14 Neonatal AKI in VLBW Infants 18% incidence of AKIKoralkar et al…Pediatric Research 2010
15 Difference in Survival between infants with AKI and without AKI DeathN = 26Crude HRAdj** HR (95% CI)Any AKINo AKI1799Ref24179.3 (4.1, 21.0)2.3(0.9, 5.8)AKI CategoryAKI 1736.8 (1.8, 25.0)2.5 (0.6, 9.8)AKI 26.1 (1.6, 22.2)1.6 (0.4, 6.1)AKI 3101112.4 (5.1, 30.1)2.8 (1.0, 7.9)**controlled for Gestational age, Birth weight, High frequency ventilationKoralkar et al…Pediatric Research 2010
16 AKI in ELBW infants 472 ELBW Neonates at Case Western University AKI DefinitionSCr ≥ 1.5 mg/dl or UOP < 1 ml/kg/hr\12.5 % Incidence of AKIViswanathan et al. Ped Nephrology 2012
17 AKI in ELBW infants 472 ELBW Neonates at Case Western University AKI DefinitionSCr ≥ 1.5 mg/dl or UOP < 1 ml/kg/hr12.5 % Incidence of AKIInfants with AKI had increased mortality33/46 (70%) vs. 10/46 (22%); p < 0.0001)oliguric patients higher mortality31/38 (81%) vs. 2/8 (25%), p = 0.003.Viswanathan et al. Ped Nephrology 2012
18 Neonatal AKI in sick near-term/term infants admitted to level 2 and 3 NICU 58 Neonates admitted to Level 2 or 3 NICUNo congenital anomalies of the kidneyBirth weight > 2000 grams5 minute Apgar ≤ 7SCr criteria only16% Incidence of AKIAskenazi et. al. Abstract at ASN Philadelphia
19 Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia 96 consecutive infants at U. of MichiganAKIN38% AKISelewski , et al… abstract presented at CRRT 2012
20 Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia VariableAKINo AKIPDays in NICU0.014Days of Hospitalization0.005Days of Mechanical Ventilation<0.001Survival to ICU discharge *31(86)58(97)0.099Selewski , Askenazi et al… abstract presented at CRRT 2012
21 Neonatal AKI in infants with CDH on ECMO Infants with congenital diaphragmatic hernia on ECMO (retrospective study)Gadepalli SK, Selewski DT et. al. J Pediatr Surg. Apr 2011
22 Neonatal AKI in infants with CDH on ECMO Patients with stage RIFLE “failure”Increased time on ECMODecreased ventilator free daysSurvival (p< 0.001)AKI = 27%No AKI = 80%Gadepalli SK, Selewski DT et. al. J Pediatr Surg. Apr 2011
23 Neonatal AKI after Cardio-pulmonary Bypass Surgery Retrospective chart review of 430 infants<90 days, (median age 7 days) with CHD.AKI was defined using a modified AKIN definitionurine output criteria includedBlinder JJ, et al.. J Thorac Cardiovasc Surg Jul 26.
24 Neonatal AKI after Cardio-pulmonary Bypass Surgery Blinder JJ, et al.. J Thorac Cardiovasc Surg. July 2011
25 Neonatal AKI after Cardio-pulmonary Bypass Surgery AKI (all stages) - Longer ICU stayAKI stages 2 and 3Increased mechanical ventilationIncreased post-operative inotropic therapy.AKI was associated with higher mortality27/225 (12%) vs. 6/205 (3%) P <0.001Stage 2 OR for death = 5.1(95% CI =1.7 – 15.2; p= 0.004)Stage 3 OR for death = 9.5(95% CI = 2.9 – 30.7; p=Blinder JJ, et al.. J Thorac Cardiovasc Surg.
27 Survival by Diagnosis N Survivors Am J Kid Dis, 18:833-837, 2003 36% 14131295432110Congen Ht DzMetabolicMultiorg DysfxnSepsisLiver failureMalignancyCongen Neph SyndCongen Diaph HerniaHUSHt FailureObstr UropRenal DysplOther36%71%15%42%22%50%100%60%Percentages instead of numbersTotals: N=85; Survivors=32
28 Children < 10 kg in the ppCRRT Registry SurvivorsN = 36Non-SurvivorsN = 48p valueMale Gender21/36 (58%)30/48 (63%)0.82Weight (kg)5.05.20.71Age (days)2553350.68Askenazi et.al. Journal of Pediatrics 2012 – in press
29 ppCRRT Data of Infants < 10 kg: Askenazi et.al. Journal of Pediatrics 2012 – in press
30 Smaller infants in ppCRRT have lower survival Askenazi et.al. Journal of Pediatrics 2012 – in press
31 Children < 10 kg in the ppCRRT Registry Primary DiagnosisN (%)SurvivorNon- Survivorsp-valueSepsis25 / 84 (30%)9/25 (36%)16/25 (64%)0.37Cardiac Disease16 /84 (19%)6/16 (38%)10/16 (62%)0.59Inborn Error of Metabolism13/84 (15%)8/13 (62%)5/ 13 (38%)0.15hepatic9/84 (11%)0/9 (0%)9 /9 (100%)< 0.01Oncology*6/84 (7%)3/6 (50%)0.73Primary Pulmonary5/ 84 (6%)3/5 (60%)2/5 (40%)0.44Renal **5/84 (6%)4/5 (80%)1/ 5 (20%)0.09Other ***3/5 (75%)0.19* (3 neuroblastoma, 2 ALL, one hemophagocytic syndrome)** (ARPKD, cortical necrosis, unknown \CKD, renal agenesis, congenital nephrotic*** (2 nephrotoxin , one congential diaphrmatic hernia, one omenn’s syndrome s/p bmt, one censored)
32 ppCRRT Data of Infants < 10 kg SurvivorNon-SurvivorPMean Airway Pressure(at CRRT Conclusion)1120<0.001Pressor Dependency(throughout CRRT)36%69%<0.01GI/Hepatic disease(present at CRRT start)8%31%0.01Urine output (ml/kg/hr)(at CRRT start)2.41.00.02Multiorgan system failure68%91%0.04PRISM score(at ICU admit)1621<0.05Askenazi et.al. Journal of Pediatrics 2012 – in press
