hemodialysis part i - bvn - sbnbvn-sbn.be/downloads/nephrology_core_b meijers.pdf · • ‘free’...
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HEMODIALYSIS part I
Principles, techniques, materials and quality control
Björn Meijers
• Introductory history of dialysis
• Diffusion, theoretical and practical considerations
• Filtration, theoretical considerations
• Filtration, practical considerations
• Urea kinetics
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• Introductory history of dialysis
• Diffusion, theoretical and practical considerations
• Filtration, theoretical considerations
• Filtration, practical considerations
• Urea kinetics
A brief history of dialysis
John Jacob Abel, 1857-1938
John Hopkins University
• Study of blood constituents
• Isolation of epinephrine
• Crystalisation of insulin
• Tool:
• semi-permeable membrane
(Celloidin)
• Saline solution
• Hirudoid anticoagulation
• Application:
• Blood purification
• ‘vividiffusion’
A brief history of dialysis
Georg Haas (1886 – 1971)
Giessen, Germany
‘Blood washing’
•Tool:
• semi-permeable membrane
Collodium
• Saline solution
• Heparin anticoagulation
No survival benefit
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A brief history of dialysis
Jan Kolff (1911 – 2009)
Groningen, the Netherlands
Dialysis
• Tools:
• semi-permeable membrane
Cellulose
• Saline solution
• Heparin anticoagulation
• Increased blood volume
Survival benefit
A brief history of dialysis
Kolff’s rotating drum kidney
A brief history of dialysis
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Dialysis membranes
Kolff-Graham kidney
• 1956
• Disposable
• Priming volume 1.2 – 1.4 L
• Price $59.00
Dialysis membranes
Kiil kidney (1960)
Priming volume 300 mL
Dialysis membranes
Capillary kidney (1964-1967)
Cellulose Acetate
Capillary kidney (1977-1978)
Cuprophane
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A brief history of dialysis
• Introductory history of dialysis
• Diffusion, theoretical and practical considerations
• Filtration, theoretical considerations
• Filtration, practical considerations
• Urea kinetics
Diffusion theories
Adolf Fick, 1829-1901
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Diffusion theories
Albert Einstein, 1879-1955
• Blood
• Access to blood compartment
• Anticoagulation procedures
• Hemodynamics
• Dialysis membrane
• Shape
• Diffusion characteristics
• Blood compatibility
• Dialysate
• Composition
• Anorganic and organic impurities
• Microbial contamination
Diffusion in dialysis
Dialysis membranes
Kolff-Graham Kiil Capillary
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Diffusion hollow fiber
Relative concentration
0 1
Blood inlet
Dialysate outlet
Blood outlet
Dialysate inlet
Clearance concept
Relative concentration
0 1
Blood inlet
Dialysate outlet
Blood outlet
Dialysate inlet
= C0
Cend
Reduction ratio (RR)
RR = (C0 - Cend) / C0
Clearance
Kd = RR ∙ Qb
Plasma
(1 – hematocrit)
Erythrocytes
Plasma water
(93% of plasma)
RBC water
(72% of RBC)
Blood is a complex solution…
Effects of blood characteristics
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blood water urea clearance
Plasma water
(93% of plasma)
RBC water
(72% of RBC)
Blood urea nitrogen / urea
• Measured as plasma concentration
• ‘Free’ diffusion in/ out of RBC
• Blood water flow rate
= (0.93 ∙ (1 – Hct) + 0.72 ∙ (Hct)) ∙ Qb
≈ 0.9 ∙ Qb
• Blood water urea clearance
≈ 0.894 ∙ K
blood water clearance
Plasma water
(93% of plasma)
RBC water
(72% of RBC)
Blood creatinine and phosphorus
• Measured as serum concentrations
• ‘hindered’ diffusion in/ out of RBC
• Blood water flow rate
= (0.93 ∙ (1 – Hct) + 0.72 ∙ (Hct)) ∙ Qb
≈ 0.9 ∙ Qb
• Increasing hematocrit reduces mass
removal of creatinine and phosporus
• Effectsize up to more than 10%
Effects of blood characteristics
Effect of blood flow on Clearance
• Theoretical : K = RR ∙ Qb
• In reality :
Depner,
Hemodial Int 2005
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Membrane characteristics
KoA: Dialyzer Mass Transfer Area Coefficient
• Maximum possible clearance
- of a given dialyzer (clearance Ko mutiplied with area A)
- at infinitely large blood flow rate
- at infinetely large dialysate flow rate
• Units: mL/min
• Kd can be estimated from KoA, Qb and Qd
• Nomograms allow for rapid estimation of Kd
• Practical use in the clinics is limited
(most modern membranes have high KoA)
Membrane characteristics
KoA K
(Qb 200 ml/min)
K
(Qb 400 mL/min)
% change K
400 137 173 + 26 %
800 166 235 + 42%
Depner, Hemodial Int 2005; Daugirdas et al., Handbook of dialysis, 4th edition
Membrane characteristics
Case 1 Your team performs dialysis at the ICU. The intensivist suggests that
‘you need to learn how to dialyse your patients’ as the urea reduction
ratio is not satisfying.
