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The basic principles of continuous renal replacement therapy

Article  in  Journal of Renal Nursing · March 2013

DOI: 10.12968/jorn.2013.5.2.85

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 practice
The basic principles of continuous
renal replacement therapy
Continuous renal replacement therapy (CRRT) is the recommended treatment for patients with acute
renal injury being treated in the intensive care unit. This article explains the principles behind it, the
advantages over intermittent haemodialysis and the potential problems with the technique.
continuous
n  renal replacement therapy n acute renal injury n intermittent haemodialysis
A
cute kidney injury (AKI) is the sudden
decrease in kidney function over a period of
hours or days, resulting in accumulation of
creatinine, urea and other waste products.
It may be associated with retention of sodium and water
and the development of metabolic disturbances, such as
metabolic acidosis and hyperkalaemia. AKI accounts for
about 1% of hospital admissions and develops in 5–7%
of hospitalized patients [AQ1. Is this Uchino reference
too? and wording has been changed- happy?]. In
the intensive care unit (ICU) AKI develops in 5–25%
of patients; with approximately 6% requiring renal
replacement therapy (RRT) during their ICU stay
(Uchino et al, 2005). However, the mortality rate among
ICU patients with AKI and multi-organ failure is high,
reported to be more than 50%, and if RRT is required,
mortality may be as high as 80% (Brivet et al, 1996).
Acute tubular necrosis is the most common cause
of hospital-acquired AKI and usually results from
ischaemic or nephrotoxic injury to the tubules. No
specific pharmacologic therapy is effective and the care
of such patients is limited to supportive treatment,
including RRT [AQ2. Is treatment chiefly limited to
supportive measures in all AKI patients, or just those
whose condition stems from acute tubular necrosis?].
Renal replacement therapy of critically ill patients with AKI who could not
RRT involves water and solutes passing through a semi-
permeable membrane and the waste products being
discarded. The processes involved are ultrafiltration,
convection, and diffusion. Ultrafiltration is the
process by which plasma water is forced across a
semi-permeable membrane by hydrostatic pressure.
Convection occurs when the transmembrane pressure
gradient drives water across a semi-permeable
membrane, as in ultrafiltration, but drags solutes with
Graham Cope
n Honorary Senior Research Fellow University of Birmingham and Freelance
Medical Writer n graham@copecommunications.com
38
JRN_5_2_CRRT_edit.indd 38
n intensive care
the plasma. Diffusion occurs when solute removal
across the membrane is driven by a gradient in
the concentration of the solute between the blood
on one side of the membrane and an electrolyte
solution (the dialysate) on the other side (Figure
1). The concentration gradient is maximized and
maintained throughout the length of the membrane
by running the dialysate in the opposite direction, or
countercurrent, to the blood flow.
Traditionally, nephrologists have managed AKI
with intermittent haemodialysis (IH), in which
solute clearance occurs mainly by diffusion, whereas
volume is removed by ultrafiltration. The advantages
of IH include rapid removal of solute and volume,
but the main disadvantage is the risk of systemic
hypotension, which occurs in approximately 20–30%
of haemodialysis treatments [AQ3. Is this Selby
and McIntyre ref?]. Approximately 10% of patients
with AKI cannot be treated with IH because of
haemodynamic instability (Selby and McIntyre, 2006).
Continuous renal
replacement therapy
Continuous renal replacement therapy (CRRT)
includes a spectrum of dialysis methods. It was
developed in the 1980s specifically for the treatment
undergo traditional IH because of haemodynamic
instability, or in whom IH could not control volume
or metabolic derangements (Cerdá and Ronco, 2009).
The slower solute clearance and removal of fluid per
unit of time with CRRT is thought to allow for better
haemodynamic tolerance than with IH.
In current practice, the blood circuit for CRRT is
usually a venovenous circuit. Venous blood is removed
from the circulation through one lumen of a double-
lumen, large-bore catheter. It then passes through a
peristaltic blood pump, which generates the perfusion
pressure that drives the ultrafiltration of plasma water
across a biosynthetic haemofiltration membrane, thus
removing volume. Solute is removed by:
nnConvection: continuous venovenous
journal of renal nursing vol 5 no 3 March 2013
19/02/2013 11:20

