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CRRT .pdf
1. CRRT
Continuous Renal Replacement Therapies
and associated techniques
Give definitions related to CRRT and
associated therpapies
associated therpapies
Introduce the concepts of CRRT
Discuss some of the existing scientific
publications
Discuss CRRT practical aspects
2. “Any extracorporeal blood purification
therapy intended to substitute for impaired
renal function over an extended period of time
CRRT definition
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
4. CRRT terms
C: Continuous
CRRT is intended to be applied 24/24 hours, 7 days per week
R: Renal
CRRT is applied in case of renal failure (normally acute)
R: Replacement
CRRT intends to replace the kidneys excretion and acid-base
regulation functions
T: Therapy
CRRT is a therapeutic tool for ICU patients with ARF (AKI)
5. History of CRRT
1977, Kramer et al describ a therapy named CAVH
(continuous arteriovenous hemofiltration) where the
blood is moved from an artery to a vein through a
hemofilter. Ultrafiltration rate is controlled by
raising and lowering the drain bag.
raising and lowering the drain bag.
Because of hypotension experienced by critically ill
patients the blood flow of AV methods is low and
limits the volume of ultrafiltrate that can be obtained.
The connection of the blood line to a patient ’s artery
presents major risks.
6. History of CRRT
1980, blood pump and a double-lumen catheter
in a large vein are used to provide a consistent
blood, and thus ultrafiltrate, flow.
This venovenous technique has been since then
This venovenous technique has been since then
been adopted and improved as the most
standard CRRT
90 ’s the first fully automatic machines are
designed
7. CRRT in the 80 ’s
Pumps for fluid balance
Blood pump
Blood warmer
8. CRRT in the 90 ’s and 2000
90 ’s : 2 modules, 1 for blood
circulation and 1 for fluid
exchange
2000 :
All elements are
integrated in the
same machine
9. History of CRRT
Since 2000, technology is improved
- to allow higher flows
- perform new therapies such as CPFA
- reduce the number of adverse events
2002, ADQI group gives the first consensus
definition of ARF (Acute Renal Failure), the
main reason to perform CRRT
10. ADQI Aims
Acute Dialysis Quality Initiative
The intent of ADQI is to provide an objective,
dispassionate distillation of the literature and
description of the current state of practice of acute
description of the current state of practice of acute
dialysis and related therapies.
The purpose is to develop a consensus of opinion,
with evidence where possible, on best practice and
to articulate a research agenda to focus on
important unanswered questions.
12. ADQI Methodology
Pre-meeting:
Lit search/review
Breakout groups
3-5 experts/topic
Compile evidence
and evaluate current
state of agreement
Present to
Revise as
Draft final Present to
Entire Group
Revise as
necessary
Draft final
statements
Summary Statements
Clinical Practice
Recommendations
For ARF Research
13. The Need for Defining ARF
Acute renal failure occurs in 5-20% of critically
ill patients with a mortality varying from 28
to 90%.
to 90%.
At least 30 definitions of ARF are in use !
Conclusion:
We have no idea what ARF is !
14. R
2
= 0.3962
p = 0.007
50%
60%
70%
80%
Mortality
Definitions of ARF directly
impact on measured mortality
0%
10%
20%
30%
40%
1 1.5 2 2.5 3 3.5 4 4.5
Definition Grade
Mortality
Kellum et al. Current Opin in Crit Care 2002
15. Acute Renal Failure :
Time for Consensus
Pragmatic and Practical Definitions of ARF
Solute clearance (Serum Creatinine; perhaps BUN)
Urine Output
Not unlike ARDS/ALI
Not unlike ARDS/ALI
Infiltrates on Chest X-ray
PO2:FIO2 relationship (confounded by PEEP etc)
Not unlike Severe Sepsis
Infection plus Organ Failure not always causal
Bellomo et al. Intensive Care Med 2001
16. RIFLE Criteria for Acute Renal Dysfunction
Risk
Injury
Increased creatinine x1.5
or GFR decrease > 25%
GFR Criteria Urine Output Criteria
UO < .5ml/kg/h
x 12 hr
UO < .5ml/kg/h
x 6 hr
Increased creatinine x2
or GFR decrease > 50%
Increase creatinine x3
Failure
Loss
ESRD End Stage Renal Disease
UO < .3ml/kg/h
x 24 hr or
Anuria x 12 hrs
Increase creatinine x3
or GFR dec >75%
or creatinine ≥4mg/dl
(Acute rise of ≥0.5 mg/dl)
Persistent ARF = complete loss of
renal function > 4 weeks
17. Validation of Rifle criteria
Situation in 2006
Demonstration is done that RIFLE levels influence
patients outcome.
