Transcript Continuous Renal Replacement Therapy (CRRT)

Dr. M.A. Al-Odat
Jordanian Board of Medicine
Saudi ICU board fellow.
WHAT
Is CRRT
WHAT HOW
To use CRRT
Is CRRT
Is an 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 a 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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Mimic the functions and physiology of the
native organ
Qualitative and quantitative blood
purification
Restore and maintain of homeostasis
Avoid complications and good clinical
tolerance
Provide conditions favoring recovery of
renal function
A central double-lumen veno-venous
hemodialysis catheter
 An extracorporeal circuit and a
hemofilter
 A blood pump and a effluent pump.
 With specific CRRT therapies
dialysate and/or replacement pumps
are required.
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CRRT is indicated in any patient who meets criteria
for hemodialysis therapy but cannot tolerate
intermittent dialysis due to hemodynamic instability.
CRRT is better tolerated by hemodynamically
unstable patients because fluid volume, electrolytes
and pH are adjusted slowly and steadily over a 24
hour period rather than a 3 – 4 hour period.
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Hemodynamically unstable patients with the
following diagnoses may be candidates for CRRT:
fluid overload
acute renal failure
chronic renal failure
life-threatening electrolyte imbalance
major burns with compromised renal function
drug overdose
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Vascular access.
Semi-permeable membrane.
Transport mechanism.
Dialysate and replacement fluid.
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Internal jugular.
Subclavian.
Femoral.
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Internal Jugular Vein
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Femoral Vein
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Primary site of choice due to lower associated risk of
complication and simplicity of catheter insertion.
Patient immobilized, the femoral vein is optimal and
constitutes the easiest site for insertion.
Subclavin Vein
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The least preferred site given its higher risk of
pneumo/hemothorax and its association with central
venous stenosis.
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The length of the catheter chosen will depend
upon the site used
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Size of the catheter is important in the pediatric
population.
The following are suggested guidelines for the
different sites:
RIJ= 15 cm French
 LIJ= 20 cm French
 Femoral= 25 cm French
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The basis of all blood purification therapies.
Water and some solutes pass through the membrane, while
cellular components and other solutes remain behind.
2 types: cellulose and synthetic.
Synthetic membranes allow clearance of larger molecules
and are the primary type used in CRRT.
Filters are changed when they become contaminated,
clogged or clotted.
(Dalton)
100000
50000
10000
5000
Albumin (55000 – 60000)
Beta 2 Microglobulin (11800)
Inulin (5200)
Vit B12 (1355)
1000
500
100
50
10
Aluminium/Desforoxamine complex (700)
Glucose (180)
Uric Acid (168)
Creatinine (113)
Phosphate (80)
Urea (60)
Potassium (35)
Phosphorus (31)
Sodium (23)
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The passage of water through a membrane under a
pressure gradient.
Driving pressure can be +ve (push fluid through the
filter), or –ve (pull fluid to other side of filter).
Pressure gradient is created by effluent pump.
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Movement of solutes through a membrane by the force of
water “solvent drag”.
The water pulls the molecules along with it as it flows
through the membrane.
can remove middle and large molecules, as well as large
fluid volumes.
maximized by using replacement fluids.
To better understand this phenomenon, think of a quiet stream as compared to
a raging river. The stream could never shift a boulder, but the powerful raging
river could easily drag a boulder downstream. So it is with convection; the
faster the flow through the membrane, the larger the molecules that can be
transported
Adsorption is the removal of solutes from the blood because they
cling to the membrane. Think of an air filter. As the air passes
through it, impurities cling to the filter itself. Eventually the
impurities will clog the filter and it will need to be changed. The
same is true in blood purification. High levels of adsorption can
cause filters to clog and become ineffective
Diffusion is the movement of a solute across a membrane via a
concentration gradient. For diffusion to occur, another fluid must flow on
the opposite side of the membrane. In blood purification this fluid is
called dialysate. When solutes diffuse across a membrane they always
shift from an area of higher concentration to an area of lower
concentration until the solute concentration on both sides of the
membrane is equal.
Dialysate is any fluid used on the
opposite side of the filter from the
blood during blood purification.
