1. Continous Renal
Replacement Therapy
Basic Principles and Definitions
By
Dr. Marwa Ahmad
Assistant lecturer
Anesthesia and Intensive care departement
Sohag university

2. What is the 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.

3. The concept behind continuous
renal replacement techniques is
to dialyse patients in a more
physiologic way, slowly, over 24
. hours, just like the kidney

4. Intensive care patients are particularly
suited to these techniques as they are,
by definition, bed bound, and, when
acutely sick, intolerant of the fluid
swings associated with IHD.

5. CRRT refers to any continuous mode of
. extracorporeal solute or fluid removal
A variety of renal replacement therapies are
encompassed within the term CRRT. Common
to all forms of CRRT is an extracorporeal circuit
connected to the patient via an arterial or venous
.access catheter, or both

6. All CRRT circuits include a hemofilter
with a semipermeable membrane.
By connecting the hemofilter to the
patient’s circulation, fluid can be
removed from the patient on the basis
of the hydrostatic pressure gradient
across the filter.

7. The rate of fluid removal is affected by
either the patient’s arterial blood
pressure (when an arterial cannula is
used) or by the pressure generated with
an extracorporeal pump (for venous
cannulation techniques).
The ultrafiltrate is composed of water as
well as compounds with a molecular
weight of up to approximately 20,000Da

8. Traditional intermittent hemodialysis
often causes hemodynamic instability
.in the critically ill
Continuous renal replacement therapy
(CRRT) was developed in the 1980s in
an effort to provide artificial kidney
support to patients who could not
.tolerate traditional hemodialysis

9. The earliest forms of CRRT used arterial
and venous access and depended on
the patient’s mean arterial pressure to
. push blood through the filter
This technique was rarely successful for
patients in shock – those who needed
. the continuous therapy the most

10. In response to this shortcoming, the
current techniques of veno-venous
. CRRT were developed
Most CRRT delivered today uses veno-
venous access and an external blood
pump to maintain adequate flow
.through the filter

11. Difference between CRRT and
conventional Dialysis
two major dialysis techniques:
conventional intermittent
haemodialysis (IHD) and continuous
(.renal replacement therapy (CRRT
One difference between these two
:options is fairly evident
the time during which they are applied.

12. CRRT is, in theory, applied
continuously, whereas IHD, just like
chronic haemodialysis, is applied for
only a few hours during the day.

13. Because of the short treatment time,
IHD needs to deliver highly efficient
.therapy for toxin and fluid removal
In contrast, CRRT modalities are mostly
rather low-efficiency techniques, and
therapy needs to be continuous in
. order to be adequate

14. Differences
i) IHD is mostly performed as a mainly)
diffusive therapy across a low-flux
dialysis membrane, with a high
dialysate flow, which necessitates on-
line dialysate production, a water-
treatment module and a dialysis
. monitor

15. (ii) In contrast, CRRT is performed
mostly as convective therapy across a
high-flux membrane, and using
industry-prepared substitution fluid in
bags.

16. (iii) It is clear that the application of IHD
needs the nursing and technical
expertise of a dialysis team, whereas
CRRT is technically less demanding.

17. Based on these differences, it must
unfortunately be admitted that the
choice between CRRT and IHD is often
reduced to a question of whether the
intensivist or nephrologist is
responsible for the treatment of ARF in
the ICU.

18. :Conventional renal dialysis
With renal failure of any cause, there
are many physiologic derangements.
Homeostasis of water and minerals
(sodium, potassium, chloride,
calcium, phosphorus, magnesium,
sulfate), and excretion of the daily
metabolic load of fixed hydrogen ions
.is no longer possible

19. Toxic end-products of nitrogen
metabolism (urea, creatinine, uric
acid, among others) accumulate in
.blood and tissue
Finally, the kidneys are no longer able
to function as endocrine organs in the
production of erythropoietin and 1,25
(.dihydroxycholecalciferol (calcitriol

20. Dialysis procedures remove nitrogenous
end-products of catabolism and begin
the correction of the salt, water, and
acid-base derangements associated
.with renal failure

21. Renal function should not be estimated
from measurements of blood urea or
creatinine alone. Cockcroft and Gault
equation or reciprocal creatinine plots
should not be used when the GFR is
<30 mL/min or to determine the need
for dialysis.