For example :
(Bell & al, Nephrol Dial Transplant (2005)
247 patients, Mortality rates are :
Risk : 38.3%, Injury : 50%, Failure : 74.5%
Remain updated by visiting : www.ADQI.net
18. Why CRRT ?
CRRT, and in particular CVVH closely mimic the
native kidneys
CRRT is slow, gentle and well tolerated by
hypotensive patients
hypotensive patients
CRRT can remove large amounts of fluid and waste
products over time
CRRT is well tolerated by the hemodynamically
unstable patients
19. CRRT competitors
Therapies competing with CRRT are intermittent,
lasting from 4 to 12 hours per 24 or 48 hours.
The most common competitor is IHD run in 4 hours
as on chronic patients. However due to side effects
as on chronic patients. However due to side effects
it cannot be applied to all situations, in particular at
the beginning of the treatment
A reasonnable approach is 8-12 hemofiltration on
volumes equivalent to those of CRRT
20. CRRT Goals
Replace renal excretion for molecules (urea,
creatinine…) and water
Maintain electrolyte and acid/base balance
Maintain electrolyte and acid/base balance
Prevent further damage to kidney tissue and
thus improve renal recovery
Allow fluid and nutritional support
21. Neurological monitoring
The critically ill patient in ICU
Respiratory failure
requesting mechanical
ventilation
Heart failure requesting
monitoring and support
of drugs
ventilation
Nutritional assistance by
enteral and/or parenteral
feeding
Renal failure
managed by CRRT
… + temperature management,
infection treatment, blood gas
handling ...
23. Small volumes of water
removal without substitution
In case of heart failure
SCUF
Slow Continuous Ultrafiltration
In case of heart failure
Blood flow : 20-100 ml/min
UF flow : 0-2 l/h
24. Water, small and medium molecules
removal with substitution in pre
and/or post-dilution
In case of acute renal failure
CVVH
Continuous VenoVenous Hemofiltration
In case of acute renal failure
Blood flow : 80-250 ml/min
Exchange flow : 1-4 l/h
Note : CVVHD and CVVHDF are comparable to
CVVH but less efficient for medium size molecules.
25. Plasma removal and
replacement by albumine
solution or « healthy » plasma
TPE
Therapeutic Plasma Exchange
For immune diseases
Blood flow : 60-200 ml/min
Exchange flow : 1-4 l/h
Duration : 1-3 hours
26. Molecular weights
ionic compounds
ionic compounds
urea
urea
creatinine
creatinine
sucrose
sucrose
inulin
inulin
IL
IL-
-8
8
IL
IL-
-6
6
albumin
albumin
myoglobin
myoglobin
ß2 microglobulin
ß2 microglobulin
MEDIUM LARGE molecules
SMALL
IgG
IgG
HDL
HDL
10
10 10
102
2 10
103
3 10
104
4 10
105
5 10
106
6
ionic compounds
ionic compounds
Vit B
Vit B12
12
inulin
inulin
IL
IL-
-8
8
TNF
TNF
IL
IL-
-1
1
MW (Daltons)
MW (Daltons)
Hemofilter
Hemofilter cutoff
cutoff
IgG
IgG
IgM
IgM
LDL
LDL
Plasmafilter cutoff
Plasmafilter cutoff
27. Diseases treated by TPE
Removal of antibodies
Guillain-Barre, Myasthenia Gravis, Lambert-Eton Syn.
