1. Pediatric CRRT: The Prescription
Stuart L. Goldstein, MD
Professor of Pediatrics
Baylor College of Medicine

2. What’s in a CRRT Prescription?
Indication (Why? Who? When?)
Technical Aspects (What?)
Nutrition (Maxvold)
Anticoagulation (Brophy)
Access (Bunchman)
CRRT Delivery (How?)
Blood pump flow rates
Modality
Priming
Dose

3. Why CRRT in AKI? Critically ill patient Advantages Disadvantages
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

5. 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?

6. 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

7. 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

9. Percent Fluid Overload Calculation[ ]
Fluid In - Fluid Out
ICU Admit Weight
% FO at CVVH initiation =
* 100%
Fluid In = Total Input from ICU admit to CRRT initiation
Fluid Out = Total Output from ICU admit to CRRT initiation

10. 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)

11. Fluid Overload Thresholds at CRRT Initiation and Mortality
Author
FO Threshold
Outcome
Goldstein
Fluid thresholds not assessed
Gillespie
10%
OR death 3.02 > 10% FO
Foland
10% increment
1.78 OR death for
each 10% FO increase
Goldstein (ppCRRT)
20%
<20% FO: 58% survival
>20% FO: 40% survival
Hayes
OR death 6.1 > 20% FO

12. The Evolution of Idea to Practice Paradigm
Registry
Single center study
Randomized
Trial

13. 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

14. ppCRRT FO Threshold
Sutherland S. for the ppCRRT: AJKD 2010

15. 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

16. 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

17. 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

18. PRBC
Waste

19. D Recirculation Plan: Qb 200ml/min Qd ~40ml/min Time 7.5 min Waste
Normalize pH
Normalize K+
Recirculation Plan:
Qb 200ml/min
Qd ~40ml/min
Time 7.5 min
Waste

20. Does Modality Make A Difference?
Equal clearance of smaller molecules
Middle and large molecule clearance enhanced by convection

22. Membrane Selectivity Courtesy of J. Symons IgG 150,000 D
Albumin
66,000 D
Creatinine 113 D
Urea 60 D
Glucose 180 D
2-M
11,800 D
Vit. B12
1,355 D
Courtesy of J. Symons

23. Clearance: Convection vs. Diffusion

24. Solute Molecular Weight and Clearance
Solute (MW) Sieving Coefficient Diffusion Coefficient
Urea (60) 1.01 ± ± 0.07
Creatinine (113) 1.00 ± ± 0.06
Uric Acid (168) 1.01 ± ± 0.04*
Vancomycin (1448) 0.84 ± ± 0.04**
*P<0.05 vs sieving coefficient **P<0.01 vs sieving coefficient

25. Flores FX et al: CRRT 2006 abstract

26. 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

27. Survival Based on CRRT Modality?
Confounded
Center
Timing of initiation
Sepsis definition not standardized
Suggestive
If all else equal, why not convect?
Flores FX et al: CRRT 2006 abstract

28. Dialysate/ Ultrafiltration Rates
The UF rate/plasma flow rate [=BFRx(1-HCT)] ratio should < in order to avoid filter clotting (Golper AJKD 6: ,1985)
Dialysate or effluent flow rates ranging from ml/min/m2 (~2000ml/1.72m2/hr) are usually adequate (experiential but consistent with adult data)

29. 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?)