Continuous Renal Replacement Therapy (CRRT)

“ Any extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours /day.”

Bellomo R., Ronco C., Mehta R, Nomenclature for Continuous Renal Replacement Therapies, AJKD, Vol 28, No. 5, Suppl 3, November 1996

Definition

IndicationsIn general:

Severe acid-base disorders Severe electrolyte abnormalities Refractory volume overload Uremia Intoxications

Intensive Care Severe septic shock

Why CRRT?

Reduces hemodynamic instability preventing secondary ischemia

Precise Volume control/immediately adaptable Uremic toxin removal Effective control of uremia, hypophosphatemia, hyperkalemia

Acid base balance

Rapid control of metabolic acidosis

Electrolyte management

Control of electrolyte imbalances

Management of sepsis/plasma cytokine filter

CRRT Circuit

Vascular accessBlood flows MachineryDialyzer Circuit volumeDialysate/ replacement fluid ratesAnticoagulation

Vascular Access

Double lumen catheter Catheter able to provide sufficient blood flow 11 French and greater Avoid kinking Secure connections, make them visible Right size at the right place

Vascular AccessPrinciples

Vessel(s) and catheters should be large enough to permit blood flow rates > 300 mls/min

Problems Poor flow (high positive/negative pressures) Bleeding Clotting Infection Venous stenosis

RecirculationAccess recirculation may limit clearances

Subclavian 4.1% Femoral 13.5 cm - 22.8% Femoral 19.5 cm - 12.6% (@Blood flow 300 ml/min)

More problematic in IHD than CRRT.

Mechanisms of Solute Removal

Diffusion

Ultrafiltration

Diffusion + Ultrafiltration

Adsorbtion

UltrafiltrationPressure

Membrane

UfUf

The transfer of solute in a stream of solvent, across a semi-

permeable membrane, mediated by a hydrostatic force

Membrane

Coffee maker analogy of UltrafiltrationRemoval of large volumes of solute and fluid via convection

Solute clearanceMembraneBlood Dialysate/Ultrafiltrate

Convective solute clearance

MembraneBlood Ultrafiltrate

Convective solute clearance

MembraneBlood Ultrafiltrate

Convection: The movement of solutes with a water-flow, “solvent drag”, the movement of membrane-permeable solutes with ultra

filtered water

Blood In

Blood Out

to waste(from patient)

(to patient)

HIGH PRESS

LOW PRESS

SCUFSlow Continuous

UltrafiltrationAccess

Return

Effluent

Fluid removal Minimal solute

clearance

SCUF CVVH

Replacement fluid

Removal of large volumes of solute and fluid via convectionReplacement of excess UF with sterile replacement fluid

Convective solute clearance

CVVHContinuous Veno-Venous

HemofiltrationAccess

Return

Effluent

Replacement

Fluid removal Fluid replacement Solute clearance Convection Minor amount

diffusion

Extracorporeal Clearance

Hemofiltration clearance (ClHF = Qf x S)Qf = Ultrafiltration rateS = Seiving coefficient

Hemodialysis clearance (ClHD = Qd x Sd)Qd = Dialysate flow rateSd = Dialysate saturation

Hemodialfiltration clearance

ClHDF = (Qf x S) + (Qd x Sd)

Sieving Coefficient (S)

Capacity of a solute to pass through the hemofilter membrane

S = Cuf / Cp

Cuf = solute concentration in the ultrafiltrateCp = solute concentration in the plasmaS = 1 Solute freely passes through the filterS = 0 Solute does not pass through the filter

Element Sieving Coefficient Element Sieving Coefficient

Sodium 0.993 Valine 1.069

Potassium 0.975-0.99 Cystine 1.047

Chloride 1.05-1.088 Methionine 1.0

Bicarbonate 1.12-1.137 Isoleucine 1.010

Calcium 0.64-0.677 Leucine 1.014

Phosphate 1.04 Tyrosine 1.089

Albumin 0.0002-0.01 Phenylalanine 1.078

Urea 1.019-1.05 Lysine 1.080

Creatinine 1.02-1.037 Histidine 1.109

Glucose 1.04 Threonine 1.256

Urate 1.02 Total protein 0.02

magnesium 0.9 Total bilirubin 0.03

Sieving coefficientRatio of solute concentration in ultrafiltrate to solute concentration in blood

Determinants of Sieving Coefficient

Protein binding Only unbound drug passes through the

filter Protein binding changes in critical illness

Drug membrane interactions Adsorption of proteins and blood products

onto filter Related to filter age Decreased efficiency of filter

Relationship Between Free Fraction (fu) and Sieving Coefficient (S)

