1. Definition
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

2. Indications In general: Intensive Care Severe acid-base disorders
Severe electrolyte abnormalities
Refractory volume overload
Uremia
Intoxications
Intensive Care
Severe septic shock

3. 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

4. CRRT Circuit Vascular access Blood flows Machinery Dialyzer
Circuit volume
Dialysate/ replacement fluid rates
Anticoagulation

5. 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

6. Vascular Access Principles Problems
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

7. Recirculation Access recirculation may limit clearances
Subclavian 4.1%
Femoral 13.5 cm %
Femoral 19.5 cm %
flow 300 ml/min)
More problematic in IHD than CRRT .

8. Mechanisms of Solute Removal
Diffusion
Ultrafiltration
Diffusion + Ultrafiltration
Adsorbtion

10. Ultrafiltration
Pressure
Membrane
Membrane Uf Uf
The transfer of solute in a stream of solvent, across a semi-permeable membrane, mediated by a hydrostatic force
Coffee maker analogy of Ultrafiltration
Removal of large volumes of solute and fluid via convection

11. Dialysate/Ultrafiltrate
Solute clearance
Blood
Membrane
Dialysate/Ultrafiltrate

12. Convective solute clearance
Blood
Membrane
Ultrafiltrate

13. Convective solute clearance
Blood
Membrane
Ultrafiltrate

14. Blood In to waste Blood Out (from patient) HIGH PRESS LOW PRESS
(to patient)
HIGH PRESS
LOW PRESS
Convection: The movement of solutes with a water-flow, “solvent drag”, the movement of membrane-permeable solutes with ultra filtered water

15. SCUF Slow Continuous Ultrafiltration
Access
Return
Effluent
Fluid removal
Minimal solute clearance
CVVHDF, or Continous Veno-venous hemofiltration, provides solute removal by diffusion and convection simultanously, and patient fluid removal if desired.
It offers hight volume ultrafiltration using replacement fluid which can be given pre-filter (pre-dilution) or post filtre (post-dilution). Simultaneously dialysate is pumped at counter flow to blood

16. Convective solute clearance
Replacement fluid
SCUF
CVVH
Removal of large volumes of solute and fluid via convection
Replacement of excess UF with sterile replacement fluid

17. CVVH Continuous Veno-Venous Hemofiltration
Access
Return
Effluent
Replacement
Fluid removal
Fluid replacement
Solute clearance
Convection
Minor amount diffusion
CVVHDF, or Continous Veno-venous hemofiltration, provides solute removal by diffusion and convection simultanously, and patient fluid removal if desired.
It offers hight volume ultrafiltration using replacement fluid which can be given pre-filter (pre-dilution) or post filtre (post-dilution). Simultaneously dialysate is pumped at counter flow to blood

18. Extracorporeal Clearance
Hemofiltration clearance (ClHF = Qf x S)
Qf = Ultrafiltration rate
S = Seiving coefficient
Hemodialysis clearance (ClHD = Qd x Sd)
Qd = Dialysate flow rate
Sd = Dialysate saturation
Hemodialfiltration clearance
ClHDF = (Qf x S) + (Qd x Sd) 16

19. Sieving Coefficient (S)
Capacity of a solute to pass through the hemofilter membrane
S = Cuf / Cp
Cuf = solute concentration in the ultrafiltrate
Cp = solute concentration in the plasma
S = 1 Solute freely passes through the filter
S = 0 Solute does not pass through the filter 12

20. Sieving coefficient
Ratio of solute concentration in ultrafiltrate to solute concentration in blood
Element
Sieving Coefficient
Sodium
0.993
Valine
1.069
Potassium
Cystine
1.047
Chloride
Methionine
1.0
Bicarbonate
Isoleucine
1.010
Calcium
Leucine
1.014
Phosphate
1.04
Tyrosine
1.089
Albumin
Phenylalanine
1.078
Urea
Lysine
1.080
Creatinine
Histidine
1.109
Glucose
Threonine
1.256
Urate
1.02
Total protein
0.02
magnesium
0.9
Total bilirubin
0.03

21. 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 13

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

23. Principles of Hemodialysis
Solute clearance by diffusion
Suitable for removal of small molecules, and most middle molecules

24. The use of diffusion (dialysis fluid) to achieve clearance

25. Diffusive solute clearance
Blood
Membrane
Dialysate

26. Diffusive solute clearance
Blood
Membrane
Dialysate

27. Counter current flow
Blood
Membrane
Dialysate

28. Dialysate Out Dialysate In Blood In Blood Out to waste (from patient)
(to patient)
HIGH CONCENTRATION
LOW CONCENTRATION

29. CVVHD Continuous Veno-Venous Hemodialysis Dialysate Access
Return
Effluent
Dialysate
Fluid removal
Solute removal
(small molecules)
Counter-current dialysis flow
Diffusion
Back filtration

30. Dialysate Saturation (Sd)
Sd = Cd / Cp
Cd = solute concentration in the dialysate
Cp = solute concentration in the plasma
Decreasing dialysate saturation
Increasing molecular weight
Decreases speed of diffusion
Increasing dialysate flow rate
Decreases time available for diffusion 15

31. Dialysate Saturation (Sd)
Countercurrent dialysate flow ( ml/min) is always less than blood flow ( 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 14

32. Replacement Fluid/Dialysate
Must contain:
Sodium
Calcium (except with citrate)
Base (bicarbonate, lactate or citrate)
May contain:
Potassium
Phosphate
Magnesium

33. CRRT Set up
The Machine….

34. CVVHDF Continuous Veno-Venous Hemodiafiltration
Dialysate
Access
Return
Fluid removal
Solute removal
(small and larger solutes)
Diffusion plus Convection
Replacement S
Effluent

35. Blood Flow/Blood Pump Speed
Range from 10 to 450 ml/min
Average ml/min
Higher blood flow could decrease filter
clotting
Factors affecting QB :
- Catheter lumen size
- Blood viscosity
A good access is crucial ,most of the trouble shooting refer to vascular access

36. Effect of filtration on CVVH
Hematocrit
30%
Hematocrit
60%
A filtration fraction of more than % greatly increases
blood viscosity within the circuit, risking clot and malfunction.

37. Blood flow requirements for CRRT to maintain filtration fraction at 25%
The degree of blood dehydration can be
estimated by determining the filtration fraction
(FF), which is the fraction of plasma water
removed by ultrafiltration:
FF(%) = (UFR x 100) / QP
where QP is the filter plasma flow rate in ml/min.
Ultrafiltration rate (mls/hr)
Minimum Qb/min
1500
100
2000
130
2500
155
3000
200
4000
265

38. 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

39. Impact of filter clotting
Decrease in dialysis dose
Wasted nursing time
Increase in cost

40. Renal Replacement Therapy Dose
Dose = amount of solute clearance
Modifications required based on:
Patient weight
Interruptions
Recirculation

41. 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 < %
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’ ml/min
Haemofiltration with dialysis: ‘GFR’ ml/min 29

42. 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

44. 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 27

45. > Blood flow = > Elimination
< MW = > Elimination
> Dialysate flow = > Elimination
Free available drug

46. < VD = > Elimination
> Water solubility = > Elimination

50. TOXOKINETICS MORE THAN OUTCOMES

51. 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

52. Ongoing dilemas in CRRT
World practice
HVUF