Transcript Pediatric CRRT: The Prescription

Pediatric CRRT:
The Prescription
Stuart L. Goldstein, MD
Associate Professor of Pediatrics
Baylor College of Medicine
What’s in a CRRT Prescription?
Indication (Why? Who? When?)
 Technical Aspects (What?)

 Fluids
(Symons)
 Anticoagulation (Brophy)
 Access (Hackbarth)

CRRT Delivery (How?)
 Blood
pump flow rates
 Modality
 Priming
 Dose
Why CRRT in AKI?

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Critically ill patient
Advantages
 Slower
blood flows
 Slower UF rates
 UF rates can be prescriptive (versus PD)
 Adjust UF rates with hourly patient intake
 Increased cytokine (bad humors) removal?

Disadvantages
 Increased
cytokine (good humors) removal?
 Non-dialysis personnel with many other bedside
responsibilities required to monitor circuit
When Should CRRT Be Started?

Standard AKI criteria not responsive to
medical therapy OR only preventable with
limiting adequate nutrition
 Uremia
 Hyperkalemia
 Acidosis
 Fluid

Overload
Prevention of worsening fluid overload?
Timing of Pediatric RRT
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No adequate definition for “timing of initiation”
Absence of a generally accepted, validated and
applied AKI definition has impeded the adequate
investigation of this question
The decision to initiate RRT affected by
 Strongly
held physician beliefs
 Patient characteristics
 Organizational characteristics
Retrospective evaluation of 226 children
who received RRT for AKI from 1992-1998
 Pressor use surrogate marker for patient
severity of illness
 Survival defined at PICU discharge
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Retrospective review of all patients who received
CVVH(D) in the Texas Children’s Hospital PICU from
February 1996 through September 1998 (32 months)
Pre-CVVH initiation data:
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Age
Primary disease leading to need for CVVH
Co-morbid diseases
Reason for CVVH
Fluid intake (Fluid In) from PICU admission to CVVH
initiation
Fluid output (Fluid Out) from PICU admission to CVVH
initiation
GFR (Schwartz formula) at CVVH initiation
Percent Fluid Overload Calculation
[
% FO at CVVH initiation =
Fluid In - Fluid Out
ICU Admit Weight
]
* 100%
Fluid In = Total Input from ICU admit to CRRT initiation
Fluid Out = Total Output from ICU admit to CRRT initiation
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22 pt (12 male/10 female) received 23 courses (3028 hrs) of
CVVH (n=10) or CVVHD (n=12) over study period.
Overall survival was 41% (9/22).
Survival in septic patients was 45% (5/11).
PRISM scores at ICU admission and CVVH initiation were 13.5
+/- 5.7 and 15.7 +/- 9.0, respectively (p=NS).
Conditions leading to CVVH (D)
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Sepsis (11)
Cardiogenic shock (4)
Hypovolemic ATN (2)
End Stage Heart Disease (2)
Hepatic necrosis, viral pneumonia, bowel obstruction and End-Stage
Lung Disease (1 each)
Survival curve
demonstrates that
nearly 75% of
deaths occurred
less than 25 days
into the ICU course
0
.8
CumulativeProportionSurviving
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Lesser % FO at CVVH (D)
initiation was associated with
improved outcome (p=0.03)
Lesser % FO at CVVH (D)
initiation was also associated
with improved outcome when
sample was adjusted for
severity of illness (p=0.03;
multiple regression analysis)
4
5
4
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3
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p=
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%FOatCVVHInitiation
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N=113 *p=0.02; **p=0.01
N = 77
Group
All
Subjects
Fluid
Hazard Ratio (95% CI)
Overload
<10%
P
1
0.002
>10%
3.02 (1.50-6.10)
Kaplan-Meier survival estimates, by percentage
fluid overload category
The Evolution of Idea to Practice
Paradigm
Registry
Single center study
Randomized
Trial
Prospective Pediatric CRRT (ppCRRT ) Registry:
Phase 1 Design
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Collect prospective data from 10 pediatric
centers treating 15 to 20 patients annually
(376 patients over 5 years)
Each center follows own institutional practice
 Patient
selection
 Initiation and termination
 Anti-coagulation protocols
 Convection versus diffusion versus
hemodiafiltration
 Fluid composition
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Seven center study from
the ppCRRT Registry
116 patients with MODS
PRISM 2 score used to
assess patient severity of
illness
Survival defined at PICU
discharge
 77% of non-survivors die within 3 weeks
of ICU admission
 Survival rates similar by CRRT modality
(H 57%), (DF 53%), (HD 50%)
 Survival rates similar for patients on: 01 (53%), 2 (54%) or 3+ (39%) pressors
 Survival rates better for patients with:
<20% FO (59%) versus >20% FO (40%) at
CRRT initiation (p<0.001)
The PCRRT Prescription: How?
Blood pump flow rates
 Membranes
 Priming
 Modality
 Dose
 UF rates
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Blood flow rates vary
by patient size
 Mean
5 ml/min/kg
 CRRT clearance not
limited by Qb