haemofiltration
n Diffusion: continuous venovenous
haemodialysis
n Or both convection and diffusion: continuous
venovenous haemodiafiltration (Credo and
Ronco, 2009) (Table 1).
In each case, the blood is then returned to the
venous circulation through the second lumen of the
catheter. In the two methods that use convection
for removal of solute (continuous venovenous
haemofiltration and continuous venovenous
haemodiafiltration), a high ultrafiltration rate is
required to achieve convective clearance; as a result,
replacement fluid must be added before or after the
haemofilter in the extracorporeal circuit to restore fluid
volume and electrolytes (Tolwan, 2012).
Advantages of continuous renal
replacement therapy
No randomized, controlled trials have shown that CRRT
is superior to IH with respect to survival. The Cochrane
Collaboration performed a meta-analysis of 15
randomized, controlled trials involving 1550 critically
ill patients with AKI and concluded that CRRT did not
differ significantly from IH with respect to hospital
mortality, ICU mortality or the number of surviving
patients who did not require RRT (Rabindranath et
al, 2007). However, CRRT has advantages that may
influence its use despite the lack of a demonstrated
survival benefit. In the Cochrane analysis, patients who
received CRRT had significantly higher mean arterial
pressures than patients who received intermittent
renal replacement therapy (Rabindranath et al, 2007).
Removal of fluid with short sessions of IH can induce
intradialytic hypotension, potentially increasing the
risk of recurrent kidney injury. Perhaps as a result, IH
has been associated with positive fluid balance, whereas
CRRT may permit better management of fluid volume,
allowing for adequate nutrition without compromising
fluid balance (Bouchard et al, 2009).
At present, there is no consensus regarding when
to prescribe RRT; this lack of agreement has resulted
in a wide variation in clinical practice. However,
there is little debate that hyperkalaemia, severe
metabolic acidosis, volume overload, overt uraemic
manifestations, and drug intoxications are clear
indications for the initiation of therapy (Table 2).
Early initiation
Early initiation of RRT in patients with AKI is
associated with improved survival [AQ 4. Do you
have a reference for this statement?]. Clinicians
often initiate RRT in patients before the development
of overt complications of AKI, taking into account
the overall clinical state of the patient and various
factors, including the patient’s age, the severity of
vol 5 no 3 March 2013 journal of renal nursing
JRN_5_2_CRRT_edit.indd 39
practice
Figure 1.The types of fluid and solute transfer through a semi-
permeable membrane in continuous renal replacement therapy
Ultrafiltration is the process by which plasma water is forced across a semi-permeable
membrane by hydrostatic pressure. The driving force is a pressure gradient across the
membrane which can be created in different ways:
a) positive pressure b) negative pressure c) osmotic pressure
a) Positive pressure in the left compartment will ‘push’ fluid through the membrane
b) Negative pressure on the left compartment will ‘suck’ fluid through the membrane
c) Non-permeable solutes create an osmotic pressure. The water will move from the area
of high water concentration to the area of the lower water concentration.
Convection occurs when the transmembrane pressure gradient drives water across a
semi-permeable membrane (as in ultrafiltration) but drags solutes with the plasma:
Diffusion occurs when the solute removal across the membrane is driven by a gradient in
the concentration of the solute between the blood on one side of the membrane and an
electrolyte solution (the dialysate) on the other side:
Source: American Association of Critical Care Nurses (2008)
illness, other organ dysfunction, and the degree of
renal dysfunction. However, most opinion leaders
consider CRRT to be appropriate for patients with
haemodynamic instability, fluid overload, catabolism,
or sepsis with AKI.
CRRT is also indicated in any patient who meets
the criteria for IH but cannot undergo this procedure
because of haemodynamic instability (Augustine et al,
2004). As noted, a large-bore, double-lumen catheter is
typically used for CRRT. The preferred site of catheter
insertion is the right internal jugular vein. The catheter
should be inserted with the use of ultrasonographic
guidance and with adherence to infection-control
policies (Hassan et al, 2008).
The use of tunnelled catheters is warranted in
patients who require prolonged RRT (> 1 –3 weeks)
and is associated with a lower rate of infection
and thrombosis than the rate associated with non-
tunnelled catheters (Coryell et al, 2009). There are
currently insufficient data to recommend one form
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19/02/2013 11:20
 practice

