WHEN TO CONSIDER RRTTimothy E BunchmanFounder PCRRTwww.pcrrt.comtbunchman@mcvh-vcu.edu

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

• Faragson3 found PRISM to be a poor outcome predictor in patients treated with HD

• Zobel4 demonstrated that children who received CRRT with worse illness severity by PRISM score had increased mortality

1. Bone Marrow Transplant 13:613-7, 199423. Pediatr Nephrol 7:703-7, 19944. 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)

Mean+SEMean-SE

Mean

OUTCOME

%FO

at C

VVH

Initia

tion

0

5

10

15

20

25

30

35

40

45

Death Survival

p = 0.03

Goldstein SL et al: Pediatrics 2001 Jun;107(6):1309-12

Fluid Overload as a Risk Factor

Foland et al, CCM 2004; 32:1771-1776

N=113*p=0.02; **p=0.01

Gillespie et al, Pediatr Nephrol (2004) 19:1394-1999

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 8.5 + 6.8 years (2 days to 25.1 years)Mean weight 33.7 + 25.1 kg (1.9 to 160 kg)Median 3 ICU days prior to CRRT initiation4Range 0 to 103 days467%less than 7 days

Goldstein SL et al: Kidney International 2005

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

Variable (values mean +/- SD) Survivors Non-Survivors

p-value (t-test)

Age (years) 8.5 + 6.7 8.5 + 7.2 NS

Weight (kg) 34.2 + 25.4 31.7 + 25.8 NS

PRISM at ICU Admit 14.3 + 8.2 16.2 + 9.7 NS

PRISM at CRRT Initiation 13.9 + 8.2 18.6 + 7.2 < 0.003

CVP at CRRT Initiation 16.5 + 6.1 21.2 + 6.6 < 0.003

BUN at CRRT Initiation 61.1 + 41.8 67.8 + 45.7 NS

% FO at CRRT Initiation 14.2 + 15.9 25.4 + 32.9 < 0.03

No. of Pressors 1.4 + 1.1 1.7 + 1.1 NS

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 OutcomeRonco et al. Lancet 2000; 351: 26-30

Conclusions: Minimum UF rates should be ~ 35 ml/kg/hr Survivors had lower BUNs than non-survivors

prior to commencement of hemofiltration

425 patientsEndpoint = survival 15 days

after D/C HF

146 UF rate 20ml/kg/hrsurvival significantly lower

in this group compared to the others

139 UF rate 35ml/kg/hrp=0.0007

140 UF rate 45ml/kg/hrp=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; 180-184 • Walters et al Pediatr Neph 2009 24; 37-38

Stem Cell Transplant: ppCRRT• 51 patients in ppCRRT with SCT• Mean %FO = 12.41 + 3.7%. • 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. 2008 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 12 + 4.8 years• Mean weight 44 + 21 kg

• PELOD• Mean = 27 + 10• Median = 22 (range 11-42)

ppCRRT [Cytokine] % Change: Convection vs. Diffusion

Cytokine Convection Diffusion pTNF-alpha -3.7 + 9.6 3.9 + 9.1 0.08

IL-1 beta -2.8 + 14.8 1.4 + 12.9 0.46

IL-6 32.7 + 102.8 -2.6 + 18.4 0.21

IL-8 -29.1 + 26.0 - 8.3 + 17.2 0.018

IL-10 -44.6 + 29.0 3.1 + 45.0 0.007

IL-18 -13.6 + 17.9 16.9 + 24.7 0.002PELOD -22 + 34 -6 + 30 0.26

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….