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CRRT for Neonates David Askenazi MD MSPH pCRRT meeting September 28, 2012.

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Presentation on theme: "CRRT for Neonates David Askenazi MD MSPH pCRRT meeting September 28, 2012."— Presentation transcript:

1 CRRT for Neonates David Askenazi MD MSPH pCRRT meeting September 28, 2012

2 Transparency…. I am on the speaker’s bureau for Gambro Will not be discussing specific differences of CRRT machines I will be talking about non-FDA indications for Devices – No CRRT devices are approved for < 20 kg.

3 Educational Objectives Acute kidney injury and CRRT epidemiology Indications for RRT in children Type of RRT – PD vs. HD vs. CRRT Prescription of CRRT for pediatric patients – Vascular access – Priming the machine – Anticoagulation – Blood flow rates – Clearance – Net ultrafiltration goals

4 Children are not small adults Different Sizes, and Shapes  Not present ◦ Diabetes ◦ Older age ◦ Atherosclerotic disease ◦ Hypertension ◦ Volume of patients  Present ◦ Size/Access variation ◦ Less frequent than adults/less experience ◦ Machinery is adapted (not made) for pediatrics  0 days to 21+ years  1.3 kg to 200 kg

5 Small Children are not Big Children Blood Primes Access Machines are Really not designed for small children – Need high blood flow /kg – Need high clearances for citrate clearance Thermic Control is critical Not 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-- hyperuricemia I -- Intoxication with a drug that can be dialyzed I – Inborn Error of Metabolism O -- Overload of Fluids ( H 2 0 retention) -- Pulmonary edema or hypertension U -- Uremia - Not azotemia which can be secondary to steroids, bleeding -- CNS encephalopathy, vomiting, pericarditis NOT AMNEABLE TO MEDICAL THERAPY

8 Neonatal AKI Definition StageSerum Creatinine CriteriaUOP criteria 1 ↑ SCr of ≥0.3 mg/dl or ↑ SCr to % of baseline UOP > 0.5 cc/kg/hr and ≤ 1 cc/kg/hr 2↑ SCr to 200%-299% x baseline UOP > 0.1 cc/kg/hr and ≤ 0.5 cc/kg/hr 3 ↑ SCr to ≥ 300% of baseline or SCr ≥ 2.5 mg/dl or Receipt of dialysis UOP ≤ 0.1 cc/kg/hr Baseline SCr will be defined as the lowest previous SCr value No Major Congenital Anomalies of the Kidney and Urinary Tract

9 Challenges to SCr Based Definitions – SCr is a surrogate of FUNCTION not INJURY – 25-50% functional loss is needed to for SCr changes to occur – SCr is affected by medications, billirubin and muscle mass – SCr rises in Pre-Renal Azotemia – Is that AKI?

10 Challenges to SCr based definitions in neonates Normal Creatinine levels x gestational age Gallini F: Pediatric Nephrology 2000 (15);

11 Epidemiology Neonatal AKI and CRRT

12 Neonatal AKI ECMO Cardiopulmonary Bypass Premature Neonate Infant with Peri- natal Asphyxia Sick Infant in NICU What are the outcomes in those with AKI? How often does it happen? What are the outcomes in those with CRRT

13 Neonatal AKI in VLBW Infants Prospective 18 month study at UAB Neonates with BW ≤ 1500 grams Categorical SCr based AKI definiton – clinically-indicated measurements and – remnant samples – 10 mcl of serum using Mass Spec No UOP criteria used Koralkar, Askenazi et al…Pediatric Research 2010

14 Koralkar et al…Pediatric Research 2010 Neonatal AKI in VLBW Infants 18% incidence of AKI

15 Survival N = 203 Death N = 26 Crude HR Adj** HR (95% CI) Any AKI No AKI1799Ref Any AKI (4.1, 21.0)2.3(0.9, 5.8) AKI Category AKI (1.8, 25.0)2.5 (0.6, 9.8) AKI (1.6, 22.2)1.6 (0.4, 6.1) AKI (5.1, 30.1)2.8 (1.0, 7.9) **controlled for Gestational age, Birth weight, High frequency ventilation Difference in Survival between infants with AKI and without AKI Koralkar et al…Pediatric Research 2010

16 AKI in ELBW infants 472 ELBW Neonates at Case Western University AKI Definition – SCr ≥ 1.5 mg/dl or UOP < 1 ml/kg/hr\ 12.5 % Incidence of AKI Viswanathan et al. Ped Nephrology 2012