of CRRT over another. In continuous venovenous study the daily cost of CRRT ranged from £318 to
haemodialysis, the rate of removal of solutes (by £467 depending on the form of treatment and the
diffusion) is inversely proportional to their molecular anticoagulant used (Manns et al, 2003). In another
weight, so that larger molecules are cleared relatively analysis the average cost of CRRT per patient was
inefficiently. In contrast, in continuous venovenous calculated to be the equivalent of £5 140 over a mean
haemofiltration, the rate of removal of solutes (by length of stay of 17 days (Rauf et al, 2003).
convection) is dependent only on the size of the pores
in the membrane. As a result, many clinicians prefer Solutions
to use continuous venovenous haemofiltration (or Solutions used in CRRT should be chosen to restore
continuous venovenous haemodiafiltration) in the the acid–base balance and maintain physiologic
belief that convection can more effectively reduce the electrolyte concentrations. In general, replacement
effects of systemic inflammatory response syndrome by and dialysate solutions should contain glucose and
removing cytokines, most of which are in the middle electrolytes (generally including sodium, potassium,
molecular-weight range. calcium and magnesium) in concentrations that are in
CRRT can be discontinued once renal recovery has physiologic ranges. Adjustments of electrolytes may be
been confirmed or the decision is made to switch to needed depending on specific clinical circumstances.
another form of renal replacement because of the In addition, continuous renal replacement solutions
patient’s clinical condition. For example, a switch require a buffer anion because of loss of bicarbonate
to IH may be appropriate if the patient is weaned through the haemofilter. Although acetate, lactate,
off vasocontricting agents, needs to mobilise, or is citrate and bicarbonate have all been used for this
transferred out of the ICU. [AQ5. Before introducing purpose, bicarbonate is currently the preferred buffer.
the following data on cost, can you provide a The clearance of small solutes with CRRT is a
general statement about the costliness of CRRT? function of effluent flow. The effluent comprises
Perhaps in contrast to other methods] In one the ultrafiltrate in continuous venovenous
haemofiltration, spent dialysate in continuous
venovenous haemodialysis, and both in continuous
venovenous haemodiafiltration. Therefore, effluent
Table 1.Types of continous renal replacement therapy flow is commonly used as a measure of the ‘dose’
Acronym Method Description Type of RRT administered (Palevsky et al, 2009). Studies
CVVH Continuous The therapy is indicated for uraemia, Form of suggest that an effluent flow rate of at least 20–25 ml
venovenous severe pH or electrolyte imbalance convective per kilogram per hour is necessary for adequate
haemofiltration with or without fluid overload. dialysis solute clearance (Bellomo et al, 2009).
Ultrafiltration rate is high, and
replacement electrolyte solution is Circuit downtime
required to maintain haemodynamic Because of circuit downtime only 68% of patients
stability.This treatment is also very received their prescribed dose of CRRT [AQ6. In a
effective for clearing mid-sized study in what setting? with what numbers? Can
molecules and may play a role in you introduce this statement, e.g. ‘Circuit downtime
improving outcomes in sepsis. can be a problem/is common(?) in CRRT; in a study
CVVHD Continuous The dialysate is infused in a Continuous by Venkataraman et al it was found that the most
venovenous counter-current flow to the blood diffusive dialysis common’...?](Venkataraman et al, 2002). The most
haemodialysis on the extra-capillary area of the common cause of treatment interruption is clotting of
filter. This provides reasonably the circuit. While CRRT can be administered without
effective solute clearance, although anticoagulation, particularly in patients with an
mostly small molecules and excess increased risk of bleeding, this approach is generally
fluid are removed. associated with low success rates. Unfractionated
CVVHDF Continuous The dialysate is driven in a direction Combines heparin is the most commonly used anticoagulant.
venovenous counter-current to the blood on convective and Because of the risk of bleeding associated with heparin
haemodiafiltration the extra-capillary area of the filter diffusive dialysis and concern about the development of heparin-
and replacement fluid is used either induced thrombocytopenia, the use of regional citrate
before or after the filter. Both small anticoagulation has been increasing (Tolwani and
and middle molecules are cleared. Wille, 2009).
The use of replacement fluid allows Clotting can also be promoted or prevented
adequate solute removal even with by the technical aspects of therapy. For instance,
zero or positive net fluid balance. in continuous venovenous haemofiltration, the
administration of replacement fluid before the

