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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
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Indications In general: Intensive Care Severe acid-base disorders
Severe electrolyte abnormalities Refractory volume overload Uremia Intoxications Intensive Care Severe septic shock
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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
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CRRT Circuit Vascular access Blood flows Machinery Dialyzer
Circuit volume Dialysate/ replacement fluid rates Anticoagulation
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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
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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
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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 .
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Mechanisms of Solute Removal
Diffusion Ultrafiltration Diffusion + Ultrafiltration Adsorbtion
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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
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Dialysate/Ultrafiltrate
Solute clearance Blood Membrane Dialysate/Ultrafiltrate
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Convective solute clearance
Blood Membrane Ultrafiltrate
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Convective solute clearance
Blood Membrane Ultrafiltrate
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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
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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
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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
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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
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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
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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
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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
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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
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Relationship Between Free Fraction (fu) and Sieving Coefficient (S)
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Principles of Hemodialysis
Solute clearance by diffusion Suitable for removal of small molecules, and most middle molecules
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The use of diffusion (dialysis fluid) to achieve clearance
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Diffusive solute clearance
Blood Membrane Dialysate
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Diffusive solute clearance
Blood Membrane Dialysate
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Counter current flow Blood Membrane Dialysate
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Dialysate Out Dialysate In Blood In Blood Out to waste (from patient)
(to patient) HIGH CONCENTRATION LOW CONCENTRATION
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CVVHD Continuous Veno-Venous Hemodialysis Dialysate Access
Return Effluent Dialysate Fluid removal Solute removal (small molecules) Counter-current dialysis flow Diffusion Back filtration
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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
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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
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Replacement Fluid/Dialysate
Must contain: Sodium Calcium (except with citrate) Base (bicarbonate, lactate or citrate) May contain: Potassium Phosphate Magnesium
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CRRT Set up The Machine….
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CVVHDF Continuous Veno-Venous Hemodiafiltration
Dialysate Access Return Fluid removal Solute removal (small and larger solutes) Diffusion plus Convection Replacement S Effluent
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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
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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.
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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
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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
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Impact of filter clotting
Decrease in dialysis dose Wasted nursing time Increase in cost
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Renal Replacement Therapy Dose
Dose = amount of solute clearance Modifications required based on: Patient weight Interruptions Recirculation
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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
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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
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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
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> Blood flow = > Elimination
< MW = > Elimination > Dialysate flow = > Elimination Free available drug
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< VD = > Elimination
> Water solubility = > Elimination
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TOXOKINETICS MORE THAN OUTCOMES
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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
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Ongoing dilemas in CRRT
World practice HVUF
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