As with traditional hemodialysis
therapy, the dialysate is run on the
opposite side of the filter,
countercurrent to the flow of the
patient’s blood. The countercurrent
flow allows a greater diffusion
gradient across the entire membrane,
increasing the effectiveness of solute
removal.
Typical dialysate flow rates are
between 600 – 1800 mL/hour.
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Used to increase the amount of convective solute
removal in CRRT.
Replacement fluids do not replace anything.
Fluid removal rates are calculated independently of
replacement fluid rates.
The most common replacement fluid is 0.9%
Normal Saline.
Can be pre or post filter.
The decision to infuse replacement fluids before or
after the filter is made by the physician. Replacement
fluids administered pre-filter reduce filter clotting and
can be administered at faster rates (driving higher
convection) than fluids administered post-filter. The
downside of pre-filter replacement fluids is that they
invalidate post-filter lab draws; the lab results will
show the composition of the replacement fluid rather
than that of the effluent.
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The primary indication for SCUF is fluid overload
without uremia or significant electrolyte imbalance.
The main mechanism of water transport is
ultrafiltration.
Other solutes are carried off in small amounts, but
usually not enough to be clinically significant.
the amount of fluid in the effluent bag is the same as
the amount removed from the patient.
Fluid removal rates are typically closer to 100
mL/hour.
No dialysate or replacement fluid is used.
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Blood flow: 80 – 200 ml/min
Duration
Ultrafiltration: 20-100 ml/hr (or total volume)
Anticoagulation
NO dialysate, NO replacement fluid
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An extremely effective method of solute removal and is
indicated for uremia or severe pH or electrolyte imbalance
with or without fluid overload.
Particularly good at removal of large molecules, because
CVVH removes solutes via convection,
Many theories exist regarding the removal of proinflammatory mediators by CVVH.
solutes can be removed in large quantities while easily
maintaining a net zero or even a positive fluid balance in
the patient.
the amount of fluid in the effluent bag is equal to the
amount of fluid removed from the patient plus the volume
of replacement fluids administered.
No dialysate is used.
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Blood flow:80 – 200 ml/min
Duration
Ultrafiltration: 20-100 ml/hr (or total volume)
RF: 1000 – 2000 ml/hr , pre or post filter (up to 3
lit/hr).
Anticoagulation
NO dialysate
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Effective for removal of small to medium sized molecules.
Solute removal occurs primarily due to diffusion.
No replacement fluid is used.
Dialysate is run on the opposite side of the filter.
Fluid in the effluent bag is equal to the amount of fluid
removed from the patient plus the dialysate.
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Blood flow:80 – 200 ml/min
Duration
Ultrafiltration: 20 -100 ml/hr (or total volume)
Anticoagulation
Dialysate: 600 – 1800 ml/hr (up to 3 lit/hr).
NO replacement fluid
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The most flexible of all the therapies, and combines the
benefits of diffusion and convection for solute removal.
The use of replacement fluid allows adequate solute
removal even with zero or positive net fluid balance for
the patient.
Amount of fluid in the effluent bag equals the fluid
removed from the patient plus the dialysate and the
replacement fluid.
Dialysate on the opposite side of the filter and replacement
fluid either before or after the filter.
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Blood flow: 80 – 200 ml/min
Duration
Ultrafiltration: 20-100 ml/hr (or total volume)
Anticoagulation
Dialysate: 600 – 1800 ml/hr (up to 3 lit/hr).
Replacement fluid: 1000-2000 ml/hr, pre or post
filter (up to 3 lit/hr).
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Low-dose pre-filter unfractionated Heparin: any dose less
than 5 units/kg/hour.
Medium-dose pre-filter unfractionated Heparin: a dose
between 8-10 units/kg/hour.
Systemic unfractionated Heparin is administered
intravenously and titrated to achieve an activated partial
thromboplastin time (aPTT) ordered by the physician, for
patients who have another indication for heparinization,
such as .DVT
Regional unfractionated Heparin: a pre-filter dose of 1500
units/hour of Heparin, with administration of Protamine
post-filter at a dose of 10-12 mg/hour.
Low-molecular-weight Heparins
Prostacyclin: rarely used (expensive, hypotension)
Citrate: infused pre-filter, Ca must be replaced.