33 Survival Differences by Fluid Overload in Infants < 10 kg enrolled in ppCRRT Askenazi et.al. Journal of Pediatrics 2012 – in press
34 Fluid overload is bad for neonates VariableAdjusted ORp-valuePRISM II score at CRRT1.1 (1.0 – 1.2)0.02Fluid Overload Groups < 10 % vs %0.9 (0.17 – 4.67)0.25 < 10 % vs. > 20 %4.8 ( )0.01UOP CRRT start0.72 ( )0.04*66/84 observations used for analysis (40 death vs 26 Survival).variables used in the model include: PRISM 2 score, mean airway pressure (Paw) and urine output at CRRT, % fluid overload (categorically divided by 10% intervals), MODS and Inborn error of metabolism.Askenazi et.al. Journal of Pediatrics 2012 – in press
35 Small children are dialyzed differently! < 5kgN = 170> 5kgN = 251Anticoagulation<0.001Citrate76 (45%)155 (62%)Heparin94 (55%)96 (38%)PrimeBlood164 (96.5%)202 (80%)Saline5 (3%)29 (12%)Albumin1 (0.5%)20 (8%)Blood Flow *(ml/kg/min)12 ( )6.6 ( )Daily Effluent Volume*(ml/hr/1.73m2)3328( )2321( )Circuit LIfe28 (11-67)37 (16-67)0.15Askenazi et.al. Journal of Pediatrics 2012 – in press
38 VS PD vs. HD vs. CRRT Each has advantages & disadvantages Choice is guided byPatient CharacteristicsDisease/SymptomsHemodynamic stabilityGoals of therapyFluid removalElectrolyte correctionBothAvailability, expertise and costVSPediatr Nephrol (2009) 24:37–48
39 Peritoneal dialysis Advantages Disadvantages No blood prime needed Low volume PD initiation soon after catheter insertionPD prescription10 cc /kg dwell10 minute fill / 40 minute / 10 minute drainRelatively low effortDisadvantagesRisk of peritonitisAbdominal disease is contraindicationLow clearances
40 Hemodialysis Advantages Disadvantages Highest efficiency High Effort and CostHigh AcuityAccomplish Goals in 3 – 4 hours difficultDaily blood prime – implications on transplant
41 CRRT Advantages Disadvantages Slow and Steady Less Hemodynamic Instability? More physiologicDisadvantagesCostEducation of multiple bedside staff
42 Vascular Access for CRRT Put in the largest and shortest catheter when possibleThe IJ site is preferable (over femoral) when clinical situation allowsA 7 or 8 F catheter may not fit in the femoral vein
46 Added Risk for PRBC prime Packed RBCsHYPOCALCEMIC (I Ca++ = 0.2CitrateHYPERKALEMIC (K+ = 5-12 meq/dl)LYSIS OF CELLSACIDICHigh HCT (70%)Protocols for initiation of CRRT use NaHCO3 and Calcium infusions around the time of initiation
47 Blood Primes Prime directly to the machine then hook up the patient Baby Buffer techniqueGive blood to baby and while you pull baby’s blood to prime circuitDual Prisma Setup for restarts.
52 Neonatal Double CRRT Restart “Cross prime” from active circuit to new circuitOnly good when current circuit functioningNo new blood exposureBlood already equilibrated to patientNeed several more hands
55 Anticoagulation Regional Citrate Systemic Heparin Risk for HypocalcemiaAlkalosisHypernatremiaNewborns have decreased liver functionHigh effluent ratesAntibioticsProteinVitaminscarnatineSystemic HeparinPatient anticoagulatedRisk of bleedingRisk for Heparin-Induced ThrombocytopeniaHUGE issue in premies!
56 Choosing QB for Pediatric CRRT Clearance is Primarily Effluent Dependent on CRRTRemember that clearance rates need to be blood flow dependent when using citrate protocols….The real determinant – the vascular accessTry about 3-5 ml/kg / min0-10 kg: ml/min11-20kg: ml/min21-50kg: ml/min>50kg: ml/min
57 5 kg with fluid overload and oliguria Prescription of RRT for pediatric patientsVascular access – Right IJ – place by surgeonMachinery - Prismaflex with M60 filterPriming the machine (ECV = 25% - BLOOD PRIME)Anticoagulation – citrate regional anticoagulationBlood flow rates – 40 ml/minuteClearance : modes, type and goalsCVVHDF ( will need more than 2000 ml/1.73 m2)Net ultrafiltration goalsTake an additional 10 ml per hour
59 How do we improve renal support in neonates? Timing of RRT?Type of RRT?Blood prime protocolsCurrent technology not designed for neonatesSmaller extracorporeal volumesHigher precisionDedicated to neonates
60 Summary Neonatal AKI is common and is associated with poor outcomes Choice of PD vs. HD vs. CRRT are patient and goal specificCRRT can be an effective therapy for even the smallest patientsThe possibility of a dedicated device for neonates may open further options