WHEN TO CONSIDER RRT Timothy E Bunchman Founder PCRRT

Fluid vs Solute Fluid over load as an indication is easy for one can measure it Solute is more difficult Elevated K, BUN, Phos, Uric Acid? ? Hypermetabolism Septic child with fever and hemodynamic instablitiy

Renal Replacement Therapy in the PICU: Pediatric Outcome Literature Few pediatric studies (all single center) use a severity of illness measure to evaluate outcomes in pCRRT: Lane noted that mortality was greater after bone marrow transplant who had > 10% fluid overload at the time of HD initiation Faragson 3 found PRISM to be a poor outcome predictor in patients treated with HD Zobel 4 demonstrated that children who received CRRT with worse illness severity by PRISM score had increased mortality 1. Bone Marrow Transplant 13:613-7, Pediatr Nephrol 7:703-7, Child Nephrol Urol 10:14-7, 1990

Renal Replacement Therapy in the PICU Pediatric Literature 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) Goldstein SL et al: Pediatrics 2001 Jun;107(6):

Fluid Overload as a Risk Factor Foland et al, CCM 2004; 32: N=113 *p=0.02; **p=0.01

Gillespie et al, Pediatr Nephrol (2004) 19: Kaplan-Meier survival estimates, by percentage fluid overload category

ppCRRT MODS Data BASELINE DEMOGRAPHICS  157 patients entered (1/1/2001 to 5/31/04)  116 with MODS (2+ organs involved)  Mean age years (2 days to 25.1 years)  Mean weight kg (1.9 to 160 kg)  Median 3 ICU days prior to CRRT initiation  Range 0 to 103 days  67%less than 7 days Goldstein SL et al: Kidney International 2005

ppCRRT MODS Data:116 children (ppCRRT KI 2005 Feb;67(2):653-8 )

So… Now about solute? Is it like Art…when you see something you like it is good or if you know in your heart it needs to happen it should? K Metabolic Acidosis Uremia

Dialysis Dose and Outcome Ronco et al. Lancet 2000; 351: Conclusions: Minimum UF rates should be ~ 35 ml/kg/hr Survivors had lower BUNs than non-survivors prior to commencement of hemofiltration 425 patients Endpoint = survival 15 days after D/C HF 146 UF rate 20ml/kg/hr survival significantly lower in this group compared to the others 139 UF rate 35ml/kg/hr p= UF rate 45ml/kg/hr p=0.0013

KDIGO-Kidney Disease Involving Global Outcomes Kid Int Suppl (2012) 2, 89–115 ….” The optimal timing of dialysis for AKI is not defined. In current practice, the decision to start RRT is based most often on clinical features of volume overload and biochemical features of solute imbalance (azotemia, hyperkalemia, severe acidosis)….

KDIGO-Kidney Disease Involving Global Outcomes Kid Int Suppl (2012) 2, 89–115 PICARD Study analyzed dialysis initiation—as inferred by BUN concentration—in 243 patients from five geographically and ethnically diverse clinical sites. Adjusting for age, hepatic failure, sepsis, thrombocytopenia, and SCr, and stratified by site and initial dialysis modality, initiation of RRT begun at a BUN at higher BUN (> 76 mg/dl [blood urea > 27.1mmol/l]) was associated with an increased risk of death (RR 1.85; 95% CI 1.16–2.96). Yet other studies have refuted that

Unique Situations-CRRT When hemodynamic instability and highly catabolic conditions are present Sepsis Bone Marrow Transplantation Goldstein SL Seminars in Dialysis 2009; 22; Walters et al Pediatr Neph ; 37-38

Stem Cell Transplant: ppCRRT 51 patients in ppCRRT with SCT Mean %FO = %. 45% survival Convection: 17/29 survived (59%) Diffusion: 6/22 (27%), p<0.05 Survival lower in MODS and ventilated patients Flores FX et al: Pediatr Nephrol Apr;23(4):625-30

Prospective Pediatric Study 40 patients with Sepsis/ARF at 4 ppCRRT centers Randomized crossover design 24 hours of CVVH or CVVHD, then crossover 2500 ml/hr/1.73m2 clearance Dialysis/Replacement fluid with [HC03]=35mmol/l Citrate ACG Serum collection at 0,1, 24, 25 and 48 hours TNF-alpha IL-1 beta IL-6, IL- 8, IL-10, IL-18 Six hours of effluent for CK’s for clearance estimation

ppCRRT Sepsis Study 10 patients enrolled to date 6 male, 4 female Mean age years Mean weight kg PELOD Mean = Median = 22 (range 11-42)

ppCRRT [Cytokine] % Change: Convection vs. Diffusion CytokineConvectionDiffusionp TNF-alpha IL-1 beta IL IL IL IL PELOD

Indications are like ART

so Fluid is easy Easier to put a line in a child who is not “squishy” At 5% FO have the conversation and consider diuretics At 10-15% warm up the machinery Solute is hard Perhaps when One has insufficient room to delivery nutrition, medications The child has a rising K, BUN, Phos When the child is febrile (hypermetabolic) But it really comes down to “gut sense” and experience. Personally I find RRT safe and therefore one has a better control of solute and fluid but being on RRT….