CRRT for NeonatesDavid Askenazi MD MSPH

pCRRT meetingSeptember 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

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

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 ICUA -- 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 MetabolismO -- Overload of Fluids ( H20 retention) -- Pulmonary edema or hypertension

U -- Uremia - Not azotemia which can be secondary to steroids, bleeding -- CNS encephalopathy, vomiting, pericarditisNOT AMNEABLE TO MEDICAL T

HERAPY

Neonatal AKI Definition

Stage Serum Creatinine Criteria UOP criteria1 ↑ SCr of ≥0.3 mg/dl or

↑ SCr to 150-199% of baselineUOP > 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 valueNo Major Congenital Anomalies of the Kidney and Urinary Tract

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

EpidemiologyNeonatal AKI and CRRT

Neonatal AKIECMO

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

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

Koralkar et al…Pediatric Research 2010

No AKIStage 1Stage 2Stage 3

Neonatal AKI in VLBW Infants

18% incidence of AKI

Survival

N = 203

Death

N = 26

Crude HR Adj** HR (95%

CI)

Any AKI

No AKI 179 9 Ref Ref

Any AKI 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 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)

**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

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

• 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

AKI in ELBW infants

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 2011 - Philadelphia

No AKI

AKI

Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia

• 96 consecutive infants at U. of Michigan• AKIN• 38% AKI

No AKIStage 1Stage 2Stage 3Selewski , et al…

abstract presented at CRRT 2012

Neonatal AKI in infants w/ perinatal asphyxia treated w/ hypothermia

Selewski , Askenazi et al… abstract presented at CRRT 2012

Variable AKI No AKI PDays in NICU 15.4 + 9.3 11.0 + 5.9 0.014

Days of Hospitalization

17.3 + 10.8 11.3 + 6.4 0.005

Days of Mechanical Ventilation

9.7 + 5.9 4.8 + 3.7 <0.001

Survival to ICU discharge *

31(86) 58(97) 0.099

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

Incidence of AKI = 71%

No AKIAKI

• 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

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.

Blinder JJ, et al.. J Thorac Cardiovasc Surg. July 2011

Incidence of AKI = 52% NO AKIAKI stage 1AKI stage 2AKI stage 3

Neonatal AKI after Cardio-pulmonary Bypass Surgery

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

Survival by Diagnosis

0

36%71%15%42%22%0

50%

50%50%

100%0

60%

Am J Kid Dis, 18:833-837, 200314

14

13

12

9

5

4

3

2

2

1

1

5

5

10

2

5

2

0

2

0

1

1

1

0

3

Congen Ht DzMetabolic

Multiorg DysfxnSepsis

Liver failureMalignancy

Congen Neph SyndCongen Diaph Hernia

HUSHt Failure

Obstr UropRenal Dyspl

Other

38%

62%

Outcome

Survived

Died

NSurvivors

Children < 10 kg in the ppCRRT Registry

SurvivorsN = 36

Non-SurvivorsN = 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

ppCRRT Data of Infants < 10 kg:

43%

57%

Outcome

SurvivedDied

Askenazi et.al. Journal of Pediatrics 2012 – in press

Smaller infants in ppCRRT have lower survival

<5 kg 5-10 kg <10 kg >10 kg0%

10%

20%

30%

40%

50%

60%

70%

Askenazi et.al. Journal of Pediatrics 2012 – in press

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%) 0.59Inborn Error of Metabolism

13/84 (15%) 8/13 (62%) 5/ 13 (38%) 0.15

hepatic 9/84 (11%) 0/9 (0%) 9 /9 (100%) < 0.01Oncology* 6/84 (7%) 3/6 (50%) 3/6 (50%) 0.73Primary Pulmonary

5/ 84 (6%) 3/5 (60%) 2/5 (40%) 0.44

Renal ** 5/84 (6%) 4/5 (80%) 1/ 5 (20%) 0.09Other *** 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 kgSurvivor Non-

SurvivorP

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

Survival Differences by Fluid Overload in Infants < 10 kg enrolled in ppCRRT

Askenazi et.al. Journal of Pediatrics 2012 – in press

< 10 % 10-20% >20%0

10

20

30

40

50

60

70

Fluid Overload Categories

Perc

ent S

urvi

val

Fluid overload is bad for neonates

Variable Adjusted OR p-valuePRISM II score at CRRT 1.1 (1.0 – 1.2) 0.02Fluid Overload Groups      < 10 % vs. 10-20 % 0.9 (0.17 – 4.67) 0.25      < 10 % vs. > 20 % 4.8 (1.3-17.7) 0.01UOP (ml/kg/hr) @ CRRT start 0.72 (0.53-0.97) 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

N = 170

> 5kg

N = 251Anticoagulation <0.001

Citrate 76 (45%) 155 (62%)Heparin 94 (55%) 96 (38%)

Prime <0.001Blood 164 (96.5%) 202 (80%)Saline 5 (3%) 29 (12%)Albumin 1 (0.5%) 20 (8%)

Blood Flow *(ml/kg/min) 12 (7.9-15.6) 6.6 (4.8-8.8) <0.001

Daily Effluent Volume*(ml/hr/1.73m2)

3328

(2325-4745)

2321

(1614-2895)<0.001

Circuit LIfe 28 (11-67) 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

• 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

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

PRBC

WasteNS Bag

Brophy et al. AJKD 2001

Blood Prime 10 ml / min

Blood Flow = 20 ml / min

GO

10 ml / min

NaHCO3

Calcium Gluconate

PRBC

WasteNS Bag

Brophy et al. AJKD 2001

Blood PrimeNaHCO3

Brophy et al. AJKD 2001

Blood Prime

GO

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!