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
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In general:
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Severe acid-base disorders
Severe electrolyte abnormalities
Refractory volume overload
Uremia
Intoxications
Intensive Care
 Severe septic shock
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Reduces hemodynamic instability preventing secondary
ischemia
 Precise Volume control/immediately adaptable
 Uremic toxin removal
 Effective control of uremia, hypophosphatemia, hyperkalemia
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Acid base balance
 Rapid control of metabolic acidosis
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Electrolyte management
 Control of electrolyte imbalances
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Management of sepsis/plasma cytokine filter
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Vascular access
Blood flows
Machinery
Dialyzer
Circuit volume
Dialysate/ replacement fluid rates
Anticoagulation
Vascular Access
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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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Principles
 Vessel(s) and catheters should be large enough to
permit blood flow rates > 300 mls/min
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Problems
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Poor flow (high positive/negative pressures)
Bleeding
Clotting
Infection
Venous stenosis
Access recirculation may limit clearances
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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
.
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Diffusion
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Ultrafiltration
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Diffusion + Ultrafiltration
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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
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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
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Fluid removal
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Fluid replacement
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Solute clearance
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Convection
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Minor amount diffusion
Return
Replacement
Effluent
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Hemofiltration clearance (ClHF = Qf x S)
Qf = Ultrafiltration rate
S = Seiving coefficient
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Hemodialysis clearance (ClHD = Qd x Sd)
Qd = Dialysate flow rate
Sd = Dialysate saturation
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Hemodialfiltration clearance
ClHDF = (Qf x S) + (Qd x Sd)
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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
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 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
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Fluid removal
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Solute removal
Access
Return
(small molecules)
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Counter-current dialysis flow
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Diffusion
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Back filtration
S
Effluent
Sd = Cd / Cp
Cd = solute concentration in the dialysate
Cp = solute concentration in the plasma
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Decreasing dialysate saturation
 Increasing molecular weight
 Decreases speed of diffusion
 Increasing dialysate flow rate
 Decreases time available for diffusion
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Countercurrent dialysate flow (10 - 30 ml/min) is
always less than blood flow (100 - 200 ml/min)
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Allows complete equilibrium between blood serum
and dialysate
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Dialysate leaving filter will be 100% saturated with
easily diffusible solutes
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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
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Fluid removal
Solute removal
Replacement
(small and larger solutes)
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Diffusion plus Convection
S
Effluent
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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
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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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Decrease in dialysis dose
Wasted nursing time
Increase in cost
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Dose = amount of solute clearance
Modifications required based on:
 Patient weight
 Interruptions
 Recirculation
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Loading doses
 Loading dose depends solely on volume of distribution
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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%
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How often do I dose the drug?
 Haemofiltration: ‘GFR’ 10 - 20 ml/min
 Haemofiltration with dialysis: ‘GFR’ 20 - 50 ml/min
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Frequent blood level determinations
 Aminoglycosides, vancomycin
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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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Limited to case reports or series of patients
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Different filter brands, sizes, flow rates
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Limited information in many reports
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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
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Mode
 Clinically still part of the debate (sepsis vs. ARF)
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Dose
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Ronco Trial
Renal Study
ATN Trial
High Volume Ultrafiltration
IHD vs CRRT
 No diference in outcome in a RCT
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Anticoagulation
Ongoing dilemas in CRRT
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World practice
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HVUF