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Platelet count < 50,000/mm3
INR > 2.0
aPTT > 60 seconds
Actively bleeding or with an active bleeding episode
in the last 24 hours
Severe hepatic dysfunction or recent liver
transplantation
Within 24 hours post cardiopulmonary bypass or
extra-corporeal membrane oxygenation (ECMO)
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Bleeding
Hypothermia
Electrolyte imbalance
Acid-base imbalance
Infection
Dosing of medications
WHAT
HOW
Is CRRT
To use CRRT
HOW
To use CRRT
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When to start CRRT.
IHD Vs CRRT.
Dose of CRRT.
Anticoagulation and CRRT.
Nutrition and CRRT.
Drug doses in CRRT.
Ethical issues of CRRT.
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Further studies focused mostly on the timing of
initiation of CRRT
Gettings et al published a retrospective analysis of
100 consecutive patients with post traumatic AKI in
1999
Early vs late initiation based on BUN < or > 60
mg/dL at initiation of therapy
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Early group
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Late group
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CRRT initiated on hospital day 10+15
Mean BUN of 43+13
CRRT initiated on HD 19+27 mg/dl
BUN of 94+28 mg/dl
Survival – 39% in early Vs 20% in late group
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Critical points:
Non-randomized, retrospective
 More pts with multi-system organ failure or sepsis in late
group
 More pts oliguric on first day of CRRT in early than late
group, leading to suggestion that there was a confounding
effect (?physician bias)
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Bouman et al (2002)randomized 106 critically ill patients
with AKI to three groups:
 Early high-volume CVVHDF (35 pts)
 Early low-volume CVVHDF (35 pts)
 Late low-volume CVVHDF (36 pts)
Two early groups – txt started within 12 hrs of meeting
inclusion criteria:
 Oliguria x 6 hrs despite hemodynamic optimization
 Measured cr clearance <20 ml/min on a 3-hr timed
collection
Late groups:
 BUN>112
 K>6.5
 Pulmonary edema present
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No significant differences in survival were observed
Critical point is that 28-day mortality was only 27%,
much lower than in previously reported studies of
critically ill patients with AKI
Small sample size lead to low statistical power
Interestingly, 6/36 pts in late group never got RRT
(2 pts died and 4 pts recovered renal function)
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Patients were divided into early or late dialysis groups based on an
arbitrary blood urea nitrogen cut-off level of 80 mg/dL before renal
replacement therapy.
Earlier initiation of renal replacement therapy, based on the
predialysis blood urea nitrogen level, with continuous venousvenous hemofiltration might provide a better ICU survival rate.
Journal of the American College of Surgeons
Volume 205, Issue 2, August 2007, Pages 266-276
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multi-center, randomized controlled trial with 1,508
critically ill AKI patients in Australia and New Zealand.
2 groups: higher-intensity group (CRRT dose of 40
mL/kg/hr) or a lower-intensity group (CRRT dose of 25
mL/kg/hr).
Early initiation may have contributed to excellent
outcomes (mean, 50 hours).
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Inadequate data available to answer this question
Observational data suggests better outcomes are
associated with early RRT initiation
? If “less sick” patients are included in these early
groups
Also, many patients with AKI are not treated with
RRT
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Objective: The impact of CRRT and IHD on renal
recovery.
Design: retrospective cohort study between the
years 1995 and 2004. Follow-up ranged between 3
months and 10 years.
Patients: 2202
90 days survival: 85.7% with CRRT, 14.3% with
IHD
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Conclusions: Although further study is needed, this
study suggests that renal recovery may be better
after CRRT than IHD for ARF.
Mortality was not affected significantly by RRT
mode.
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Objectives: To estimate the impact of hemodialysis
modality on patient outcome.
Design: Prospective multicenter observational study
conducted from March 1996 to May 1997.
28 ICUs, 587 patients, France.
Conclusions: Renal replacement therapy mode was
not found to have any prognostic value.
Randomized controlled trials should be undertaken
to assess this important question.
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The concept of RRT dose is part of the required
knowledge for a safe and effective delivery of
therapy.
As is the case for antibiotics, vasopressors, antiinflammatory drugs, mechanical ventilation, etc.
