crrt for neonates
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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 - PowerPoint PPT PresentationTRANSCRIPT
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!