Principles of Hemodialysis

Solute clearance by diffusion

Suitable for removal of small molecules, and most middle molecules

DialysisThe use of diffusion (dialysis fluid) to achieve clearance

Diffusive solute clearance

MembraneBlood Dialysate

Diffusive solute clearance

MembraneBlood Dialysate

Counter current flowMembraneBlood Dialysate

Dialysate Out

Dialysate In

Blood In

Blood Out

to waste

(from patient)

(to patient)

HIGH CONCENTRATIONLOW CONCENTRATION

CVVHD Continuous Veno-Venous Hemodialysis

S

Access

Return

Effluent

Fluid removal

Solute removal

(small molecules)

Counter-current dialysis

flow

Diffusion

Back filtration

Dialysate

Dialysate Saturation (Sd)

Sd = Cd / CpCd = solute concentration in the dialysateCp = solute concentration in the plasma

Decreasing dialysate saturation Increasing molecular weight

Decreases speed of diffusion Increasing dialysate flow rate

Decreases time available for diffusion

Dialysate Saturation (Sd)

Countercurrent dialysate flow (10 - 30 ml/min) is always less than blood flow (100 - 200 ml/min)

Allows complete equilibrium between blood serum and dialysate

Dialysate leaving filter will be 100% saturated with easily diffusible solutes

Diffusive clearance will equal dialysate flow

Replacement Fluid/DialysateMust contain:SodiumCalcium (except with citrate)Base (bicarbonate, lactate or citrate)

May contain:PotassiumPhosphateMagnesium

CRRT Set upThe Machine….

CVVHDFContinuous Veno-Venous Hemodiafiltration

Replacement

S

Access

Return

Effluent

Dialysate

Fluid removal Solute removal (small and larger solutes)

Diffusion plus Convection

Blood Flow/Blood Pump Speed

·Range from 10 to 450 ml/min·Average 125-150 ml/min·Higher blood flow could decrease filter clotting·Factors affecting QB :

- Catheter lumen size - Blood viscosity

Effect of filtration on CVVH

Hematocrit30%

Hematocrit60%

A filtration fraction of more than 25 - 30% greatly increasesblood viscosity within the circuit, risking clot and malfunction.

Blood flow requirements for CRRT to maintain filtration fraction at 25%

Ultrafiltration rate (mls/hr) Minimum Qb/min

1500 100

2000 130

2500 155

3000 200

4000 265

The degree of blood dehydration can beestimated by determining the filtration fraction

(FF), which is the fraction of plasma waterremoved by ultrafiltration:FF(%) = (UFR x 100) / QP

where QP is the filter plasma flow rate in ml/min.

Anticoagulation options•None (- if marked coagulopathy)•Unfractionated heparin•LMW Heparin•Citrate•Direct Thrombin Inhibitors

• r-Hirudin • Argatroban

•Prostacycline

•Assessment: Need ongoing anticoagulation Risk of bleeding with heparin

2% per day 3.5-10% of deaths 25% of new hemorrhagic episodes

Impact of filter clotting

Decrease in dialysis doseWasted nursing timeIncrease in cost

Renal Replacement Therapy Dose

Dose = amount of solute clearanceModifications required based on:

Patient weight Interruptions Recirculation

Dosage Adjustments in CRRT

Loading doses Loading dose depends solely on volume of distribution

Maintenance doses Standard reference tables Base on measured loses

Will the drug be removed? Pharmacokinetic parameters

Protein binding < 70 - 80% Normal values may not apply to critically ill patients

Volume of distribution < 1 L/kg Renal clearance > 35%

How often do I dose the drug? Haemofiltration: ‘GFR’ 10 - 20 ml/min Haemofiltration with dialysis: ‘GFR’ 20 - 50

ml/min

Dosage Adjustments in CRRT

Frequent blood level determinations Aminoglycosides, vancomycin

Reference tables Bennett's tables or the PDR recommendations

require an approximation of patient's GFR

Using Bennett's or the PDR’s tables, in most CVVH patients, drug dosing can be adjusted for a ‘GFR’ in the range of 10 to 50 ml/min

Drug Removal During CRRT

Limited to case reports or series of patients

Different filter brands, sizes, flow rates

Limited information in many reports

Artificial models and predictions have no clinical value

< MW = > Elimination

> Blood flow = > Elimination

> Dialysate flow = > Elimination

Free available drug

< VD = > Elimination

> Water solubility = > Elimination

TOXOKINETICS MORE THAN OUTCOMES

Ongoing dilemas in CRRT

Mode Clinically still part of the debate (sepsis vs. ARF)

Dose Ronco Trial Renal Study ATN Trial High Volume Ultrafiltration

IHD vs CRRT No diference in outcome in a RCT

Anticoagulation

World practice

HVUF

Ongoing dilemas in CRRT