In chronic kidney disease, urea often has been used
as a marker molecule.
The amount (dose) of delivered RRT can be
described by various terms: efficiency, intensity,
frequency, and clinical efficacy.
The volume of blood cleared of a given solute over
a given time.
(mL/min, mL/hr, L/hr, L/24 hrs, etc.)
 During RRT, K depends on solute molecular size
and diffusivity, transport modality (convection or
diffusion), and circuit operational characteristics
such as blood flow rate, ultrafiltration rate, dialysate
flow rate, and membrane and hemodialyzer type and
size.
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Defined as: The product of K X time.
(Kt: mL/min X 24 hrs, L/hr X 4 hrs, etc.)
Kt is more useful than K in comparing various
RRTs.
Nevertheless, equal Kt products may lead to
different results if K is large and t is small or if K is
small and t is large.
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The effective outcome resulting from the
administration of a given treatment dose to a given
patient.
V: is the volume of distribution of the marker
molecule in the body.
Kt/V is a dimensionless number(e.g., 3 L/hr X 24
hrs/45 L = 72 L/45 L = 1.6)
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The marker solute cannot and does not represent all
of the solutes that accumulate in renal failure.
Its kinetics and volume of distribution are also
different from other solutes.
Finally, its removal during RRT is not representative
of the removal of other solutes.
This is true for both end-stage renal failure and
acute renal failure.
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Brause et al. (2008), using CVVH, found that
higher Kt/V values (0.8 versus 0.53) were correlated
with improved uremic control and acid-base
balance.
Paganini EP (2001):A mean Kt/V >1.0 was
associated with increased survival.
Ronco C (2000): A randomized, controlled trial of
CRRT dose, CVVH at 35 or 45ml/kg per h was
associated with improved survival when compared
with 20 ml/kg per h in 425 critically ill patients with
ARF .
Effects of different doses in CVVH on outcome of ARF - Ronco & Bellomo
study. Lancet . july 00
100
p < 0.001
Survival (%)
90
80
70
p < 0.001
p n.s.
60
50
40
30
20
41 %
57 %
58 %
10
0
306100135
Group 1(n=146)
Group 2 (n=139)
Group 3 (n=140)
(Uf = 20 ml/kg/hr)
(Uf = 35 ml/kg/hr)
(Uf = 45 ml/kg/hr)
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Bouman C et al (2002):3 groups
Early high-volume hemofiltration (72 to 96 L/24 h).
Early low-volume hemofiltration (24 to 36 L/24 h).
Late low-volumehemofiltration (24 to 36 L/24 h).
No difference in terms of renal recovery or
28-d mortality regarding the dose.
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Prevent clotting of the circuit.
Preserve filter performance.
Optimize circuit servival.
Prevent loss of blood due to circuit clotting.
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Should prevent filter clotting without inducing
hemorrhage.
Should have a short half-life, and action limited to
extracorporeal circuit.
Should be easily monitored.
Should have No systemic side effects.
Should have an antidote.
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Low-dose pre-filter unfractionated Heparin: any dose less
than 5 units/kg/hour.
Medium-dose pre-filter unfractionated Heparin: a dose
between 8-10 units/kg/hour.
Systemic unfractionated Heparin is administered
intravenously and titrated to achieve an activated partial
thromboplastin time (aPTT) ordered by the physician, for
patients who have another indication for heparinization,
such as .DVT
Regional unfractionated Heparin: a pre-filter dose of 1500
units/hour of Heparin, with administration of Protamine
post-filter at a dose of 10-12 mg/hour.
Low-molecular-weight Heparins
Prostacyclin: rarely used (expensive, hypotension)
Citrate: infused pre-filter, Ca must be replaced.
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Kozek-Langenecker et al (2002).
Fiaccadori E et al (2002).
Nakae H et al (2003).
Attractive strategy that has its
drawbacks
(HIT, bleeding)
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5000 – 20000 U of UFH added to the priming
solution.
Continuous infusion of 3-5 u/kg/hr.
50 – 100 % prolongation of aPTT.
Incidence of bleeding varied between 0 – 50 %
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Pre-filter citrate inhibits coagulation by chelating
Ca+
As a result iCa decreases.