17 472 ELBW Neonates at Case Western University AKI Definition – SCr ≥ 1.5 mg/dl or UOP < 1 ml/kg/hr 12.5 % Incidence of AKI Infants with AKI had increased mortality – 33/46 (70%) vs. 10/46 (22%); p < ) oliguric patients higher mortality – 31/38 (81%) vs. 2/8 (25%), p = Viswanathan et al. Ped Nephrology 2012 AKI in ELBW infants

18 Neonatal AKI in sick near-term/term infants admitted to level 2 and 3 NICU 58 Neonates admitted to Level 2 or 3 NICU – No congenital anomalies of the kidney – Birth weight > 2000 grams – 5 minute Apgar ≤ 7 SCr criteria only 16% Incidence of AKI Askenazi et. al. Abstract at ASN Philadelphia

19 Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia 96 consecutive infants at U. of Michigan AKIN 38% AKI Selewski, et al… abstract presented at CRRT 2012

20 Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia Selewski, Askenazi et al… abstract presented at CRRT 2012 Variable AKINo AKIP Days in NICU Days of Hospitalization Days of Mechanical Ventilation <0.001 Survival to ICU discharge * 31(86)58(97)0.099

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 Patients with stage RIFLE “failure” – Increased time on ECMO – Decreased ventilator free days – Survival (p< 0.001) AKI = 27% No AKI = 80% Gadepalli SK, Selewski DT et. al. J Pediatr Surg. Apr 2011 Neonatal AKI in infants with CDH on ECMO

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 definition – urine output criteria included Blinder JJ, et al.. J Thorac Cardiovasc Surg Jul 26.

24 Blinder JJ, et al.. J Thorac Cardiovasc Surg. July 2011 Neonatal AKI after Cardio-pulmonary Bypass Surgery

25 AKI (all stages) - Longer ICU stay AKI stages 2 and 3 – Increased mechanical ventilation – Increased post-operative inotropic therapy. AKI was associated with higher mortality – 27/225 (12%) vs. 6/205 (3%) P <0.001 Stage 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.

26 Outcomes Children < 10 kg receiving CRRT

27 Survival by Diagnosis 0 36% 71% 15% 42% 22% 0 50% 100% 0 60% Am J Kid Dis, 18: , Congen Ht Dz Metabolic Multiorg Dysfxn Sepsis Liver failure Malignancy Congen Neph Synd Congen Diaph Hernia HUS Ht Failure Obstr Urop Renal Dyspl Other N Survivors

28 Children < 10 kg in the ppCRRT Registry Survivors N = 36 Non-Survivors N = 48 p value Male Gender21/36 (58%)30/48 (63%)0.82 Weight (kg) Age (days) Askenazi 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 Diagnosis N (%) Survivor Non- Survivors p-value Sepsis 25 / 84 (30%) 9/25 (36%)16/25 (64%)0.37 Cardiac Disease 16 /84 (19%) 6/16 (38%)10/16 (62%)0.59 Inborn Error of Metabolism 13/84 (15%) 8/13 (62%)5/ 13 (38%)0.15 hepatic 9/84 (11%) 0/9 (0%)9 /9 (100%)< 0.01 Oncology* 6/84 (7%) 3/6 (50%) 0.73 Primary Pulmonary 5/ 84 (6%) 3/5 (60%)2/5 (40%)0.44 Renal ** 5/84 (6%) 4/5 (80%)1/ 5 (20%)0.09 Other *** 5/84 (6%) 3/5 (75%)2/5 (40%)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- Survivor P Mean Airway Pressure (at CRRT Conclusion) 1120<0.001 Pressor Dependency (throughout CRRT) 36%69%<0.01 GI/Hepatic disease (present at CRRT start) 8%31%0.01 Urine output (ml/kg/hr) (at CRRT start) Multiorgan system failure 68%91%0.04 PRISM score (at ICU admit) 1621<0.05 Askenazi 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-value PRISM II score at CRRT1.1 (1.0 – 1.2)0.02 Fluid Overload Groups < 10 % vs %0.9 (0.17 – 4.67) %4.8 ( )0.01 UOP 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 (P aw ) 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! < 5kg N = 170 > 5kg N = 251 Anticoagulation<0.001 Citrate76 (45%)155 (62%) Heparin94 (55%)96 (38%) Prime<0.001 Blood164 (96.5%)202 (80%) Saline5 (3%)29 (12%) Albumin1 (0.5%)20 (8%) Blood Flow * (ml/kg/min) 12 ( )6.6 ( )<0.001 Daily Effluent Volume* (ml/hr/1.73m 2 ) 3328 ( ) 2321 ( ) <0.001 Circuit LIfe 28 (11-67)37 (16-67)0.15 Askenazi et.al. Journal of Pediatrics 2012 – in press

