CRRT for Neonates
David Askenazi MD MSPH
pCRRT meeting
September 28, 2012
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.
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
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
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
“Just pull off
the sticker”
“Explain it to
the family”
Indications for RRT in the ICU
A -- Alkalosis or Acidosis ( metabolic)
E -- Electrolyte disturbances
-- Hyperkalemia
-- Hypernatremia
-- Hyperphosphatemia
-- hypocalcemia
-- hypercalcemia
-- 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
Neonatal AKI Definition
Stage
Serum Creatinine Criteria
UOP criteria
1
↑ SCr of ≥0.3 mg/dl or
↑ SCr to 150-199% 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
↑ SCr to ≥ 300% of baseline or
UOP ≤ 0.1 cc/kg/hr
SCr ≥ 2.5 mg/dl or
Receipt of dialysis
Baseline SCr will be defined as the lowest previous SCr value
No Major Congenital Anomalies of the Kidney and Urinary Tract
3
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?
Challenges to SCr based definitions in
neonates
Normal Creatinine levels x gestational age
Gallini F: Pediatric Nephrology 2000 (15); 119-124
Epidemiology
Neonatal AKI and CRRT
Premature
Neonate
Cardiopulmonary
Bypass
ECMO
What are the
outcomes in
those with CRRT
Infant with Perinatal Asphyxia
Neonatal
AKI
How often does
it happen?
Sick Infant in
NICU
What are the
outcomes in
those with AKI?
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
Neonatal AKI in VLBW Infants
18% incidence of
AKI
No AKI
Stage 1
Stage 2
Stage 3
Koralkar et al…Pediatric Research 2010
Difference in Survival between
infants with AKI and without AKI
Survival
Death
Crude HR
Adj** HR (95%
N = 203
N = 26
No AKI
179
9
Any AKI
24
17
7
3
6.8 (1.8, 25.0)
2.5 (0.6, 9.8)
AKI 2
7
3
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)
CI)
Any AKI
AKI Category
AKI 1
Ref
Ref
9.3 (4.1, 21.0) 2.3(0.9, 5.8)
**controlled for Gestational age, Birth weight, High frequency ventilation
Koralkar et al…Pediatric Research 2010
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
No AKI
AKI
Viswanathan et al. Ped Nephrology 2012
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
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
No AKI
AKI
Askenazi et. al. Abstract at ASN 2011 - Philadelphia
Neonatal AKI in infants w/ perinatal
asphyxia treated w/ hypothermia
• 96 consecutive infants at U. of Michigan
• AKIN
• 38% AKI
No AKI
Stage 1
Selewski , et al… abstract
presented at CRRT 2012
Stage 2
Stage 3
Neonatal AKI in infants w/ perinatal
asphyxia treated w/ hypothermia
Variable
Days in NICU
Days of
Hospitalization
Days of
Mechanical
Ventilation
Survival to ICU
discharge *
AKI
15.4 + 9.3
No AKI
11.0 + 5.9
P
0.014
17.3 + 10.8
11.3 + 6.4
0.005
9.7 + 5.9
4.8 + 3.7
<0.001
31(86)
58(97)
0.099
Selewski , Askenazi et al… abstract presented at CRRT 2012
Neonatal AKI in infants with CDH on
ECMO
• Infants with congenital diaphragmatic hernia
on ECMO (retrospective study)
Incidence of AKI = 71%
No AKI
AKI
Gadepalli SK, Selewski DT et. al. J Pediatr Surg. Apr 2011
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
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. 2011 Jul 26.
Neonatal AKI after
Cardio-pulmonary Bypass Surgery
Incidence of AKI = 52%
NO AKI
AKI stage 1
AKI stage 2
AKI stage 3
Blinder JJ, et al.. J Thorac Cardiovasc Surg.
July 2011
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= .0002.
Blinder JJ, et al.. J Thorac Cardiovasc Surg.