An iCa concentration below 0.35 mmol/L is
required to inhibit coagulation.
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RCT, 144 patients.
Safety and efficacy of regional anticoagulation with
citrate in critically ill patients with AKF, without an
increased risk of bleeding.
Nadroparin group Vs Citrate group.
Hb concentration lower in N group (p=0.002)
ICU mortality lower in C group than N group (25%
Vs 30% , p< 0.01)
Hospital mortality lower in C group than N group
(40% Vs 48%, p = 0.065)
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Prospective dose finding study.
30 patients with acute or history of HIT.
ARF in need of CRRT.
Safety determined by:
- steady state of BUN 32.16 ±18.02 mg/dl
- mean filter patency at 24 hrs: 98%
- Bleeding episodes.
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Argatroban loading dose of 100 µ/kg
Followed by maintenance infusion rate ( µ/kg/min)
Maintenance infusion calculated by:
2.15 – 0.06 X APACHE II score
Conclusion: In critically ill patients with HIT and
necessity for CRRT , APACHE II can help to predict
the required argatroban maintenance dose for
anticoagulation.
This predictor identifies decreased argatroban
dosing requirements.
Resulting in effective and safe CRRT.
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Anticoagulation during CRRT should be
individualized.
The first goal should be the safety of the patient.
Attention should be paid to non-pharmacological
means of prolonging filter life (blood flow, wide
pore cath, pre-filter replacement fluid).
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ARF causes anorexia, nausea, vomiting, bleeding
ARF causes rapid nitrogen loss and lean body mass
loss (hypercatabolism)
ARF causes ↑ gluconeogenesis with insulin
resistance
Dialysis causes loss of amino acids and protein
Uremia toxins cause impaired glucose utilization
and protein synthesis
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Calories: 25-45 kcals/kg dry weight or REE
Protein: about 10-16 g amino acids lost per day with
CRRT
ARF w/o HD (expected to resolve within a few days): .6-1
g pro/kg
 Acute HD: 1.2-1.4 g/kg; acute PD: 1.2-1.5 g/kg; CRRT:
1.5-2.5 g/kg
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CHO: ~60% total calories; limit to 5 mg/kg/min;
peripheral insulin resistance may limit CHO
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In CWHD(F) watch for CHO in dialysate or replacement
fluids
Fat: 20-35% of total calories; lipid clearance may be
impaired
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Vitamin A: elevated vitamin A levels are known to
occur with RF
Vitamin B – prevent B6 deficiency by giving 10 mg
pyridoxine hydrochloride/day
Folate and B6: supplement when homocysteine
levels are high
Vitamin C: <200 mg/day to prevent ↑ oxalate
Activated vitamin D
Vitamin K: give Vitamin K especially to pts on
antibiotics that suppress gut production of K
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↑ potassium, magnesium, and phos occur often due
to ↓ renal clearance and ↑ protein catabolism
↓ potassium, mg and phos can occur with refeeding
CRRT pts can have ↓ K+, phos
Mg deficiency can cause K+ deficiency resistant to
supplementation
Vitamin C, copper, chromium lost with CVVH
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Depends on residual renal function, fluid and
sodium status, other losses
Usually 500 mL/day + urine output
Fluid replacement needs can be ↑ with CRRT
Extracorporeal removal
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only the drug in the central compartment（plasma）
is available for extracorporeal removal
drugs with a large Vd have less access to the
hemofilter or dialyzer
Extracorporeal treatmentdeeper compartments
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the rate of extracorporeal removal
 the rate of transfer between the peripheral and central
compartment.
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Molecular weight.
Volume of distribution.
Plasma protein binding.
Drug charge (Gibbs-Donnan effect).
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Membrane.
Diffusion.
Convection.
Adsorption to membrane.
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Design: A questionnaire.
Setting: The First International Course on Critical
Care Nephrology.
Participants: The participants in the course (around
500).
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Most participants think that establishing ethical
criteria for managing CRRT is a medical task.
Many responders would start futile CRRT or
maintain it if requested by the family.
Only 55% believe that informed consent is
necessary for initiating CRRT.
One out of four would start or maintain unwanted
life-saving CRRT.
Most think that every vital support should be
withdrawn when futile