Review of the previous dialysis session:
• No significant issues with vascular access
• Qb 200 mL/min, Qd 500 mL/min
• Filter (manufacterer X), membrane area 1,4 m², KoA 850 mL/min
You are allowed to change one factor (excluding dialysis time). What
would have the most profound effect on the urea reduction ratio?
1. Increase membrane area (KoA)
2. Increase blood flow (Qb)
3. Increase dialysate flow (Qd)
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‘The rule of thumb..’
Courtesy of GAMBRO Lundia
Urea diffusion vs. uremia
Urea clearance (mL/min)
140 278 (FX 1000)
‘From the beginning all dialysis systems were and are designed
as urea removal machines’
TW. Meyer, Stanford University 2009
Urea diffusion vs. uremia
A. Babb, R. Popovich, G. Cristopher and B. Scribner
‘For a number of years we have been speculating that so-called “middle
molecules” play an important role in the toxicity of uremia. By middle
molecules we mean molecules that because of their size are very slowly
dialyzable when compared to urea. This very low dialyzability is due almost
entirely to a very high membrane diffusion resistance…’
Trans Am Soc Artif Organs, 1971
Water-soluble toxins
Potassium
Urea
Creatinin
Large molecules/proteins
β2-microglobulin
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Urea diffusion vs. uremia
Urea diffusion vs. uremia
Sieving coefficient ≠ diffusive clearance !
Courtesy of Fresenius
Diffusion principles
• Solutes can be removed by diffusion
• Diffuse removal can save lifes
• Removal can be quantified as clearance
• Factors determining clearance are
• Blood flow and composition
• Membrane characteristics (KoA, sieving coefficient)
• Dialysate flow
• Relative clearance is determined by laws of physics
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From diffusion to filtration
From diffusion to filtration
Osmotic gradient using hypertonic dialysate
Ventouri-type syphon
at effluent line
Pressure cooker
From diffusion to filtration
Pressure
Pressure UF
Kuf = Ultrafiltration coefficient
= dependent on membrane characteristics
= permeability of membrane to water
= volume / time ∙ pressure
Units = mL of fluid / hour ∙ mmHg
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Hemodynamics
Courtesy of GAMBRO Lundia
Hemodynamics
Courtesy of GAMBRO
Hemodynamics
1. Arterial pressure
2. Systemic pressure
(pre-filter pressure)
3. Venous pressure
Courtesy of GAMBRO
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Hemodynamics
Hemodynamics
Pressure alarms (approximative)
1. Arterial pressure < - 200 mmHg
2. Systemic pressure > 400 mmHg
(pre-filter pressure)
3. Venous pressure > 200 – 250 mmHg Courtesy of GAMBRO
Hemodynamics
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Hemodynamics
Jean Louis Poiseuille
1797 - 1869
Pressure loss
Pressure loss
Pressure
Blood Inlet
Pressure
Dialysate outlet
Pressure
Blood Outlet
Pressure
Dialysate inlet
Ultrafiltration
Ultrafiltration
TMP = Trans-Membrane Pressure
= calculated by dialysis monitor
= dependent on hemodynamics (vascular access)
= dependent on hardware (which pressure sensors available)
= dependent on used definitions
= differs between suppliers and between models
Units = mmHg
UF = TMP ∙ Quf
→ effect Δ TMP on UF depends on Quf
→ If Quf is high: TMP-regulated UF is difficult
→ Dialysis monitors don’t ‘know’ Quf