22. Indications of dialysis in acute renal
(failure (ARF
•Severe fluid overload
•Refractory hypertension
•Uncontrollable hyperkalemia
•Nausea, vomiting, poor appetite, gastritis with
hemorrhage
•Lethargy, malaise, somnolence, stupor, coma,
delirium, asterixis, tremor, seizures,
•Pericarditis (risk of hemorrhage or tamponade)
•bleeding diathesis (epistaxis, gastrointestinal (GI)
bleeding and etc.
•Severe metabolic acidosis
•Blood urea nitrogen (BUN) > 70 – 100 mg/dl

23. Indications of dialysis in chronic
(renal failure (CRF
• Pericarditis.
• Fluid overload or pulmonary edema refractory to
diuretics.
• Accelerated hypertension poorly responsive to
antihypertensives.
• Progressive uremic encephalopathy or neuropathy
such as confusion, asterixis, myoclonus, wrist or
foot drop, seizures.
• Bleeding diathesis attributable to uremia.

24. Principle of dialysis
Dialysis works on the principles of the
diffusion of solutes and ultrafiltration of fluid
across a semi-permeable membrane.
Diffusion describes a property of substances
in water. Substances in water tend to move
from an area of high concentration to an area
of low concentration.

25. Blood flows by one side of a semi-permeable
membrane, and a dialysate, or special
dialysis fluid, flows by the opposite side.
A semipermeable membrane is a thin layer of
material that contains holes of various sizes,
or pores.

26. Smaller solutes and fluid pass through the
membrane, but the membrane blocks the
passage of larger substances (for example, red
blood cells, large proteins).
This replicates the filtering process that takes
place in the kidneys, when the blood enters
the kidneys and the larger substances are
separated from the smaller ones in the
glomerulus.

27. The need to CRRT
When comparing continuous renal replacement
therapy (CRRT) with intermittent therapy, it is wise to
remember that the very reason for the development
and introduction of CRRT into clinical practice in the
late 1970s and early 1980s was to compensate for
the clear inadequacies of conventional intermittent
hemodialysis (IHD) in the treatment of critically ill
patients with multi-organ failure.
If there had not been serious problems with
conventional IHD, CRRT would not be the subject for
discussion.

28. Critically ill patients requiring renal
replacement therapies cannot tolerate rapid
fluid and electrolyte shifts without significant
.hemodynamic compromise
Even if these hypotensive episodes are brief,
they may result in further damage to the
kidney. Multiple hypotensive episodes have
been shown to slow recovery from acute
.renal failure in the critically ill

29. The critically ill patient is also susceptible to
protein calorie malnutrition due to the
Marked catabolism that accompanies critical
illness.
In order to provide adequate protein to these
patients, large amounts of fluids and protein must be
administered, either enterally or parenterally.
Intermittent hemodialysis (IHD) requires that
patients’ protein and fluid intake be limited between
treatments to prevent toxic levels of nitrogen and
fluid overload.

30. CRRT addresses the needs of the critically ill
patient with renal dysfunction and/or fluid
volume excess by providing slow, continuous
removal of toxins and fluids.
By removing fluids continuously over a 24
Hour period, CRRT mimics the native kidney.

31. Hemodynamic stability is improved, and
multiple hypotensive episodes are
significantly reduced.
Because there is no buildup of toxins and
fluids,patients receiving CRRT can receive as
much protein and fluid as needed to achieve
optimal nutrition.

32. Indications of CRRT

33. 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.
This pattern more closely mimics the native
kidney and prevents abrupt shifts in fluid,
electrolyte and acid-base balance.

34. Indications for renal replacement therapy
(RRT) fall into two broad categories, so-called
“renal” (i.e., to specifically address the
consequences of renal failure) and “nonrenal”
(without necessitating renal failure).
Although the distinction is not always
precise,
it is a reasonably easy way to categorize
indications for RRT.

35. Renal indications
• Volume overload (e.g., pulmonary
edema)
• Azotemia with uremic symptoms
• Hyperkalemia (>6.0 mmol/L)
• Metabolic acidosis (pH < 7.2) due to
renal failure

36. “Nonrenal” indications
So-called nonrenal indications for RRT
are to remove various dialyzable
substances from the blood.
These substances include drugs,
poisons, contrast agents, and cytokines.

37. Drug and toxin removal
Continuous renal replacement therapy
(CRRT) may be effective in removing
substances with higher degrees of protein
binding and is sometimes used to remove
substances with very long plasma half-lives.
Techniques such as sorbent hemoperfusion
may also be used for this indication.

38. In general, the size of the molecule and
the degree of protein binding
determines the degree to which the
substance can be removed (smaller,
nonprotein bound substances are
easiest to remove).

39. The role of CRRT in the management of acute
poisonings is not well established.
There is relatively lower drug clearance per
unit of time compared to intermittent
hemodialysis (IHD) but CRRT has a distinct
advantage in hemodynamically unstable
patients who are unable to tolerate the rapid
solute and fluid losses associated with IHD or
even other techniques such as
hemoperfusion.

40. CRRT may also be effective for the slow,
continuous removal of substances with large
volumes of distribution, a high degree of
tissue binding, or for substances that are
prone to “rebound phenomenon” (e.g.,
lithium, procainamide, and methotrexate).
In such cases, CRRT may even be
used as adjuvant therapy with IHD or
hemoperfusion.