Goodpasture’s Syn., Transplant Rejection
Removal of immune complexes
S. Lupus Eryth., Rheumatoid Vasculitis
S. Lupus Eryth., Rheumatoid Vasculitis
Replacement of plasma deficiencies
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
28. TPE, treatment modality
1 treatment = 1-2 fold patient’s plasma volume
Plasma volume = 40-45 ml/kg so for example 2.8-3
liters for a 70 kg patient
Treatment duration is 1-3 hours
Treatment duration is 1-3 hours
Treatments are repeated depending on molecules
half-life and intravascular distribution
29. Plasma loop : removal of
inflammatory mediators
Hemofiltration loop :
small/medium molecules and
CPFA
Coupled Plasma Filtration Adsorption
small/medium molecules and
water removal
In case of severe sepsis or
septic shock
Blood flow : 60-200 ml/min
Exchange flows : 1-4 l/h
Duration : 6-10 hours
31. CPFA: Experimental Studies
In-Vitro studies
much more efficient clearance of cytokines
Animal Studies
rabbit model of LPS septic shock (Tetta C, Coupled plasma
filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med 28:1526-33,
2000)
85% survival in rabbits supported with CPFA
85% survival in rabbits supported with CPFA
80% mortality in control rabbits
Human Clinical Study (Brendolan A, Coupled plasma filtration-
adsorption technique in sepsis-associated acute renal failure: hemodynamic effects. J Am Soc
Nephrol 9:A0655, 1998)
improved hemodynamics
reduced inotrope requirements
improved monocyte responsiveness
32. Devices for CRRT
To perform CRRT the following is needed :
1 CRRT machine
1 hemofilter with high flux artificial membrane
1 pre-assembled tubing set
1 pre-assembled tubing set
1 venous access such as double lumen catheter
20-50 liters of sterile replacement fluid per day
Possibly anti-coagulant such as heparin
33. CRRT machine
A CRRT machine shall include :
- A complete blood pump with protections against air
injection and lines disconnections for all flows (0-400
ml/min)
- A complete fluid exchange system including precise
- A complete fluid exchange system including precise
fluid balance for all flows (0-10 l/h)
- A clear user inteface to ease understanding of the
ongoing process and choices for changes
- All necessary treatments (SCUF, CVVH, CPFA,
TPE) for both adults and young childrens.
35. Hemofilters for CRRT
Hemofilters shall :
- have 1-2 sqm artificial membrane (polysulfone,
polyethersulfone, polyamide)
- have luer-lock connectors to avoid leaks of
- have luer-lock connectors to avoid leaks of
biological fluids
- have a UFR (Ultrafiltration rate) of at least 50
ml/h x mmHg
37. Tubing set for CRRT
Tubing sets shall :
- exist preassembled for all therapies
- exist for small children with a maximum blood
volume of 30 ml
volume of 30 ml
- allow all flows up to 400 ml/min for blood at
reasonable pressures
38. Venous access for CRRT
Double lumen catheter design shall :
- allow necessary blood flow under acceptable
pressures (< 120 mmHg)
- be of a plastic that will not hurt once installed
- be of a plastic that will not hurt once installed
- be of a shape and provided with tools that makes
it fairly easy to implant
- be made in such a way to reduce recirculation
- be made in such a way to reduce clotting
39. Fluids for CRRT
Fluids are sterile and apyrogene and contain :
- target values of electrolytes
- a buffer such as lactate, bicarbonate or citrate (acetate
should not be used anymore)
should not be used anymore)
Fluid types are medications that must in all cases be
prescribed by the doctors.
40. Dialysate versus replacement solution
Fluid is named “dialysate” if injected in the hemofilter
on the dialysate side. Dialysate may be CE marked.
Fluid is named “replacement solution” if injected
directly in the blood in eithr pre or post-dilution.
directly in the blood in eithr pre or post-dilution.
Replacement fluid is a medication.
Both fluids can be absolutely the same.
42. Buffers
Buffers : Lactate
: Lactate
• used for dialysate and/or
used for dialysate and/or
replacement solutions 40
replacement solutions 40
mmol/L
mmol/L
•
• well tolerated
well tolerated
•
• lactate
lactate →
→ bicarbonate
bicarbonate
• hepatic failure
hepatic failure ↑
↑ lactate
lactate
•
• pre
pre-
-existing lactic
existing lactic
acidosis and tissue hypoxia
acidosis and tissue hypoxia
•
• 20 mmol/kg/day produced
20 mmol/kg/day produced
PRO
PRO CON
CON
•
• lactate
lactate →
→ bicarbonate
bicarbonate
1 mmol
1 mmol →
→1 mmol
1 mmol
•
• liver/muscle can convert
liver/muscle can convert
lactate
lactate →
→ bicarbonate at 100
bicarbonate at 100
mmol/hr
mmol/hr
•
• acceptable
acceptable ↑
↑ blood lactate
blood lactate
is 3
is 3-
-4 mmol/L
4 mmol/L
•
• convective loss of
convective loss of
bicarbonate from blood is ~
bicarbonate from blood is ~
30 mmol/L. This can
30 mmol/L. This can
contribute to a worsening
contribute to a worsening
metabolic acidosis.
metabolic acidosis.