Outcomes
Children < 10 kg receiving CRRT
N
Survivors
Survival by Diagnosis
Am J Kid Dis, 18:833-837, 2003
36%
Congen Ht Dz
71%
Metabolic
15%
42%
22%
0
5
HUS
3
1
Ht Failure
1
100%
Obstr Urop
1
1
Renal Dyspl 0
1
60%
Other
Outcome
4
2
50%
0
9
2
Malignancy 0
Congen Diaph Hernia0
12
5
Liver failure
0
50%
13
2
Sepsis
Congen Neph Synd
14
10
Multiorg Dysfxn
50%
14
5
2
38%
2
62%
3
5
Survived
Died
Children < 10 kg in the ppCRRT Registry
Male Gender
Weight (kg)
Age (days)
Survivors Non-Survivors
p
N = 36
N = 48
value
21/36 (58%) 30/48 (63%) 0.82
5.0
5.2
0.71
255
335
0.68
Askenazi et.al. Journal of Pediatrics 2012 – in press
ppCRRT Data of Infants < 10 kg:
Outcome
43%
57%
Survived
Died
Askenazi et.al. Journal of Pediatrics 2012 – in press
Smaller infants in ppCRRT have lower
survival
70%
60%
50%
40%
30%
20%
10%
0%
<5 kg
5-10 kg
<10 kg
>10 kg
Askenazi et.al. Journal of Pediatrics 2012 – in press
Children < 10 kg in the ppCRRT Registry
Primary Diagnosis
N (%)
Survivor
NonSurvivors
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
13/84 (15%)
8/13 (62%)
5/ 13 (38%)
0.15
Metabolism
hepatic
9/84 (11%)
0/9 (0%)
9 /9 (100%)
< 0.01
Oncology*
6/84 (7%)
3/6 (50%)
3/6 (50%)
0.73
Primary
5/ 84 (6%)
3/5 (60%)
2/5 (40%)
0.44
Pulmonary
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)
ppCRRT Data of Infants < 10 kg
11
NonSurvivor
20
<0.001
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
68%
16
91%
21
0.04
<0.05
Survivor
Mean Airway Pressure
(at CRRT Conclusion)
Pressor Dependency
(throughout CRRT)
Multiorgan system failure
PRISM score
(at ICU admit)
P
Askenazi et.al. Journal of Pediatrics 2012 – in press
Survival Differences by Fluid Overload in
Infants < 10 kg enrolled in ppCRRT
Percent Survival
70
60
50
40
30
20
10
0
< 10 %
10-20%
>20%
Fluid Overload Categories
Askenazi et.al. Journal of Pediatrics 2012 – in press
Fluid overload is bad for neonates
Variable
PRISM II score at CRRT
Fluid Overload Groups
< 10 % vs. 10-20 %
< 10 % vs. > 20 %
UOP (ml/kg/hr) @ CRRT start
Adjusted OR
1.1 (1.0 – 1.2)
p-value
0.02
0.9 (0.17 – 4.67)
4.8 (1.3-17.7)
0.72 (0.53-0.97)
0.25
0.01
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
Small children are dialyzed differently!
< 5kg
> 5kg
N = 170
N = 251
Anticoagulation
Citrate
Heparin
<0.001
76 (45%)
94 (55%)
155 (62%)
96 (38%)
Prime
Blood
Saline
Albumin
Blood Flow *
(ml/kg/min)
Daily Effluent Volume*
(ml/hr/1.73m2)
Circuit LIfe
<0.001
164 (96.5%)
5 (3%)
1 (0.5%)
202 (80%)
29 (12%)
20 (8%)
12 (7.9-15.6)
6.6 (4.8-8.8)
3328
2321
<0.001
<0.001
(2325-4745)
28 (11-67)
(1614-2895)
37 (16-67)
0.15
Askenazi et.al. Journal of Pediatrics 2012 – in press
Prescribing Pediatric CRRT
Which is better PD, HD or CRRT?
37
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
Pediatr Nephrol (2009) 24:37–48
VS
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
Hemodialysis
• Advantages
– Highest efficiency
• Disadvantages
– High Effort and Cost
– High Acuity
– Accomplish Goals in 3 – 4 hours difficult
– Daily blood prime – implications on transplant
CRRT
• Advantages
– Slow and Steady
– Less Hemodynamic Instability
– ? More physiologic
• Disadvantages
– Cost
– Education of multiple bedside staff
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
Blood Prime for CRRT
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
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
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
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
10 ml / min 10 ml / min
PRBC
Blood Prime
NaHCO3
Calcium
Gluconate
Brophy et al. AJKD 2001
GO
Waste
NS Bag
Blood Flow = 20 ml / min
Blood Prime
PRBC
NaHCO3
Waste
NS Bag
Brophy et al. AJKD 2001
Blood Prime
GO
Brophy et al. AJKD 2001
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
Neonatal Double CRRT Restart
NS
Anticoagulation
Anticoagulation
• 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
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:
30-50ml/min
• 11-20kg:
80-100ml/min
• 21-50kg:
100-150ml/min
• >50kg:
150-180ml/min
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
Future of Neonatal AKI
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
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
Thanks!