41. Contrast agents
all radio-contrast agents are nephrotoxic and
CRRT is being advocated by some experts to
help prevent so-called contrast nephropathy.
Standard IHD has been shown to remove
radio-contrast agents but does not appear to
prevent contrast nephropathy.
Despite less efficiency in removing contrast,
CRRT has been shown to result in less
contrast nephropathy, particularly when it
has begun prior to or in conjunction with
contrast administration.

42. Cytokines
Many endogenous mediators of sepsis can be
removed using continuous venovenous
hemofiltration (CVVH) or continuous veno-
venous hemodiafiltration(CVVHDF) (dialysis is
not able to remove these mediators).
This observation has prompted many
investigators to attempt to use CVVH as an
adjunctive therapy in sepsis.

43. While it remains controversial as to
whether CVVH offers additional benefit
in patients with renal failure and sepsis,
available evidence does not support a
role of CVVH for the removal of
cytokines in patients without renal
failure.

44. Contra indications of CRRT
•Advance directives indicating the
patient does not desire dialysis, or that
the patient does not desire life-
sustaining therapy.
• Patient or family refusal of therapy.
• Inability to establish vascular access.

45. Principles of renal replacement
therapy
Renal replacement always uses a
semipermeable membrane to achieve blood
purification.
It can be intermittent or continuous, and can involve
any of 4 major transport mechanisms: diffusion,
convection, adsorption and ultrafiltration.
The focus of this packet is continuous renal
replacement therapies.

46. Semipermeable Membranes
Semipermeable membranes are the
basis of all blood purification therapies.
They allow water and some solutes to
pass through the membrane, while
cellular components and other solutes
remain behind.

47. The water and solutes that pass
through the membrane are called
ultrafiltrate.
The membrane and its housing are
referred to as the filter.

48. Ultrafiltration
Ultrafiltration refers to the passage of water
through a membrane under a pressure
gradient.
Pressures that drive ultrafiltration can be
positive, that is the pressure pushes fluid
through the filter.
They can also be negative, there may be
suction applied that pulls the fluid to the
other side of the filter.

49. The rate of ultrafiltration will depend upon
the pressures applied to the filter and on the
rate at which the blood passes through the
filter.
Higher pressures and faster flows increase
the rate of ultrafiltration.
Lower pressures and slower flows decrease
the rate of ultrafiltration.

50. Convection
Convection is the movement of solutes
through a membrane by the force of water.
Convection is sometimes called “solvent drag”.
Convection is able to move very large
molecules if the flow of water through
the membrane is fast enough.

51. In CRRT this property is maximized by using
replacement fluids.
Replacement fluids are crystalloid fluids administered
at a fast rate just before or just after the blood
enters the filter.
The increased fluid flow rate across the filter allows
more molecules to be carried through to the other
side.

52. 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.

53. Adsorption
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.

54. Diffusion
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.

55. 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. To understand diffusion,
think of adding drops of food coloring to a bathtub.
Initially the coloring appears as a dense cloud, but over
time the coloring spreads (diffuses) evenly throughout the
water.

57. Vascular Access and the Extracorporeal
Circuit
There are two options for vascular access for
CRRT, venovenous and arteriovenous.
Venovenous access is by far the most commonly
used in the modern ICU.

58. Fluids Used in CRRT
Dialysate
Dialysate is any fluid used on the bopposite side of
the filter from the blood during blood
purification.
Dialysate is a crystalloid solution containing various amounts of
electrolytes, glucose, buffers and other solutes. The most common
concentrations of these solutes are equal to normal plasma levels.
The concentration of solutes will be ordered by the physician based
on the needs of the patient.
Typical dialysate flow rates are between 600 – 1800 mL/hour.

59. Replacement Fluids
As stated earlier, replacement fluids are used to increase the
amount of convective solute removal in CRRT. It is very
important to understand that despite their name,
Replacement fluids do not replace anything.
Many professionals new to CRRT mistakenly believe that
If replacement fluids are added to the therapy, fluid
removal rates are decreased or eliminated.

60. This is not the case. Fluid removal rates are
calculated independently of replacement fluid rates.
The most common replacement fluid is 0.9%Normal
Saline.
Other crystalloid solutions may also be used as
replacement fluid. Sometimes an additive will be added to
the replacement fluid bag to aid in correction of electrolyte
or acid-base balance.

61. Anticoagulation & CRRT
Anticoagulation is needed in CRRT because the
clotting cascades are activated when the blood
touches the non-endothelial surfaces of the tubing
and filter. CRRT can be run without
anticoagulation, but filters last much longer if
some form of anticoagulation is used.

