pediatric crrt: the prescription stuart l. goldstein, md associate professor of pediatrics baylor...
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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 ratesModalityPrimingDose
Why CRRT in AKI?
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 nutritionUremiaHyperkalemiaAcidosisFluid Overload
Prevention of worsening fluid overload?
Timing of Pediatric RRT
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
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: 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 OutICU Admit Weight ] * 100%
Fluid In = Total Input from ICU admit to CRRT initiationFluid Out = Total Output from ICU admit to CRRT initiation
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)
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
Survival Time (days)
Cum
ulat
ive
Pro
port
ion
Sur
vivi
ng
0.4
0.6
0.8
1.0
0 20 40 60 80 100
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)
Mean+SEMean-SE
Mean
OUTCOME
%F
O a
t CV
VH
Initi
atio
n
0
5
10
15
20
25
30
35
40
45
Death Survival
p = 0.03
N=113 *p=0.02; **p=0.01
GroupFluid
OverloadHazard Ratio (95% CI) P
All Subjects
<10% 10.002
>10% 3.02 (1.50-6.10)
N = 77
Kaplan-Meier survival estimates, by percentage fluid overload category
The Evolution of Idea to Practice Paradigm
Single center study
Registry
RandomizedTrial
Prospective Pediatric CRRT (ppCRRT ) Registry: Phase 1 Design
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
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: 0-1 (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
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/hemodilutionCircuit volume > 10-15% patient blood volumePacked 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 hemofilterMost common with AN-69 membranes
Exquisitely pH sensitive
Technique Modifications to Prevent Bradykinin Release Syndrome
Buffered systemTHAM, CaCl, NaBicarb to PRBCs
Bypass systemprime circuit with saline, run PRBCs into
patient on venous return line Recirculation system
recirculate blood prime against dialysate
PRBC Waste
D
Waste
Recirculation Plan:
Qb 200ml/min
Qd ~40ml/min
Time 7.5 min
Normalize pH
Normalize K+
Does Modality Make A Difference?
Equal clearance of smaller molecules Middle and large molecule clearance
enhanced by convection
Creatinine 113 DCreatinine 113 D
Urea 60 DUrea 60 D
Glucose 180 DGlucose 180 DVit. BVit. B1212
1,355 D1,355 D
2-M2-M11,800 D11,800 D
AlbuminAlbumin66,000 D66,000 D
IgG 150,000 DIgG 150,000 D
Membrane Selectivity
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 CVVHDF
Flores FX et al: CRRT 2006 abstract
Indications to Initiate CRRT in Pediatric Sepsis Patients
38% 54%
8%
F luid/Electrolytes com binedF luid overload onlyElectrolyte abnorm alities only
Flores FX et al: CRRT 2006 abstract
<0.052650.56±174.92217.01±60.50Clearance (ml/hr/1.73 m2)
0.0519.25±1.2515.93±1.15PRISM 2 Score at CRRT
<0.0519.721.30 10.841.27 Paw at end CRRT
0.5744749.87800.92 50570.876931.300 UF volume (ml)
0.2619.256.03 9.55.30 CRRT duration (days)
0.1110.602.70 4.732.46 Time ICU to CRRT (days)
0.191.880.17 1.580.15 Number of Pressors
0.4117.871.32 16.371.26 CVP (cm H20)
0.9629.823.17 30.433.25 GFR
<0.0528.134.33 15.453.85 FO at CRRT (%)
0.4020.891.69 19.271.59 Initial Paw
0.07171.36 14.081.25 Initial PRISM 2 Score
0.508.071.04 9.010.93Age (yrs)
P ValueNon-SurvivorsSurvivorsClinical Variables
ppCRRT Pediatric SepsisOutcome Data
ppCRRT Pediatric Sepsis Outcome Data
57/102 (56%) pts survived. Ventilated pts had similar survival rate as non-
ventilated 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 Timing of initiation Sepsis definition not
standardized
Suggestive If all else equal, why
not convect?
67%64%
47%
0%
10%
20%
30%
40%
50%
60%
70%
p=0.19
CVVH
CVVHDF
CVVHD
Flores FX et al: CRRT 2006 abstract
Dialysate/ Ultrafiltration Rates
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?)