Renal Replacement Therapy For Pediatrics

Theory and Practice Eileen Tsai, MD

June 11, 2014

General Principals

Kids are NOT small adults!!! Unfortunately current day equipment is not

designed for children! Most of the CRRT theory and practice is similar

between adults and children

Overview

Peds vs Adults: Indications (Same) Transport mechanisms (Same) Available Modalities (Same) Dosing? (Same) Equipment (Same- unfortunately!)

Anti-coagulation Citrate (preferred in pediatrics) Heparin

CRRT Indications Acidosis (metabolic) Electrolytes- (severe refractory)

K, Ca, ?Phos Ingestions, Inborn error of metabolism Overload of Fluids

Increasing evidence that earlier is better 75% of our calls Is there a role for calculation of a fluid overload

index? Uremia

Encephalopathy, bleeding, pericarditis

Therapeutic Goals

Clearance- AEIU- describes the movement of solutes via diffusion, convection or a combination of the two

Ultrafiltration (UF)- O- describes the net removal of fluid (convection=fluid carrying solute)

Usually renal replacement therapy involves both processes

Therapeutic Goals

Remember that is most cases:

CRRT is supportive therapy Allows for:

Improved vent management Optimal nutrition +/- improved hemodynamics

Molecular Transport Mechanisms of Renal Replacement Therapy

Diffusion Convection/Ultrafiltration (Adsorption)

Diffusion vs. Convection C

lear

ance

Diffusive Clearance

Convective Clearance

Molecular Weight 100 1,000 10,000 10

CRRT Terminology

CVVH- Hemofiltration use of a hydrostatic pressure gradient to induce the filtration

(or convection) of plasma water across the membrane of the hemofilter

CVVHD- Hemodialysis transport process by which a solute passively diffuses down

its concentration gradient from one fluid compartment (either blood or dialysate) into the other

CVVHDF- Hemodiafiltration dialysis + filtration. Solute loss occurs by diffusion and convection

CRRT : Slow Continuous

Ultrafiltration (SCUF) Return

Effluent

Access

QUF (100-300 mL/hr)

Vol control, minimal solute clearance!! Ultrafiltration vol = Pt’s Wt loss

QB (50-100 mL/min)

CVVH : Continuous Hemofiltration

QUF (500-2000 mL/hr)

Return

Effluent

Access

Replacement QR

Predilution

Postdilution

Convective solute removal Clearance for all solutes =UF

QB (50-200 mL/min)

Return

Access CVVHD : Continuous Hemodialysis

Dialysate QDi

QDo

Diffusive solute removal Limited to small solute

QUF = Q Di – Q Do (100-300 mL/hr)

QB (50-200 mL/min)

Return

Access CVVHDF : Continuous Hemodiafiltration

Dialysate QDi

QDo

Replacement QR

Postdilution Convective + Diffusive solute removal Small to large molecules

Predilution

Effluent

Importance of Pediatric Access

Practical Considerations for CRRT QB: The access Issue

Equipment- Smaller vessels means small access smallest access is about an 7 to 8 french- extremely

difficult to place in anyone <3Kg Smaller access means:

Lower blood flows resistance to flow is ~ to the radius4- so blood flow is

generally limited by the size of access not necessarily what the patient “can provide”

Increased clotting!!!! Good news- CRRT is generally not QB limited

Practical Considerations for CRRT QB: The access Issue

Typical blood flow= BSAx100ml/min E.g. adult patient 1.73x100=170ml/min Baby 0.3m2= 30ml/min Lowest rate 10ml/min and the pump goes by 10s

Take home point- access is king and without you cannot successfully dialyze a patient

Practical Considerations for CRRT QB issues: <50 ml/min

Clinical Scenario I set the QB 30ml/min, machine is working. Uh-oh, access pressure is 0. What is an access disconnect alarm? The machine shut down.

How do I troubleshoot? 30 ml/min may not generate enough negative pressure

Target negative pressure -20 to -30

C-clamp goes between access and access pressure pod Too tight and access pressure skyrockets. This is bad… May be necessary on both access and return if CRRT is used

concurrently with ECMO

Practical Considerations for CRRT Prescription: Qd+Qr

What clearance do you prescribe? We generally aim for 2000-3000 ml/hr/1.73m2

Based on adult CVVH data How do we estimate clearance?

