1. David Askenazi MD MSPH pCRRT meeting September 28, 2012
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
0 days to 21+ years
1.3 kg to 200 kg
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

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 ( H20 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
Stage
Serum Creatinine Criteria
UOP 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 Premature Neonate Cardiopulmonary Bypass
ECMO
Cardiopulmonary Bypass
Premature Neonate
Infant with Peri-natal Asphyxia
Sick Infant in NICU
What are the outcomes in those with CRRT
What are the outcomes in those with AKI?
How often does it happen?

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

15. Difference in Survival between infants with AKI and without AKI
Death
N = 26
Crude HR
Adj** HR (95% CI)
Any AKI
No AKI
179 9
Ref 24 17
9.3 (4.1, 21.0)
2.3(0.9, 5.8)
AKI Category
AKI 1 7 3
6.8 (1.8, 25.0)
2.5 (0.6, 9.8)
AKI 2
6.1 (1.6, 22.2)
1.6 (0.4, 6.1)
AKI 3 10 11
12.4 (5.1, 30.1)
2.8 (1.0, 7.9)
**controlled for Gestational age, Birth weight, High frequency ventilation
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. 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
Infants with AKI had increased mortality
33/46 (70%) vs. 10/46 (22%); p < 0.0001)
oliguric patients higher mortality
31/38 (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 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
Variable
AKI
No AKI P
Days in NICU
0.014
Days of Hospitalization
0.005
Days of Mechanical Ventilation
<0.001
Survival to ICU discharge *
31(86)
58(97)
0.099
Selewski , 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 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

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. 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 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 N Survivors Am J Kid Dis, 18:833-837, 2003 36%14 13 12 9 5 4 3 2 1 10
Congen Ht Dz
Metabolic
Multiorg Dysfxn
Sepsis
Liver failure
Malignancy
Congen Neph Synd
Congen Diaph Hernia
HUS
Ht Failure
Obstr Urop
Renal Dyspl
Other
36%
71%
15%
42%
22%
50%
100%
60%
Percentages instead of numbers
Totals: N=85; Survivors=32

28. Children < 10 kg in the ppCRRT Registry
Survivors
N = 36
Non-Survivors
N = 48
p value
Male Gender
21/36 (58%)
30/48 (63%)
0.82
Weight (kg)
5.0
5.2
0.71
Age (days)
255
335
0.68
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 ***
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
Survivor
Non-Survivor P
Mean Airway Pressure
(at CRRT Conclusion) 11 20
<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)
2.4
1.0
0.02
Multiorgan system failure
68%
91%
0.04
PRISM score
(at ICU admit) 16 21
<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
Variable
Adjusted OR
p-value
PRISM II score at CRRT
1.1 (1.0 – 1.2)
0.02
Fluid Overload Groups
      < 10 % vs %
0.9 (0.17 – 4.67)
0.25
      < 10 % vs. > 20 %
4.8 ( )
0.01
UOP CRRT start
0.72 ( )
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!
< 5kg
N = 170
> 5kg
N = 251
Anticoagulation
<0.001
Citrate
76 (45%)
155 (62%)
Heparin
94 (55%)
96 (38%)
Prime
Blood
164 (96.5%)
202 (80%)
Saline
5 (3%)
29 (12%)
Albumin
1 (0.5%)
20 (8%)
Blood Flow *
(ml/kg/min)
12 ( )
6.6 ( )
Daily Effluent Volume*
(ml/hr/1.73m2)
3328
( )
2321
( )
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?

38. VS PD vs. HD vs. CRRT 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 VS
Pediatr Nephrol (2009) 24:37–48

39. Peritoneal dialysis Advantages Disadvantages 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 Disadvantages Highest efficiency
High Effort and Cost
High Acuity
Accomplish Goals in 3 – 4 hours difficult
Daily blood prime – implications on transplant

41. CRRT Advantages Disadvantages 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
Circuit volume > 10-15% patient blood volume
Example
5 kg infant : Blood Volume = 400 cc (80/kg)
Prismalex circuit – M60
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.

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

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

51. Blood Prime GO
Brophy et al. AJKD 2001 51

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 RestartNS

54. Anticoagulation

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

56. Choosing QB 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: ml/min
11-20kg: ml/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

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!