Continuous renal replacement therapy 신장내과 R4 위지완

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

Indications In critically ill patients with renal failure & hemodynamic instability

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

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

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.

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

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.

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

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

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.

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

Dialysate Crystalloid solution containing various amounts of electrolytes, glucose, buffers Dialysate flow rates : 600 - 1800 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.

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

Blood flow rate Common before : 100 - 150 ml/min Now : 200 - 250 ml/min to reduce the risk of thrombosis

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.

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

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

Anticoagulants

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↑

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

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

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