血液透析原理及臨床適應症 台大醫院 外科部護理師 蔡壁如

Evolution of Renal Replacement Therapy Kramer, 1977 First CRRT (CAVH) 1994 Automated CRRT CRRT or SLEDD? Abel, 1913 First dialysis of animal Kolff, 1945 First dialysis in human Teschan, 1950s Daily dialysis in Korean war Since 1960s Chronic, intermittent hemodialysis (IHD) ( 24hrs q.w. 10-16hrs b.i.w. - 4-6hrs t.i.w. ) Daily dialysis? Contrib Nephrol. 2004; 145: 1-9

Basic Principle of Renal Replacement Therapy Diffusion Solute from higher concentration to lower concentration Ultra-filtration Fluid trough semi-permeable membrane driven by pressure gradient Convection Solute and fluid (Depending on molecular weight and size) by ultra-filtration Adsorption Molecular adhesion to inner surface of semi-membrane NEJM 336:1303-1309

Diffusion

Ultra-filtration

Convection

Adsorption

Molecular weights

Molecules sizes

Molecules Size

Low-Flux Membrane

High Flux Membrane

IL-6, TNF-α 20000 Molecular weights cut-offs <30000> IL-1, IL-8 IL-1, IL-8, TNF-a

Clearance = QF x SC QF= filtration amount SC=sieving coefficients

Hemodialysis NEJM 336:1303-1309

Hemofiltration NEJM 336:1303-1309

Component of renal replacement therapy Membrane Vascular access Anti-coagulant Dialysate Renal replacement fluid

Choice of membrane Substituted cellulose dialyzers : hydroxyl group Cellulose acetate, diacetate, triacetate Synthetic dialyzers : Polysulfone (PS) Polyamide (PA) Polyacrylonitrile (PAN) Polymethylmethacrylate (PMMA) American Journal of Kidney Disease, Vol 35, NO 5(May), 2000:pp980-991

Choice of membrane Biocompatible membrane (activate less complement and greater higher 2-microglobulin clearance, greater hydraulic permeability.low and high-flux synthetic membranes) Hypotension and prolongation of ARF in biocompatible membranes Adsorptive vs. nonadsorptive membrane in CRRT American Journal of Kidney Disease, Vol 35, NO 5(May), 2000:pp980-991

Vascular access Grade C : avoided subclavian in adults Grade D : avoided femoral vein in neonates and young (femoral vein thrombosis is a significant problem) Grade C : Internal jugular vein Level II and III studies : Ultrasound guidance Re-circulation is likely to be significant for blood flow in excess of 200 c.c/min, but depending on catheter design and location The first international consensus conference on CRRT, 2002

Double lumen : Re-circulation rate under 250cc/min blood flow Subclavian , internal jugular vein < 3% Catheter length Femoral vein 24cm : 10%, 15cm : 18% Blood flow 400 cc/min : 38% in the femoral vein American Journal of Kidney disease , 1996

Anticoagulation Standard protocol Initial bolus 10-30 unit/kg of heparin Infusion 10-30 unit/kg to target ACT :170-220 seconds or PTT: 2 X N.J.Maxvold, T.E. Bunchman/Crit Care Clin 2003 19(2),563-575

Ideal replacement fluid/dialysate Principle: remove waste, supply lost Nearly plasma water Supply inadequate component Individualized Different disease

Dialysate (透析液) Na K Ca Mg GB +No8 140 2.0 3.5 1.0 GB +No9 137 2.5 Cl Acetate HCO3- GB +No8 107 5 - GB +No9 106 39 Units: mEq/L

Replacement Fluid (補充液) Na Ca Mg Cl HCO3- mEq/L CVVH A 液 147 5.2 2.8 155 - CVVH B 液 137 71 33 A+B 142 2.6 1.4 113 CVVH B 液 = H/S 2760ml + Rolikan 250ml

Hybrid therapies in ICU CRRT (Continuous Renal Replacement Therapy ) EDD ( Extended daily dialysis ) SLEDD ( Slow Low-efficient Daily Dialysis ) SLEDD-f (Sustained Low-efficiency Daily Diafiltration ) IHD ( Intermittent Hemo-dialysis )

CRRT iHD

Hybrid or Prolonged Intermittent Renal Replacement Therapies CRRT iHD

EDD: Extended Daily Dialysis Fresenius 2008H delivery system Double lumen Toray 2.0 m2 dialyzer Duration : 6 ~ 8 hrs Blood flow : 200 ml/min Dialysate flow rate : 300 (500) ml/min Dialysate potassium concentration 4 meq/L Dialysate bicarbonate concentration : 30 ~ 35meq/L American Journal of Kidney Disease, Vol 36, No 2 (August), 2000: pp 294-300

SLEDD ( Slow Low-efficiency Daily Dialysis ) Fresenius 2008H delivery system Double lumen Duration : 6 ~ 12 hrs Blood flow : 200 ml/min Dialysate flow rate : 300 ml/min Dialysate bicarbonate concentration : 30 ~ 35meq/L American Journal of Kidney Disease, 2000

SLEDD-f Sustained Low-efficiency Daily Diafiltration Fresenius 4008S Double lumen Duration : 8 ~ 12 hrs Blood flow : 200 ml/min Dialysate flow rate : 200-300 ml/min High Flux Dialyzer Online replacement fluid Nephrol Dial Transplant 2004 19:877-887

Nomenclature

HD treatment in ICU depend Treatment behavior Availability of treatment methods Organization of the unit Knowledge and experience of nurses Existence of nephrological unit in the hospital Cost Individual doctor must therefore know the advantages and disadvantage of different treatment options Kidney Blood Press Res2003;26:123-127