43. Buffers : Bicarbonate
Buffers : Bicarbonate
• used in dialysate and/or
used in dialysate and/or
replacement
replacement
•
• well tolerated and most
well tolerated and most
physiologic of the buffers
physiologic of the buffers
•
• more unstable
more unstable-
- must be
must be
mixed prior to infusing
mixed prior to infusing
•
• potential for Ca and Mg
potential for Ca and Mg
precipitation
precipitation
PRO
PRO CON
CON
physiologic of the buffers
physiologic of the buffers
•
• can be used in patients
can be used in patients
with liver failure
with liver failure
•
• better control of metabolic
better control of metabolic
acidosis
acidosis
•
• preferred in patients with
preferred in patients with
lactic acidosis
lactic acidosis
precipitation
precipitation
•
• bacteremia
bacteremia-
- if left
if left
standing for more than 24
standing for more than 24
hours
hours
•
• hypernatremia
hypernatremia
44. Buffers :
Buffers : Citrate
Citrate
• anticoagulant by chelating calcium ions to produce a soluble
anticoagulant by chelating calcium ions to produce a soluble
complex in which calcium cannot be used in the clotting
complex in which calcium cannot be used in the clotting
cascade.
cascade.
•
• it is metabolized in the body within 30 minutes by the liver,
it is metabolized in the body within 30 minutes by the liver,
PRO
PRO
•
• it is metabolized in the body within 30 minutes by the liver,
it is metabolized in the body within 30 minutes by the liver,
skeletal muscle and the kidneys.
skeletal muscle and the kidneys.
•
• as a buffer. Citrate
as a buffer. Citrate →
→ bicarbonate : 1 mmol
bicarbonate : 1 mmol →
→ 3 mmol.
3 mmol.
45. • ↑
↑ Na
Na+
+ load
load →
→ hypernatremia
hypernatremia
•
• Hypocalcemia
Hypocalcemia -
- requires an infusion of CaCl
requires an infusion of CaCl
•
• Hypercalcemia
Hypercalcemia-
- with increased calcium chelate
with increased calcium chelate
CON
CON
Buffers :
Buffers : Citrate
Citrate
•
• Hypercalcemia
Hypercalcemia-
- with increased calcium chelate
with increased calcium chelate
•
• Hypomagnesemia
Hypomagnesemia
•
• Metabolic alkalosis
Metabolic alkalosis
•
• Use cautiously in patients with severe liver disease.
Use cautiously in patients with severe liver disease.
•
•Requires special fluid without Ca nor other buffer
Requires special fluid without Ca nor other buffer
46. Managing CRRT
When to start ?
Which therapy ?
Which dose ?
Preparing the machine and
patient
patient
Blood circulation
Anti-coagulation
Fluid balance
Thermal balance
Complications
47. Managing CRRT
When to start ?
There is no absolute response, however being
in the Risk or Injury zone of the RIFLE
in the Risk or Injury zone of the RIFLE
criteria might be the right way and …
don ’t forget that between decision to treat and
actual treatment hours may pass worsening
the patient ’s clinical situation
48. Managing CRRT
Which therapy ?
CVVH is the most common in Europe (70% of
the treatments) and prefferred because it is
well tolerated and removes many nephrotoxic
well tolerated and removes many nephrotoxic
medium size molecules.
If intermittent treatment is choosen it should be
daily at least until patient becomes stable
49. Managing CRRT
Which dose ?
Recommended continuous dose is 25-35
ml/kg/h. In intermittent therapies, this is
ml/kg/h. In intermittent therapies, this is
calculated 60-85% patient ’s body weight
per 24 hours.
Patients having a large part of fat or being
septic may benefit from higher doses
50. Managing CRRT
Preparing patient :
Catheter must be positionned and able to
provide expected blood flows.
Blood samples must be analysed
Blood samples must be analysed
Dose, fluid balance and anti-coagulation
protocol must be prescribed
Organisation shall allow patient to remain in his
bed for the planned duration of the therapy
52. Managing CRRT
Preparing machine :
Select tubing sets, filters and fluids adapted to
the specified protocol
Prime and rinse the system
Prime and rinse the system
Insert the treatment protocol through the
machine ’s user interface
Connect patient to machine using aseptic
methods
53. Managing CRRT
Blood circulation
Must be high enough to provide the expected
clearance
Must be with A/V pressure values below 120 mmHg
Must be with A/V pressure values below 120 mmHg
to avoid frequent stops due to overpressures
Must integrate anti-coagulants when necessary
Treatment is impossible without a correct blood
circulation
54. Anti-Coagulation
Anti-coagulation protocol is a medical decision !
Guidelines do exist that are reasonable and can be
followed
Questions to be asked :
- Can we do anticoagulation free treatment ?
- Can we do anticoagulation free treatment ?
- Will we use Heparin (systemic anti-coagulation) ?
If so which type ?
- Will we use Citrate (regional anti-coagulation)?
If so using which protocol ?
In all cases, anticoagulation protocols must be adapted to
patients current clinical situation
55. Anti-coagulation goal versus risks
Goal of anti-coagulation in RRT : is not defined !