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haemofilter dilutes the blood in the filter, which
reduces clotting, whereas administration of the
replacement fluid after the haemofilter concentrates
the blood in the filter and enhances clotting. Another
option is to use higher blood flows. Although blood-
flow rates of 100–150 ml per minute were common in
the past, many clinicians are now using blood-flow
rates of 200–250 ml per minute to reduce the risk of
thrombosis (Clark et al, 2003).
Complications
Complications of vascular access, including infection
and vascular injury, are a common concern with CRRT.
These complications are reported to occur in 5–19%
of patients, depending on the access site selected
(Merrer et al, 2001). Arterial puncture, haematoma,
haemothorax and pneumothorax are the most
common complications reported. Arteriovenous
fistulas, aneurysms, thrombus formation, pericardial
tamponade, and retroperitoneal haemorrhage have
also been described (Oliver, 2001).
During therapy, meticulous monitoring of machine
performance and of the patient’s electrolytes and
haemodynamics are required to prevent complications.
Common problems include hypotension, arrhythmias,
fluid-balance and electrolyte disturbances, nutrient
losses, hypothermia, and bleeding complications
from anticoagulation (Shingarev et al, 2011). CRRT
can result in clinically significant hypokalaemia
and hypophosphatemia, which may lead to severe
complications if uncorrected. Hypothermia can be
mitigated with the use of a blood or fluid warmer.
Another serious concern is potential under-dosing
of drugs. There are no clear data on the appropriate
dosing of many drugs during CRRT; this is of particular
concern with the use of antibiotics. Doses of antibiotics
that are too low can result in inadequate treatment
of sepsis; doses that are too high can lead to systemic
exposure and toxicity. To ensure efficacy and prevent
toxicity, drug monitoring is highly recommended.
Conclusion
CRRT is used if a patient is critically ill with AKI.
The goal is to replace, as best as possible, the lost
function of kidneys, by providing slow and balanced
fluid removal for patients. Different variations of the
technique exist for different patients. The science
behind the technique is relatively complex and the
equipment used is expensive and sophisticated, yet
requires regular monitoring. The methodology is
not without potential complications, but careful
supervision of the patient should reduce the likelihood
of such problems arising.
Acknowledgement
The author would like to acknowledge the importance of the article by
vol 5 no 3 March 2013 journal of renal nursing
JRN_5_2_CRRT_edit.indd 41
practice
Table 2. Indications and contraindications for continuous renal
replacement therapy (CRRT)
Indications
Classic indications
nn Hyperkalaemia
nn Severe metabolic acidosis
nn Diuretic-resistant volume overload
nn Oliguria or anuria
nn Uraemic complications
nn Some drug intoxications
Potential indications
nn Haemodynamic instability
nn Disrupted fluid balance (due to cardiac failure or multiorgan failure)
nn Increased catabolic states (e.g. rhabdomyolysis)
nn Sepsis
nn Increased intracranial pressure
nn Electrolyte abnormalities
Contraindications
nn Advance directives indicating that the patient does not want dialysis
nn The patient or his or her health care proxy declines CRRT
nn Inability to establish vascular access
nn Lack of appropriate infrastructure and trained personnel for CRRT
Tolwani (2012) in the writing of this review.
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 practice

Key points
nn Treatment of acute kidney injury (AKI) is chiefly limited to supportive measures,
including renal replacement therapy (RRT)
nn Continuous renal replacement therapy (CRRT) is a form of RRT that involves a
spectrum of dialysis methods, which make use of convection, diffusion, or a mixture
of both, in solute removal
nn The benefits of CRRT over intermittent haemodialysis in AKI patients include
improved haemodynamic tolerance, and the potential to reduce the effects of
systemic inflammatory response syndrome
nn Use of CRRT requires careful monitoring and is not without complications, which all
clinicians must be aware of

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