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

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

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

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 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

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

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)

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

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

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

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

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

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

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

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

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

Flores FX et al: CRRT 2006 abstract

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? 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 or effluent flow rates ranging from 20-30 ml/min/m2 (~2000ml/1.72m2/hr) are usually adequate (experiential but consistent with adult data)

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?)