1. Continuous renal replacement therapy
신장내과
R4 위지완

2. CRRT
Either dialysis (diffusion-based solute removal) or filtration (convection-based solute and water removal) treatments that operate in a continuous mode
Continuous renal replacement therapy (CRRT) was developed in the 1980s in an effort to
provide artificial kidney support to patients who could not tolerate traditional hemodialysis
Contraindications
Advance directives indicating that the patient does not want dialysis
The patient or his or her health care proxy declines continuous renal-
replacement therapy
Inability to establish vascular access
Lack of appropriate infrastructure and trained personnel for continuous
renal-replacement therapy

3. Indications
In critically ill patients with renal failure & hemodynamic instability

4. What is better in AKI patients ?
IHD vs CVVH → 62.5% vs 58.1% (p=0.43)
IHD vs CVVHDF → 31.5% vs 32.6% (p=0.98)
Meta-analysis of 15 randomized, controlled trials
CRRT vs IHD (RR 0.92 vs 1.12)
No significant survival benefit !!!
316명
2. 360명 trial

5. Principles of CRRT Use a semi-permeable membrane Waste Management
Diffusion, convection
Fluid Management
Ultrafiltration

6. Ultrafiltration
Plasma water is forced across a semipermeable membrane by hydrostatic pressure
Ultrafiltration↑
Pressures applied to the filter ↑
Rate blood passes through the filter ↑
Ultrafiltration uses positive pressure on the blood side of the membrane and negative pressure on the fluid side of the membrane to influence the movement of fluid. The gradient, positive to negative, results in fluid removal from the patient. The ultrafiltration rate depends on the pressure applied to the filter, inside and outside the fibers. Minimal waste removal happens by convection during ultrafiltration.

7. Diffusion
Movement of a solute across a membrane via a concentration gradient
Diffusion is used for removing small waste molecules (also known as solutes) during hemodialysis. In CRRT, blood flows through the hollow fibers of the dialyzer, and a cleansing fluid , known as a dialysate solution, flows in the opposite direction (See Image). This configuration maximizes the removal of wastes. Throughout this process, the waste molecules move from a higher concentration in the blood to a lower concentration in the dialysate

8. Convection
Movement of solutes through a membrane by the force of water
“Solvent drag”
Maximized by replacement fluids
Fluid flow rate↑ ∝ convection ↑
Convection, sometimes referred to as solvent drag, is used to remove both larger and smaller waste molecules. The difference in pressure between your blood and the replacement fluids (known as substitution solution), which creates a solvent drag for small and large waste molecules across the membrane. The solvent drag leads to the removal of waste from your blood. The faster the replacement fluid flows, the more waste is removed from your blood.

10. Slow Continuous Ultrafiltration (SCUF)
Dialysate (X), replacement fluid (X)
Ix : fluid overload without uremia or electrolyte imbalance
Remove water : ultrafiltration
Effluent bag = fluid removed from the patient

11. Continuous Veno-venous Hemofiltration (CVVH)
Dialysate (X), replacement fluid (O)
Ix : uremia or severe pH or electrolyte imbalance
Remove solute : convection (good at removal of large molecules)
Effluent bag = fluid removed from the patient + replacement fluid

12. Continuous Veno-venous Hemodialysis (CVVHD)
Dialysate (O), replacement fluid (X)
Similar to traditional hemodialysis
Effective for removal of small to medium sized molecules
Solute removal : diffusion
Effluent bag = fluid removed from the patient + dialysate
While CVVHD can be configured to allow a positive or zero fluid balance, it is more difficult than with CVVH because the rate of solute removal is dependent upon the rate of fluid removal from the patient.

13. Continuous Veno-venous Hemodiafiltration (CVVHDF)
Dialysate (O), replacement fluid (O)
Solute removal : diffusion & convection
Effluent bag = fluid removed from the patient + dialysate + replacement fluid
replacement fluid allows adequate solute removal even with zero or positive net fluid balance for the patient

14. Dialysate
Crystalloid solution containing various amounts of electrolytes, glucose, buffers
Dialysate flow rates : ml/h
Hemosol
Dialysate is any fluid used on the opposite side of the filter from the blood during blood purification.
As with traditional hemodialysis therapy, the dialysate is run on the opposite side of the filter, countercurrent to the flow of the patient’s
blood.
The countercurrent flow allows a greater diffusion gradient across the entire membrane, increasing the effectiveness of
solute removal.

