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?)