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 ID: 402110
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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
DefinitionSlide2
Indications
In general:Severe acid-base disordersSevere electrolyte abnormalitiesRefractory volume overloadUremiaIntoxicationsIntensive Care Severe septic shockSlide3
Why CRRT?
Reduces hemodynamic instability preventing secondary ischemiaPrecise Volume control/immediately adaptableUremic toxin removalEffective control of uremia, hypophosphatemia, hyperkalemiaAcid base balance Rapid control of metabolic acidosisElectrolyte management Control of electrolyte imbalancesManagement of sepsis/plasma cytokine filterSlide4
CRRT Circuit
Vascular accessBlood flows MachineryDialyzer Circuit volumeDialysate/ replacement fluid ratesAnticoagulationSlide5
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 placeSlide6
Vascular Access
PrinciplesVessel(s) and catheters should be large enough to permit blood flow rates > 300 mls/minProblemsPoor flow (high positive/negative pressures)BleedingClottingInfectionVenous stenosisSlide7
Recirculation
Access recirculation may limit clearancesSubclavian 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.Slide8
Mechanisms of Solute Removal
DiffusionUltrafiltrationDiffusion + UltrafiltrationAdsorbtionSlide9Slide10
Ultrafiltration
Pressure
Membrane
Uf
Uf
The transfer of solute in a stream of solvent, across a semi-permeable membrane, mediated by a hydrostatic force
Membrane
Coffee maker analogy of
Ultrafiltration
Removal of large volumes of solute and fluid via convectionSlide11
Solute clearance
Membrane
Blood
Dialysate/UltrafiltrateSlide12
Convective solute clearance
Membrane
Blood
UltrafiltrateSlide13
Convective solute clearance
Membrane
Blood
UltrafiltrateSlide14
Convection
: The movement of solutes with a water-flow, “solvent drag”, the movement of membrane-permeable solutes with ultra filtered waterBlood InBlood Out
to waste
(from patient)
(to patient)
HIGH PRESS
LOW PRESSSlide15
SCUF
Slow Continuous Ultrafiltration
Access
Return
Effluent
Fluid removal
Minimal solute clearanceSlide16
SCUF
CVVH
Replacement fluid
Removal
of large volumes of solute and fluid via convection
Replacement of excess UF with sterile replacement fluid
Convective solute clearanceSlide17
CVVH
Continuous Veno-Venous Hemofiltration
Access
Return
Effluent
Replacement
Fluid removal
Fluid replacement
Solute clearance
Convection
Minor amount diffusionSlide18
Extracorporeal Clearance
Hemofiltration clearance (ClHF = Qf x S)
Q
f
=
Ultrafiltration
rate
S =
Seiving
coefficient
Hemodialysis
clearance (
Cl
HD
=
Q
d
x
S
d
)
Q
d
=
Dialysate
flow rate
S
d
=
Dialysate
saturation
Hemodialfiltration
clearance
Cl
HDF = (
Qf x S) + (
Qd x S
d)Slide19
Sieving Coefficient (S)
Capacity of a solute to pass through the hemofilter membrane
S =
C
uf
/ C
p
C
uf
=
solute
concentration
in the
ultrafiltrate
C
p
=
solute
concentration
in the plasma
S = 1 Solute freely passes through the filter
S = 0 Solute does not pass through the filter
Slide20
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 coefficient
Ratio of solute concentration in ultrafiltrate to solute concentration in blood Slide21
Determinants of Sieving Coefficient
Protein bindingOnly unbound drug passes through the filterProtein binding changes in critical illnessDrug membrane interactionsAdsorption of proteins and blood products onto filter
Related to filter age
Decreased efficiency of filterSlide22
Relationship Between Free Fraction (
fu) and Sieving Coefficient (S)Slide23
Principles of Hemodialysis
Solute clearance by diffusionSuitable for removal of small molecules, and most middle moleculesSlide24
Dialysis
The use of diffusion (dialysis fluid) to achieve clearanceSlide25
Diffusive solute clearance
Membrane
Blood
DialysateSlide26
Diffusive solute clearance
Membrane
Blood
DialysateSlide27
Counter current flow
Membrane
Blood
DialysateSlide28
Dialysate Out
Dialysate InBlood InBlood Out
to waste
(from patient)
(to patient)
HIGH
CONCENTRATION
LOW
CONCENTRATIONSlide29
CVVHD
Continuous Veno-Venous Hemodialysis
S
Access
Return
Effluent
Fluid removal
Solute removal
(
small molecules)
Counter-current dialysis flow
Diffusion
Back filtration
DialysateSlide30
Dialysate
Saturation (Sd) Sd = Cd
/ C
p
C
d
=
solute
concentration in the
dialysate
C
p
=
solute
concentration
in the plasma
Decreasing
dialysate
saturation
Increasing molecular weight
Decreases speed of diffusion
Increasing
dialysate
flow rate
Decreases time available for diffusion
Slide31
Dialysate Saturation (S
d)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
flowSlide32
Replacement Fluid/Dialysate
Must contain:SodiumCalcium (except with citrate)Base (bicarbonate, lactate or citrate)May contain:PotassiumPhosphateMagnesiumSlide33
CRRT Set up
The Machine….Slide34
CVVHDF
Continuous Veno-Venous Hemodiafiltration
Replacement
S
Access
Return
Effluent
Dialysate
Fluid removal
Solute removal
(
small and larger solutes)
Diffusion plus ConvectionSlide35
Blood Flow/Blood Pump Speed
Range from 10 to 450 ml/minAverage 125-150 ml/minHigher blood flow could decrease filter clottingFactors affecting QB : - Catheter lumen size -
Blood viscosity
Slide36
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.Slide37
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 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.Slide38
Anticoagulation options
None (- if marked coagulopathy)Unfractionated heparinLMW HeparinCitrateDirect Thrombin Inhibitorsr-Hirudin Argatroban Prostacycline
Assessment:
Need ongoing anticoagulation
Risk of bleeding with heparin
2% per day
3.5-10% of deaths
25% of new hemorrhagic episodesSlide39
Impact of filter clotting
Decrease in dialysis doseWasted nursing timeIncrease in costSlide40
Renal Replacement Therapy Dose
Dose = amount of solute clearanceModifications required based on:Patient weightInterruptionsRecirculationSlide41
Dosage Adjustments in CRRT
Loading doses Loading dose depends solely on volume of distributionMaintenance dosesStandard reference tablesBase 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/minSlide42
Dosage Adjustments in CRRT
Frequent blood level determinationsAminoglycosides, vancomycin Reference tablesBennett's tables or the PDR recommendations require an approximation of patient's GFRUsing 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/minSlide43Slide44
Drug Removal During CRRT
Limited to case reports or series of patientsDifferent filter brands, sizes, flow rates
Limited information in many
reports
Artificial
models and predictions have no clinical valueSlide45
< MW = > Elimination
> Blood flow = > Elimination
>
Dialysate
flow = > Elimination
Free available drugSlide46
< VD = > Elimination
> Water solubility = > EliminationSlide47Slide48Slide49Slide50
TOXOKINETICS
MORE THAN OUTCOMESSlide51
Ongoing dilemas in CRRT
ModeClinically still part of the debate (sepsis vs. ARF)DoseRonco TrialRenal StudyATN TrialHigh Volume UltrafiltrationIHD vs CRRTNo diference in outcome in a RCTAnticoagulationSlide52
World practiceHVUF
Ongoing dilemas in CRRTSlide53