15. Replacement fluid Convective solute removal↑
Replacement fluid rates : 1000 – 2000 ml/h
Post –filter : ≤ 1/3 of blood flow rate
(ex, 100ml/min → 6000ml/h , ≤ 2000ml/h)
Pre-dilution : solute clearance↑, clotting↓
Post-dilution : small solute clearance better
Rates slower than this are not effective for convective solute removal.
Replacement fluids administered pre-filter reduce filter clotting and can be administered at
faster rates (driving higher convection) than fluids administered post-filter. The downside of
pre-filter replacement fluids is that they invalidate post-filter lab draws; the lab results will
show the composition of the replacement fluid rather than that of the effluent.
pre-dilutional fluid replacement was reported to increase solute clearances in spontaneously driven circuits [2].
Subsequently, with advances in technology and the introduction of pumped veno-venous systems, pre-dilution – by diluting solutes
entering the hemofilter – was shown to reduce small solute clearances, compared to post-dilution

16. Blood flow rate Common before : 100 - 150 ml/min
Now : ml/min to reduce the risk of thrombosis

17. Effluent Fluid that drains out of the hemofilter
Plasma water + removed solutes + dialysate + replacement fluid
Recommend effluent volume : 20–25ml/kg/h in AKI
Generally necessary to prescribe : 25–30ml/kg/h
In conclusion, there are now consistent data from two large multicenter trials showing no benefits of increa-
sing CRRT doses in AKI patients above effluent flows of 20–25ml/kg/h. In clinical practice, in order to achieve a
delivered dose of 20–25ml/kg/h, it is generally necessary to prescribe in the range of 25–30ml/kg/h, and to minimize
interruptions in CRRT.

18. Vascular Access Venovenous vs arteriovenous
Rt. jugular v. > femoral v. > Lt. jugular v. > subclavian v.
> 1-3 weeks : tunneled catheters
“USG-guided”
USG-guided

19. Anticoagulation Heparin-induced thrombocytopenia All heparin stop
Unfractionated or LMWH
Heparin-induced thrombocytopenia
All heparin stop
Direct thrombin inhibitors
Factor Xa inhibitors
With increased bleeding risk : avoid heparinization

20. Anticoagulants

21. Anticoagulants Nafamostate mesilate (Futhan)
Synthetic proteinase inhibitor that acts on several serine proteases (thrombin, fXa, fXIIa)
tissue factor ± fVIIa complex inhibition
extracorporeal elimination (low molecular mass)
short half-life (20 min)
≫ limits systemic anticoagulation
No anticoagulation
Pre-dilution replacement fluid↑, blood flow rate↑

22. Prescription for CRRT < 본원 기본 setting >
CVVHDF
100 ml/min
1000ml/h
Hemosol, 1000ml/h
Heparin or Futhan
Form of therapy (CVVH, CVVHD, CVVHDF)
Blood flow rate
Type and rate of replacement fluid
Type and rate of dialysis
Type and dose of anticoagulation
Net fluid goal
monitor electrolyte
the fluid that drains out of the hemofilter; a combination of plasma water, removed
solutes, spent dialysate and replacement fluid volumetes and acid-base status every 6 to 8 hours

23. Summary of guidelines
Ix : life-threatening changes in fluid, electrolyte, acid-base balance
Vascular access : Rt. jugular > femoral > Lt. jugular > subclavian
Effluent flow rate 20-25ml/kg/hr in AKI (actually higher)
Anticoagulation : citrate > heparin

24. Complication Vascular access
infection, vascular injury, arterial puncture, hematoma, hemothorax, pneumothorax, arteriovenous fistula, aneurysm, thrombus formation
During therapy
hypotension, arrhythmias, fluid & electrolyte disturbances, nutrient losses, hypothermia, bleeding, hypokalemia, hypophosphatemia, potential underdosing of drugs