ULTRAFILTRATION CONTROL (using balance chambers)
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TMP calculations
Ultrafiltration
Backfiltration
High Quf ≈ Backfiltration
High Quf ≈ Need for pure(r) dialysate
From ultra- to hemofiltration
Daugirdas et al., Handbook of dialysis, 4th edition
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From ultra- to hemofiltration
SOLVENT DRAG
Hemofiltration
Plasmafiltration
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pre-dilution
Outflow filtrate
Outflow blood
Inflow blood
Hemofiltration
Hemofiltration
Predilution ≈ reducing serum concentrations
≈ reducing small solute clearance
(differential effect on protein-bound solutes)
post-dilution
Outflow filtrate
Outflow blood
Inflow blood
Hemofiltration
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Plasma water
(93% of plasma)
RBC
Hemofiltration
Plasma water
RBC
Hematocrit 30 % Hematocrit 37 %
Filtration 30% of
plasma water
Hemodynamics
20%
30%
40%
50%
60%
70%
0 20 40 60 80 100 120 140 160
ultrafiltration, ml/min
he
ma
toc
rit
at
dia
lyze
r o
utl
et
Hemodynamics
Jean Louis Poiseuille
1797 - 1869
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Hemofiltration in the past…
Courtesy of Lee Henderson, 2000
pre-dilution
Outflow filtrate
Outflow blood
Inflow blood
From HF to HDF
Inflow dialysate
post-dilution
Santoro A et al. Nephrol. Dial. Transplant. 2007;22:2000-2005
© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights
reserved. For Permissions, please email: [email protected]
Middilution HDF
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Filtration principles
• Ultrafiltration depends on pressure differences
• Ultrafiltration depends on membrane Quf
• Filtration removes solutes by solvent drag
• Postdilution is limited due to hemoconcentration
• Predilution is ‘unlimited’, but less effective (dilution)
Materials
• Dialysate
• Composition
• Anorganic and organic impurities
• Microbial contamination
• Dialysis membrane
• Sterility
• Materials and blood compatibility
• Dialysis monitors
Materials
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Relative concentration
0 1
Blood inlet
Dialysate outlet
Blood outlet
Dialysate inlet
Dialysate composition
Relative concentration
0 1
Dialysate composition
Blood composition
mmol/l
Na+ 135 – 145
K+ 3,5 – 5
Cl- 98 – 107
HCO3- 22 - 28
Ca2+ 1,1 – 1,3
P 0,74 – 1,52
Mg2+ 0,65 – 1,05
mg/dL
Glucose 65 – 100
Dialysate composition
mmol/l
Na+ 130 - 150
K+ 0 - 3
Cl- 109
HCO3- 20 - 40
Ca2+ 1,0 – 1,75
P 0
Mg2+ 0,5
mg/dL
Glucose 100
Dialysate preparation
Sodium, chloride,
calcium, magnesium,
potassium, sugar, …
Water..
‘Leuvens stadswater’
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Dialysate is electrolytes…
Dialysate is electrolytes…
23 kg 2,5 kg
Dialysate is electrolytes…
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NaCl NaHCO3
110 mEq Na ( = 12 mS )
140 mEq Na 30 mMol HCO3
( = 14 mS )
1:400
1,25 ml/Min
Dialysate is electrolytes…
Conductivity/ Conductance
• Measure of electricity conduction
• Movement of electrolytes (charged atoms)
• SI unit : Siemens / meter
• Used as measurement of electrolyte composition of dialysate
Case 2 The dialysis nurse comes to see you and tells you that the dialysis
monitor gives the alarm: ‘Low conductivity’
He/she asks if it’s OK to override the alarm?
