Transcript Slide 1
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 In general: Severe acid-base disorders Severe electrolyte abnormalities Refractory volume overload Uremia Intoxications Intensive Care Severe septic shock 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 Vascular access Blood flows Machinery Dialyzer Circuit volume Dialysate/ replacement fluid rates Anticoagulation 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 Principles 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 Access 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 . Diffusion Ultrafiltration Diffusion + Ultrafiltration Adsorbtion Pressure Membrane Uf Membrane Uf The transfer of solute in a stream of solvent, across a semipermeable membrane, mediated by a hydrostatic force Coffee maker analogy of Ultrafiltration Removal of large volumes of solute and fluid via convection Blood Membrane Dialysate/Ultrafiltrate Blood Membrane Ultrafiltrate Blood Membrane Ultrafiltrate to waste Blood In (from patient) HIGH PRESS Blood Out LOW PRESS (to patient) Convection: The movement of solutes with a water-flow, “solvent drag”, the movement of membrane-permeable solutes with ultra filtered water SCUF Slow Continuous Ultrafiltration Access Return Fluid removal Minimal solute clearance Effluent 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 CVVH Continuous Veno-Venous Hemofiltration Access Fluid removal Fluid replacement Solute clearance Convection Minor amount diffusion Return Replacement Effluent 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) 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 Ratio of solute concentration in ultrafiltrate to solute concentration in blood 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 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 Solute clearance by diffusion Suitable for removal of small molecules, and most middle molecules Dialysis The use of diffusion (dialysis fluid) to achieve clearance Blood Membrane Dialysate Blood Membrane Dialysate Blood Membrane Dialysate to waste Dialysate Out Blood In (from patient) Dialysate In Blood Out (to patient) LOW CONCENTRATION HIGH CONCENTRATION CVVHD Continuous Veno-Venous Hemodialysis Dialysate Fluid removal Solute removal Access Return (small molecules) Counter-current dialysis flow Diffusion Back filtration S Effluent 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 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 Must contain: Sodium Calcium (except with citrate) Base (bicarbonate, lactate or citrate) May contain: Potassium Phosphate Magnesium The Machine…. CVVHDF Continuous Veno-Venous Hemodiafiltration Dialysate Access Return Fluid removal Solute removal Replacement (small and larger solutes) Diffusion plus Convection S Effluent 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 Hematocrit 60% Hematocrit 30% A filtration fraction of more than 25 - 30% greatly increases blood viscosity within the circuit, risking clot and malfunction. 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 • • • • • 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 Decrease in dialysis dose Wasted nursing time Increase in cost Dose = amount of solute clearance Modifications required based on: Patient weight Interruptions Recirculation 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 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 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 > Blood flow = > Elimination < MW = > Elimination > Dialysate flow = > Elimination Free available drug < VD = > Elimination > Water solubility = > Elimination TOXOKINETICS MORE THAN OUTCOMES 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 Ongoing dilemas in CRRT World practice HVUF