Daily hemodialysis and the outcome of acute renal failure ARF require CRRT is related high mortality and uremic damage to other organ systems Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity. Survival was the primary endpoint of the study Mortality rate : 28% Vs. 46% (daily H/D Vs. Alternate H/D ) N Engl J Med 2002;346:305-10

IHD vs CVVH IHD CVVH Diffusion Low-flux membrane High dialysate flow A few hours per day Technically demanding Less labor intensive Convection High-flux membrane Low dialysate flow Theory continuously Technically less demanding Labor intensive Journal of the American Society of Nephrology, 2001

IHD vs CVVH IHD CVVH Advantages Short duration Cheap Less labor-intensive Hemodynamic stability Better removal of cytokines Disadvantages Rapid hemodynamic change Technically sophisticated Continuous anticoagulation Patient immobility Intensive nursing requirement Increased expense

What is SLEDD-f ?? Sustained Low-Efficient Daily Diafiltration A conceptual and technical hybrid of continuous veno-veno hemofiltration(CVVH : convection) and intermittent hemodialysis (IHD : diffusion )

Advantage of SLEDD-f Patient mobility ↑ Anticoagulation ↓ hemodynamic stability – or ↑ Nursing labor ↓ Professional ↑ Cost ↓ American Journal of Kidney Disease, 2000

The predominant potential advantages of continuous renal replacement therapy Hemodynamics stability correction of hypervolemia and metabolic acidosis Better solute removal Recovery of renal function Biocompatibility Correction of malnutrition Better removal of cytokines Overall outcomes ? Kidney Blood Press Res2003;26:123-127 Journal of the American Society of Nephrology, 2001

Potential disadvantages of CRRT Need for continuous anticoagulation More difficult drug dosing Low efficiency interims of unit/ time ( e.g. Severe hyperkalemia) Nonselective solute removal : depletion syndrome with prolonged use of high Qf ? The Netherlands Journal of Medicine August 2003

Sustained low-efficiency dialysis in the ICU: Cost, anticoagulation, and solute removal Treatment parameters for current and previous SLED studies Author (reference) Kumar et al4 Marshall et al5 This study Treatment name EDD SLED SLEDD-f Hours/day 7.5 12 8 Days/week 6-7 4-7 6 Blood flow (ml/min) 200 100 300 Dialysate flow (ml/min) 350 Replacement fluid (ml/min) － 17 KI (2006) 70, 963-968

Sustained low-efficiency dialysis in the ICU: Cost, anticoagulation, and solute removal Measures of small solute removal CRRT SLED P-valve Morning serum creatinine after day 3 (μmoL/l) 136±49 120± 55 0.06 Time-average serum creatinine (μmoL/l) 95±49 0.03 Weekly Kt/V 7.1±2.1 8.4±1.8 <0.001 EKR ( ml/min) 31±10 31±7 NS EKR (ml/min) 28±9 29±6 KI (2006) 70, 963-968

Daily and weekly cost of SLED and CRRT Sustained low-efficiency dialysis in the ICU: Cost, anticoagulation, and solute removal Daily and weekly cost of SLED and CRRT SLED($) CRRT citrate ($) CRRT heparin ($) Supply cost/day 69.75 402.8 334.95 HD RN cost/day 168.75a 37.5 Total cost /day 238.5 440.3 372.45 Total cost / week 1431 3089 2607 KI (2006) 70, 963-968

Dialysis guideline in NTUH SICU Dominant and responsibility by Intensivist Hybrid Therapies in NTUH SICU Setting up and performing by Technician and NP

Guideline in CVVH Indication： Setting: (1). Cerebral edema：Mannitol ≧ q12hr in use frequency (2). Prevention of post-dialytic “ rebound” intoxication Setting: Double lumen: 14Fr，儘量打在right neck vein blood flow: 200mL/min hemofiltration: 35mL/kg/hr dialyzer: PAN 10 HF-400 CVVH：pre-dilution : post-dilution＝ 50%:50% Replacement fluid：信東A＋(B＋Rolikcan)，若病人「K+」低，則每袋B液加KCl (20 meq)一支

Guideline in IHD (1). IHD (4 hr)：病況穩定時使用之 (2). EDD (4 ~ 6hr)：stable hemodynamics，但預計脫水超過2L，為了增加脫水量而延長H/D時Initial H/D setting for patients with double lumen Blood Flow：200c.c/min Dialyzer：FK-18C (EVAL 1.8m2) Dialysate：IHD、EDD set 500c.c/min，SLEDD set 300c.c/min Net UF rate: max 500c.c/hr, 若須更多的脫水，則延長透析時間 (EDD) Dialysate Temp.：37℃ Dialysate：信東No 9＋GB solution

Guideline in SLEDD、 SLEDD-f Indication: 取代CVVH blood flow: 200mL/min Dialysate: 300mL/min，Dialysate Temp. : 38℃ Portable RO機使用 Dialyzer: FX60 (FMC, Helixone 1.4m2) Duration：8 ~ 12hr Replacement fluid：UF rate : 35c.c/kg/min Dialysate：信東No 9＋GB solution

Guideline in heparin use Priming solution：2000 unit/1000c.c N/S 以下情況不用Heparin： Major operation  48 hr Bleeding tendency：INR＞2.0 or PTT > 50sec or Plat  50000 Active bleeding：e.g. GI bleeding, Surgical bleeding, etc 其他情形使用heparin Heparin solution concentration: 2c.c heparin (10000 unit)/20c.c N/S Dosage：30 unit/Kg/hr H/D結束前1小時，停止Heparin infusion Reference: Journal of Nephrology 2003:6;566-571

SLEDD-f

新型洗腎機:5008