Continuous Renal Replacement Therapy (CRRT) Any extracorporeal blood purification therapy intended...
Transcript of Continuous Renal Replacement Therapy (CRRT) Any extracorporeal blood purification therapy intended...
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
Definition
IndicationsIn general:
Severe acid-base disorders Severe electrolyte abnormalities Refractory volume overload Uremia Intoxications
Intensive Care Severe septic shock
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
CRRT Circuit
Vascular accessBlood flows MachineryDialyzer Circuit volumeDialysate/ replacement fluid ratesAnticoagulation
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
Vascular AccessPrinciples
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
RecirculationAccess 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.
Mechanisms of Solute Removal
Diffusion
Ultrafiltration
Diffusion + Ultrafiltration
Adsorbtion
UltrafiltrationPressure
Membrane
UfUf
The transfer of solute in a stream of solvent, across a semi-
permeable membrane, mediated by a hydrostatic force
Membrane
Coffee maker analogy of UltrafiltrationRemoval of large volumes of solute and fluid via convection
Solute clearanceMembraneBlood Dialysate/Ultrafiltrate
Convective solute clearance
MembraneBlood Ultrafiltrate
Convective solute clearance
MembraneBlood Ultrafiltrate
Convection: The movement of solutes with a water-flow, “solvent drag”, the movement of membrane-permeable solutes with ultra
filtered water
Blood In
Blood Out
to waste(from patient)
(to patient)
HIGH PRESS
LOW PRESS
SCUFSlow Continuous
UltrafiltrationAccess
Return
Effluent
Fluid removal Minimal solute
clearance
SCUF CVVH
Replacement fluid
Removal of large volumes of solute and fluid via convectionReplacement of excess UF with sterile replacement fluid
Convective solute clearance
CVVHContinuous Veno-Venous
HemofiltrationAccess
Return
Effluent
Replacement
Fluid removal Fluid replacement Solute clearance Convection Minor amount
diffusion
Extracorporeal Clearance
Hemofiltration clearance (ClHF = Qf x S)Qf = Ultrafiltration rateS = Seiving coefficient
Hemodialysis clearance (ClHD = Qd x Sd)Qd = Dialysate flow rateSd = Dialysate saturation
Hemodialfiltration clearance
ClHDF = (Qf x S) + (Qd x Sd)
Sieving Coefficient (S)
Capacity of a solute to pass through the hemofilter membrane
S = Cuf / Cp
Cuf = solute concentration in the ultrafiltrateCp = solute concentration in the plasmaS = 1 Solute freely passes through the filterS = 0 Solute does not pass through the filter
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
Sieving coefficientRatio of solute concentration in ultrafiltrate to solute concentration in blood
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
Relationship Between Free Fraction (fu) and Sieving Coefficient (S)
Principles of Hemodialysis
Solute clearance by diffusion
Suitable for removal of small molecules, and most middle molecules
DialysisThe use of diffusion (dialysis fluid) to achieve clearance
Diffusive solute clearance
MembraneBlood Dialysate
Diffusive solute clearance
MembraneBlood Dialysate
Counter current flowMembraneBlood Dialysate
Dialysate Out
Dialysate In
Blood In
Blood Out
to waste
(from patient)
(to patient)
HIGH CONCENTRATIONLOW CONCENTRATION
CVVHD Continuous Veno-Venous Hemodialysis
S
Access
Return
Effluent
Fluid removal
Solute removal
(small molecules)
Counter-current dialysis
flow
Diffusion
Back filtration
Dialysate
Dialysate Saturation (Sd)
Sd = Cd / CpCd = solute concentration in the dialysateCp = solute concentration in the plasma
Decreasing dialysate saturation Increasing molecular weight
Decreases speed of diffusion Increasing dialysate flow rate
Decreases time available for diffusion
Dialysate Saturation (Sd)
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
Replacement Fluid/DialysateMust contain:SodiumCalcium (except with citrate)Base (bicarbonate, lactate or citrate)
May contain:PotassiumPhosphateMagnesium
CRRT Set upThe Machine….
CVVHDFContinuous Veno-Venous Hemodiafiltration
Replacement
S
Access
Return
Effluent
Dialysate
Fluid removal Solute removal (small and larger solutes)
Diffusion plus Convection
Blood Flow/Blood Pump Speed
·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
Effect of filtration on CVVH
Hematocrit30%
Hematocrit60%
A filtration fraction of more than 25 - 30% greatly increasesblood viscosity within the circuit, risking clot and malfunction.
Blood flow requirements for CRRT to maintain filtration fraction at 25%
Ultrafiltration rate (mls/hr) Minimum Qb/min
1500 100
2000 130
2500 155
3000 200
4000 265
The degree of blood dehydration can beestimated by determining the filtration fraction
(FF), which is the fraction of plasma waterremoved by ultrafiltration:FF(%) = (UFR x 100) / QP
where QP is the filter plasma flow rate in ml/min.
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
Impact of filter clotting
Decrease in dialysis doseWasted nursing timeIncrease in cost
Renal Replacement Therapy Dose
Dose = amount of solute clearanceModifications required based on:
Patient weight Interruptions Recirculation
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 < 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
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
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
< MW = > Elimination
> Blood flow = > Elimination
> Dialysate flow = > Elimination
Free available drug
< VD = > Elimination
> Water solubility = > Elimination
TOXOKINETICS MORE THAN OUTCOMES
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
World practice
HVUF
Ongoing dilemas in CRRT