Dialysate is electrolytes…
Dialysate is electrolytes + H20
Tap Water
• is the basis of the dialysate
• cannot be used directly due to contaminants
• is centrally prepared and distributed
Reverse osmosis (semi-permeable membrane)
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CONTAMINANT mg/L Calcium 2
Magnesium 4
Potassium 8
Sodium 70
Antimony 0,006
Arsenic 0,005
Barium 0,10
Beryllium 0,0004
Cadmium 0,001
Chromium 0,014
Lead 0,005
Mercury 0,0002
Selenium 0,09
Silver 0,005
Aluminium 0,01
Chloramines 0,10
Free chlorine 0,50
Copper 0,10
Fluoride 0,20
Nitrate (as N) 2,0
Sulphate 100
Thallium 0,002
Zinc 0,10
CONTAMINANT mg/L Calcium 2
Magnesium 4
Potassium 8
Sodium 70
Antimony 0,006
Arsenic 0,005
Barium 0,10
Beryllium 0,0004
Cadmium 0,001
Chromium 0,014
Lead 0,005
Mercury 0,0002
Selenium 0,09
Silver 0,005
Strontium 0,01
Aluminium 0,01
Chloramines 0,10
Free chlorine 0,50
Copper 0,10
Fluoride 0,20
Nitrate (as N) 2,0
Sulphate 100
Thallium 0,002
Zinc 0,10
CONTAMINANT mg/L
Calcium <2
Magnesium <2
Potassium <2
Sodium <50
Antimony -
Arsenic -
Barium -
Beryllium -
Cadmium -
Chromium -
Lead -
Mercury <0,001
Selenium -
Silver -
Aluminium < 0,01
Chloramines -
Free chlorine <0,1
Copper < 0,01
Fluoride <0,20
Nitrate (as N) <2,0
Sulphate <50
Thallium -
Zinc <0,10
Heavy metals <0,1
Chloride <50
ISO 23500 draft (2004) AAMI RD52 (2004)
Ph Eur 5th ed 2005 CHEMISTRY
Dialysate water and H(D)F
DIALYSATE WATER ≠ SUBSTITUTION FLUID
Glorieux et al, Nephrol Dial Transplant 2012
TGEA R 2 A TSA
INCUBATION: 7 days at 17 – 23°C
5,6 x 103 CFU/ml 5,1 x 102 CFU/ml 1,7 x 102 CFU/ml
Colony Forming Units (CFU)
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Endotoxin
Cell wall
Gram negative
Bacteria
• Structural part of the cell outer membrane
• Gramnegative bacteria
• Size: 1200 Dalton to whole cell
• Chemistry: Fat (Lipid A) and carbon hydrate
• Different species – Different Activity
Endotoxin units
Limulus Amoebocyte Lysate (LAL) test
Hemocyaninin
Limulus polymephus LAL reagens Sample (+ dilutions)
1 hour incubation
Degree of clotting
Reporting
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Dialysate water and H(D)F
Glorieux et al, Nephrol Dial Transplant 2012
Sterility Assurance Level (SAL)
A SAL of 10-6 denotes a probability of not more than one viable
microorganism in 1 000 000 sterilized items of the final product
SAL of 10-6/mL equals ...
•1 CFU per 1 000 000 ml
• Dialysate use/session is around 100 liters and more in HDF...