62. Types of CRRT Therapy
CRRT encompasses several therapeutic modalities:
• Slow Continuous Ultrafiltration (SCUF)
• Continuous VenoVenous Hemofiltration
(CVVH)
• Continuous VenoVenous HemoDialysis
(CVVHD)
• Continuous VenoVenous HemoDiaFiltration
(CVVHDF)

63. (Slow Continuous Ultrafiltration (SCUF
To perform SCUF, the patient is placed on the
CRRT machine and the blood is run through the
filter. No dialysate or replacement fluid is used. The
primary indication for SCUF is fluid overload
without uremia or significant electrolyte
imbalance.

64. SCUF therapy primarily removes water from the
bloodstream. The main mechanism of water transport is
ultrafiltration. Other solutes are carried off in small
amounts, but usually not enough to be clinically significant.
When performing SCUF, the amount of fluid in the effluent bag is
the same as the amount removed from the patient.
Fluid can be removed at a rate of up to 2 L/hour using SCUF, but
this defeats the purpose of continuous therapy. Fluid removal rates
are typically closer to 100 mL/hour.

65. Continuous Veno-venous
(Hemofiltration (CVVH
To perform CVVH, the patient is placed on the
CRRT machine and blood is run through the
filter with a replacement fluid added either before or
after the filter. No dialysate is used.
CVVH can be an extremely effective method of solute
removal and is indicated for uremia or severe pH or
electrolyte imbalance with or without fluid overload.
Because CVVH removes solutes via convection, it is
particularly good at removal of large molecules.

66. One major advantage of CVVH is that solutes can be
removed in large quantities while easily maintaining a net
zero or even a positive fluid balance in the patient.
This flexibility makes CVVH an ideal therapy for patients
who have severe renal impairment combined with a need
to maintain or increase fluid volume status.
When performing CVVH, 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.

67. Continuous Veno-venous
(Hemodialysis (CVVHD
To perform CVVHD, the patient is placed on the
CRRT machine and dialysate is run on the
opposite side of the filter, no replacement fluid is
used.
CVVHD is very similar to traditional hemodialysis, and is
effective for removal of small to medium sized molecules.
Solute removal occurs primarily due to diffusion, and
dialysate can be tailored to promote diffusion of specific
molecules.

68. While CVVHD can be configured to allow a
positive or zero fluid balance, it is more difficult
than with CVVH because the rate of solute
removal is dependent upon the rate of fluid
removal from the patient.
When performing CVVHD the amount of fluid in
the effluent bag is equal to the amount of fluid
removed from the patient plus the dialysate.

70. Continuous Veno-venous
(Hemodiafiltration (CVVHDF
To perform CVVHDF the patient is placed on the
CRRT machine with dialysate running on the
opposite side of the filter and replacement fluid either
before or after the filter.
CVVHDF is the most flexible of all the therapies,
and combines the benefits of diffusion and
convection for solute removal.

71. The use of replacement fluid allows adequate
solute removal even with zero or positive net fluid
balance for the patient. The replacement fluid
rates and dialysate rates are similar to those
described for CVVHD and CVVH.
In CVVHDF the amount of fluid in the effluent bag
equals the fluid removed from the patient plus the
dialysate and the replacement fluid.

72. Prescription of CRRT
A typical prescription for a 75kg patient requiring
CRRT for an AKI would be as follows:
Anticoagulation:
Unfractionated Heparin: 5,000 IU bolus followed by a
pre-filter infusion at 500 IU.hr.-1
Aim to anticoagulate filter but ensure APTTR<2

73. Fluid balance over 24 hours:
Aim for an even balance if the patient is euvolaemic
Aim for the appropriate negative balance if the patient is fluid
overloaded (<1500ml/24hrs)
Type of Replacement fluid/Dialysate:
Use solutions without potassium if serum potassium is high but
switch to potassium containing solutions as serum potassium
normalises
Use a bicarbonate-based buffer rather than a lactate-based
buffer if there are concerns about lactate metabolism or if
serum lactate>8mmol.l.-1 [Note- An intravenous bicarbonate
infusion may be required if a lactate-based buffer is used]

74. Exchange rate/treatment dose:
1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)
The treatment dose is usually prescribed as an hourly “exchange
rate” which is the desired hourly flow rate adjusted for the
patient`s weight
In the case of CVVH, the exchange rate simply represents the
ultrafiltration rate whereas in CVVHDF it represents a
combination of the ultrafiltration rate and the dialysate flow
rate
In CVVHDF, the ratio of ultrafiltration to dialysate flow is often set at
1:1 but it can be altered to put the emphasis on either the dialysis or
filtration component

76. Complications of CRRT
Bleeding
Hypothermia
Electrolyte Imbalances
Acid-Base Imbalances
Infection
Appropriate Dosing of Medications