50% of ppCRRT
patients received
some convection
Pediatric CRRT Circuit Priming
Heparinized (5000 units/L) for most
patients
 Smaller patients require blood priming to
prevent hypotension/hemodilution

 Circuit
volume > 10-15% patient blood volume
 Packed RBCs
Citrated – low ionized calcium
 Acid load
 Potassium load

Bradykinin Release Syndrome
Mucosal congestion, bronchospasm,
hypotension at start of CRRT
 Resolves with discontinuation of CRRT
 Thought to be related to bradykinin release
when patient’s blood contacts hemofilter

 Most

common with AN-69 membranes
Exquisitely pH sensitive
Technique Modifications to Prevent
Bradykinin Release Syndrome

Buffered system
 THAM,

CaCl, NaBicarb to PRBCs
Bypass system
 prime
circuit with saline, run PRBCs into
patient on venous return line

Recirculation system
 recirculate
blood prime against dialysate
PRBC
Waste
Normalize pH
D
Recirculation
Plan:
Qb 200ml/min
Qd ~40ml/min
Time 7.5 min
Normalize K+
Waste
Does Modality Make A Difference?
Equal clearance of smaller molecules
 Middle and large molecule clearance
enhanced by convection
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Membrane Selectivity
IgG 150,000 D
Creatinine 113 D
Urea 60 D
Vit. B12
Glucose 180 D 1,355 D
2-M
11,800 D
Albumin
66,000 D
Courtesy of J. Symons
Clearance: Convection vs. Diffusion
Solute Molecular Weight and Clearance
Solute (MW)
Sieving Coefficient
Diffusion Coefficient
Urea (60)
1.01 ± 0.05
1.01 ± 0.07
Creatinine (113)
1.00 ± 0.09
1.01 ± 0.06
Uric Acid (168)
1.01 ± 0.04
0.97 ± 0.04*
Vancomycin (1448)
0.84 ± 0.10
0.74 ± 0.04**
*P<0.05 vs sieving coefficient
**P<0.01 vs sieving coefficient
Pediatric Sepsis
CRRT Modalities
22%
26%
52%
CVVH
CVVHD
Flores FX et al: CRRT 2006 abstract
CVVHDF
Indications to Initiate CRRT in
Pediatric Sepsis Patients
8%
54%
38%
Fluid/Electrolytes combined
Fluid overload only
Electrolyte abnormalities only
Flores FX et al: CRRT 2006 abstract
ppCRRT Pediatric Sepsis
Outcome Data
Clinical Variables
Survivors
Non-Survivors
P Value
Age (yrs)
9.010.93
8.071.04
0.50
Initial PRISM 2 Score
14.081.25
171.36
0.07
PRISM 2 Score at CRRT
15.93±1.15
19.25±1.25
0.05
Initial Paw
19.271.59
20.891.69
0.40
FO at CRRT (%)
15.453.85
28.134.33
<0.05
GFR
30.433.25
29.823.17
0.96
CVP (cm H20)
16.371.26
17.871.32
0.41
Number of Pressors
1.580.15
1.880.17
0.19
Time ICU to CRRT (days)
4.732.46
10.602.70
0.11
CRRT duration (days)
9.55.30
19.256.03
0.26
50570.876931.300
44749.87800.92
0.57
2217.01±60.50
2650.56±174.9
<0.05
10.841.27
19.721.30
<0.05
UF volume (ml)
Clearance (ml/hr/1.73 m2)
Paw at end CRRT
ppCRRT Pediatric Sepsis Outcome
Data
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57/102 (56%) pts survived.
Ventilated pts had similar survival rate as nonventilated pts (53% vs. 68%, p=0.1).
There was no significant difference in the
survival rate among CRRT modalities.
Tendency toward better survival with
convective therapies
Flores FX et al: CRRT 2006 abstract
Survival Based on CRRT Modality?

Confounded
 Center
70%
67%
64%
60%
 Timing
of initiation
 Sepsis definition not
standardized
47%
50%
CVVH
CVVHDF
40%
CVVHD
30%
20%
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Suggestive
10 %
0%
 If
all else equal, why
not convect?
Flores FX et al: CRRT 2006 abstract
p=0.19
Dialysate/ Ultrafiltration Rates
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The UF rate/plasma flow rate [=BFRx(1-HCT)]
ratio should < 0.35-0.4 in order to avoid filter
clotting (Golper AJKD 6: 373-386,1985)

Dialysate flow rates ranging from 20-30
ml/min/m2 (~2000ml/1.72m2/hr) are usually
adequate (experiential but consistent with adult
data)

Median survival
 Group
1 (19 days)
 Group 2 (33 days)
 Group 3 (46 days)

Groups 2 and 3 with
longer survival than
Group 1
Minimum UF rates > 35 ml/kg/hr
 Translates to approximately
2000ml/1.73m2/hour for children

Dose: Pediatric CRRT
No published data to suggest an adequate
or optimal CRRT dose in children
 Small molecule clearance and electrolyte
homeostasis is generally easy to achieve
 Is more better?

 Nutrition
balance (what are we removing that
we’d like to leave behind?)