Predilution + dialysate rate (PrismaFlex) Dialysate rate (Next-stage)

E.g. Child with BSA of 1m2

Predilution of 400ml/hr Dialysate of 800ml/hr Clearance =1200ml/hr

UF of ~1-2cc/kg/hr (NET)

Practical Considerations for CRRT Solutions

Dialysate: Prismasate 4K/0Ca vs. 2K/0Ca Bicarbonate based- essentially lactate free

Predilution: Pharmacy made Varying degrees of buffer There are now commercially available pre-dilution

solutions approved for infusion Primasol Custom solution

Practical: Equipment We have to rely on equipment that is designed for adults- So

whats the big deal? Access and blood flows- this turns out not be such a big deal

except when Qb is limited to >50ml/min. Big problem is the total circuit volume Total circuit volume ~100cc Blood volume is ~80cc/kg

Adult- 80x60kg= ~5L Baby 80x3kg= 240ml Now lets put them on a circuit with a fill of 100cc! Add in hypotension and anemia Add in bradykinin release syndrome (some filter sets-AN69)

Initiation of CRRT

Optimization of Patient Hemodynamics:

Volume- want several 10cc/kg NS boluses available Pressors- start early Blood- in some circumstances needs to be hanging

Acid base status Bradykinin release syndrome AN69 membrane

(Prismaflex) More tolerated membrane polyarylethersulfone (PAES)

HF20, HF1000, HF1400 (Prismaflex) Not applicable to HF400 and HF700 (Next-stage)

Initiation of CRRT

Optimization of Machine Initial blood flows are as low as possible Often we will go up 10cc/min every 20 minutes

after patient is on Prime is occasionally with pRBCs, 5% albumin or

saline In extreme cases (smaller than 10kg) we may have

blood running into the patient or prime machine with blood

Ongoing Therapy

In smaller patients- errors are magnified Especially true with volume removal calculations

An adult may be able to tolerate a +/- 500ml fluid status In a small child this amount could mean room air and

intubation (or worse!)

Citrate Anti-coagulation: Mechanism

Ca is an essential cofactor for many of the cascade proteins

By removing the ionized Ca from blood; coagulation is prevented; i.e. banked blood

Desire a Post-filter iCa of around 0.4mmol/L which requires a citrate concentration of ~ 6mmol/L

The machine is anti-coagulated NOT the pt

Sites of Action of Citrate CONTACT PHASE

XII activation XI IX

TISSUE FACTOR TF:VIIa

THROMBIN

fibrinogen

prothrombin

Xa Va VIIIa Ca++ platelets

CLOT

monocytes / platelets / macrophages X

Phospholipid surface

CITRATE

Citrate in Practice

Citrate in Practice

Standardized Citrate ACD(A) Solution Citrate rate in ml/hr will be 1.5 x the BFR the

PRISMA machine at ml/min. (eg If BFR is 100ml/min, citrate is 150mls/hr)

Ca infusion (ie. 8gms Calcium Chloride in 1L NS, Calcium Gluconate is 16gms in 1L). This will run at 40% of the citrate flow rate. (eg citrate rate = 150 mls/hr then CaCl rate = 60 mls/hr)

Citrate Monitoring

2 hour after initiation of therapy and every 6 hours thereafter, send Post-filter ionized Ca (drawn from the return line,

blue sample port) Systemic ionized Ca (drawn from patient) along with

a total Ca

Citrate Complications

Citrate-induced hypocalcemia (Citrate Lock) If citrate is not effectively cleared (via dialysis or

hepatic metabolism) pts ionized Ca will drop while total rises; i.e. no longer regional

Hold ACD-A solution for several hours followed by adjustment of citrate infusion rate (70%)

Pts with hepatic dysfunction are at greatest risk

Citrate Complications

Citrate induced metabolic Alkalosis Citrate is metabolized to bicarb Original paper described several pts needing dilute

HCl infusion to correct resultant alkalosis Adjustment of predilution/dialysate, some centers

use a 22 meq/L Bicarb solution Adjustment of TPN acetate/Cl ratio

Take away point #1

You will always need to take into account the Citrate and Ca infusion rates when you make your UF calculations Total Fluid Removal Rate _____ml/hr=

Net UFR _____ml/hr + citrate rate _____ml/hr + CaCl rate ____ml/hr

So… for no UF at a BFR of 100 you need to remove 210ml/hr (3.5ml/min)

Take away point #2

Citrate is for the machine- so adjustments in the citrate rate are made to optimize iCa measurements from the blue port (think about where citrate enters)

Ca is for the patient- so adjustments in the Ca rate are made to optimize iCa measurements from the patient (think about where Ca enters)