36 Prescribing Pediatric CRRT

37 Which is better PD, HD or CRRT? 37

38 Each has advantages & disadvantages Choice is guided by – Patient Characteristics Disease/Symptoms Hemodynamic stability – Goals of therapy Fluid removal Electrolyte correction Both – Availability, expertise and cost PD vs. HD vs. CRRT Pediatr Nephrol (2009) 24:37–48 VS

39 Peritoneal dialysis Advantages – No blood prime needed – Low volume PD initiation soon after catheter insertion – PD prescription 10 cc /kg dwell 10 minute fill / 40 minute / 10 minute drain – Relatively low effort Disadvantages – Risk of peritonitis – Abdominal disease is contraindication – Low clearances

40 Hemodialysis Advantages – Highest efficiency Disadvantages – High Effort and Cost – High Acuity – Accomplish Goals in 3 – 4 hours difficult – Daily blood prime – implications on transplant

41 CRRT Advantages – Slow and Steady – Less Hemodynamic Instability – ? More physiologic Disadvantages – Cost – Education of multiple bedside staff

42 Vascular Access for CRRT Put in the largest and shortest catheter when possible The IJ site is preferable (over femoral) when clinical situation allows A 7 or 8 F catheter may not fit in the femoral vein

43 Blood Prime for CRRT

44 Priming the Circuit for Pediatric CRRT Blood – Small patient, large extracorporeal volume Albumin – Hemodynamic instability Saline – Common default approach Self – Volume loaded renal failure patient

45 Pediatric CRRT Circuit Priming Smaller patients require blood priming to prevent hypotension/hemodilution Smaller patients require blood priming to prevent hypotension/hemodilution – Circuit volume > 10-15% patient blood volume Example Example – 5 kg infant : Blood Volume = 400 cc (80/kg) – Prismalex circuit – M60 extracorporeal volume ≈ 100 ml extracorporeal volume ≈ 100 ml – Therefore 25% extracorporeal volume

46 Added Risk for PRBC prime Packed RBCs HYPOCALCEMIC (I Ca++ = 0.2 – Citrate HYPERKALEMIC (K+ = 5-12 meq/dl) – LYSIS OF CELLS ACIDIC High 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 technique – Give blood to baby and while you pull baby’s blood to prime circuit Dual Prisma Setup for restarts.

48 48

49 PRBC Waste NS Bag Brophy et al. AJKD 2001 Blood Prime 10 ml / min Blood Flow = 20 ml / min GO 10 ml / min NaHCO3 Calcium Gluconate

50 PRBC Waste NS Bag Brophy et al. AJKD 2001 Blood Prime NaHCO3

51 Brophy et al. AJKD 2001 Blood Prime GO

52 Neonatal Double CRRT Restart “Cross prime” from active circuit to new circuit Only good when current circuit functioning No new blood exposure Blood already equilibrated to patient Need several more hands

53 Neonatal Double CRRT Restart NS

54 Anticoagulation

55 Systemic Heparin – Patient anticoagulated Risk of bleeding – Risk for Heparin-Induced Thrombocytopenia – HUGE issue in premies! Regional Citrate – Risk for Hypocalcemia Alkalosis Hypernatremia – Newborns have decreased liver function – High effluent rates Antibiotics Protein Vitamins carnatine

56 Choosing Q B for Pediatric CRRT Clearance is Primarily Effluent Dependent on CRRT Remember that clearance rates need to be blood flow dependent when using citrate protocols…. The real determinant – the vascular access Try about 3-5 ml/kg / min 0-10 kg:30-50ml/min 11-20kg:80-100ml/min 21-50kg: ml/min >50kg: ml/min

57 5 kg with fluid overload and oliguria Prescription of RRT for pediatric patients – Vascular access – Right IJ – place by surgeon – Machinery - Prismaflex with M60 filter – Priming the machine (ECV = 25% - BLOOD PRIME) – Anticoagulation – citrate regional anticoagulation – Blood flow rates – 40 ml/minute – Clearance : modes, type and goals CVVHDF ( will need more than 2000 ml/1.73 m2) – Net ultrafiltration goals Take an additional 10 ml per hour 57

58 Future of Neonatal AKI

59 How do we improve renal support in neonates? Timing of RRT? Type of RRT? Blood prime protocols Current technology not designed for neonates – Smaller extracorporeal volumes – Higher precision – Dedicated 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 specific CRRT can be an effective therapy for even the smallest patients The possibility of a dedicated device for neonates may open further options

61 Thanks!


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