To minimise patient ’s blood losses ? Or
Provide the best compromise between extracorporeal circuit
patency versus patient’s complications related to
anticoagulation ?
anticoagulation ?
Risk associated to anti-coagulation shall not be under-
estimated in the choice of the method to reach the goal.
Many European centers run RRT without anti-coagulation in at
least 50% of the treatments.
56. Practical aspects of anti-coagulation
The following help preventing circuit blood clotting :
- Increased blood flow
- The use of predilution
- Membrane/circuit biocompatibility (material,
configuration…)
configuration…)
The following increase risks circuit clotting :
- Low blood flow
- High filtration fraction
- Poor circuit design, i.e. entering blood from filter top
- Frequent stops of blood pump (i.e. due to access alarms)
57. Recommended pressures during CRRT
Arterial Pressure
Negative
-30 to -120 mmHg
Pre-filter pressure
Positive
+100 to +250 mmHg
Effluent pressure
Negative or Positive
Venous Pressure
Positive
+30 to +120 mmHg
Negative or Positive
Used only to calculate
the TMP
TFP = Pre-filter - Venous. Represents the clotting inside the filter
TMP = (Pre-filter + Venous) / 2 - Effluent. Represents the clogging of the membrane
58. Factors affecting A/V pressures
Individual patient characteristics
Blood pressure, size, presence of oedema, hematocrit
Location and condition of vascular access
Catheter size and type
Catheter size and type
Blood flow rate
Note : Machines are never responsible for A/V
pressure alarms.
59. Factors affecting TMP and TFP
TMP
Blood flow (too low, TMP may increase)
UF flow (too high, TMP may increase)
Predilution ratio
Filter membrane material and surface
Filter membrane material and surface
TFP
Blood flow
Blood hematocrit
Blood clotting inside the filter ’s capillaries
Capillaries dimensions and number of these inside the filter
60. Managing CRRT
Fluid balance
Must be adapted to patient ’s clinical status
Must be controlled during the whole process
Must be controlled during the whole process
and especially when machines provide
alarms indicating that an error may have
happen.
Must include all fluids in and out of the
patient.
61. Fluid balance in practice
Fluids entering the balance :
- machine fluid balance as requested and displayed
- enteral and parenteral feeding
- fluids given by externally to the machine
- drugs from syringe drivers
- drugs from syringe drivers
- natural urine output
Through scales, machines measure the fluids they
inject and those they recieve (effluent). The
difference is the fluid balance (weight change)
provided by the machine.
62. Acid/Base and electrolyte balance
Acid-base balance is reached through the fluids « strong ion
difference » (H+, CL-) (Boyle, Baldwin, Australian Critical Care, 2002)
Buffers (HCO3
-) maintain acid-base balance by neutralising
excess of strong ions
Blood electrolytes will tend to reach the values actually
Blood electrolytes will tend to reach the values actually
placed in the replacement solution / dialysate
Fluids content is the key towards acid/base and
electrolyte balance
These values must bee closely monitored during CRRT
63. Thermal balance in CRRT
Hyperthermia : safety systems limit the temperature of
injected fluids to 41 degree in all cases.
Hypothermia :
Is caused by patient’s blood circulation at room temperature
Is caused by patient’s blood circulation at room temperature
and administration of fluids colder than patient ’s
temperature
Symptoms of hypothermia are hemodynamic instability,
chilling, shivering, skin pallor, coolness and cyanosis
Hypothermia consumes patients energy !
Hypothermia can be prevented by injecting fluids that are
warmed up at 37-39 degree Celsius
64. Managing CRRT
Anti-coagulation
Is specific to patient ’s clinical condition. Is
usually prescribed according to the current
ACT or APTT values in accordance with
ACT or APTT values in accordance with
accepted recommendations.
No anti-coagulant (30-50%), heparine (30-
50%) and citrate are the most usual anti-
coagulant methods.
65. Potential complications in CRRT
Machines ultrasonic air detectors tolerate microbubbles (< 20
ul) and foam to pass which may cumulate inside the patient
and lead to air emboli.
Machines pressure sensing system may not detect all tubes
disconnection as these may be partial and with pressure
change remaining inside the accepted range
change remaining inside the accepted range
Machines blood leak detectors may not detect small amounts
(< 0.5 ml/min = 30 ml/h = 720 ml/day) of red cells leading
to cumulated blood cells.
Fluid balance errors may cumulate each time machine detect
a potential error.
+ … acid-base, thermal, anti-coagulant, electrolytes balances
must be kept within targets