• One session is at least 100 000 ml
• Maximum 10 sessions without risk of bacterial contamination
Case 3 You are the treating physician responsible for a hemodialysis unit with
106 patients. The test results of the dialysate water screening arrive:
198 CFU/mL, LAL test 0,5 units/mL; What would be your action?
a) Close the unit and send the patients to another unit nearby
b) Await the next screening results
c) Something else…
Dialysate water and H(D)F
Ultrapure dialysate in perspective
Glorieux et al, Nephrol Dial Transplant 2012
Stop HDF/ high flux HD
Use low flux HD membranes only
Thorough disinfection / sterilisation
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Dialyzer membranes
Courtesy of Vienken, Fresenius Medical Care
Dialyzer membranes
Courtesy of Vienken, Fresenius Medical Care
Dialyzer membranes
Courtesy of Vienken, Fresenius Medical Care
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Dialyzer membranes
Courtesy of Vienken, Fresenius Medical Care
Dialyzer membranes
Courtesy of Vienken, Fresenius Medical Care
Dialyzer membranes
Dialyzer choice considerations
• (High KoA vs. Low KoA)
• High flux vs. Low flux
• Membrane surface area
• Mode of sterilisation (EthO vs. Steam vs. Radiation)
• (Material and biocompatibility)
• (Cost)
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Dialysis monitors
Dialysis monitors
• Hemodynamics: Qb, Pa, Pv, Psyst, TMP
• Dialysate preparation: pipette system, dry concentrate, central distribution
• Substitution solute preparation: ultrapure dialysate
• Ultrafiltration volume control
• Hemodialysis vs. Hemofiltration vs. Hmeodialfiltration (pre/post)
• Single ‘needle’ vs. Double ‘needle’
+ Blood volume monitor
+ Clearance measurements
+ ….
Dialysis monitors
Dialysis monitors
• Class IIb biomedical device (EEC directive 93/42)
• Software connections also are Class IIb biomedical devices
Materials
• Dialysate is composed of electrolytes, sugar and water
• Water purification system as ‘heart of the dialysis unit’
• Dialysate quality monitoring systems (bacteriological and anorganic)
• Choice of dialyser membrane
• Dialysis monitoring is class IIb biomedical device
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Quality control
How do you know you are deliviring good dialysis quality?
• Kt/V as measurement of urea removal
• Limitations of Kt/V
Clearance concept
Relative concentration
0 1
Blood inlet
Dialysate outlet
Blood outlet
Dialysate inlet
= C0
Cend
Reduction ratio (RR)
RR = (Cend - C0) / C0
Clearance
Kd = RR ∙ Qb
A: Volume 40L Cin
Cout
Reduction ratio (RR)
RR = (Cin - Cout) / Cin = 1
Clearance
Kd = RR ∙ Qb = Qb
Qb = 10 L / uur
Urea kinetics
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A: Volume 20L Cin
Cout
Reduction ratio (RR)
RR = (Cin - Cout) / Cin = 1
Clearance
Kd = RR ∙ Qb = Qb
Qb = 10 L / uur
Kt/V = 10 * 2 / 40 = 0.5
B: Volume 20L
Urea kinetics
Cin
Cout
Reduction ratio (RR)
RR = (Cin - Cout) / Cin = 1
Clearance
Kd = RR ∙ Qb = Qb
Qb = 10 L / uur
After 4 hours
Kt/V = 10 * 4 / 40 = 1.0
Volume A contains no solutes B: Volume 40L
A: Volume 0L
Urea kinetics
A: Volume 40L Cin
Cout
Reduction ratio (RR)
RR = (Cin - Cout) / Cin = 1
Clearance
Kd = RR ∙ Qb = Qb
Qb = 10 L / uur
After 4 hours
Kt/V = 10 * 4 / 40 = 1.0
Volume A = 40 L
Volume A contains solutes!
Mathematical (single pool)
spKt/V = - Ln (1 – RR)
Urea kinetics
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Urea kinetics
Daugirdas et al., Handbook of dialysis, 4th edition
Urea kinetics
Daugirdas et al., Handbook of dialysis, 4th edition
Urea kinetics
Daugirdas et al., Handbook of dialysis, 4th edition
Suggested self-study and hemodialysis core curriculum part II
• Equilibrated Kt/V
• Correction for urea generation during dialysis
• Correction for volume removal (reduction of V)
• Correction for residual renal function
• Standardized Kt/V
• Calculation of urea distribution volume
• Protein nitrogen appearance