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Renal Replacement Therapy: A Practical Approach

Chapter · May 2018

DOI: 10.1007/978-3-319-71712-8_28

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 Renal Replacement Therapy
in the Critically Ill Surgical Patient 15
Kevin K. Chung and Ian J. Stewart

Introduction on how long the therapy is applied and what type of machine
is used. Regardless of the length of therapy, it is important to
The diagnosis of clinically significant acute kidney injury differentiate the two different ways that solutes can be
(AKI) among the critically ill surgical population occurs in cleared through a hemofilter within the context of an extra-
approximately one in four admissions [1]. About 5 % of all corporeal circuit. The two modes of clearance are “diffusive
patients admitted to the intensive care unit (ICU), or 1 out of clearance” (a.k.a. hemodialysis) and “convective clearance”
every 20 admissions, require some form of renal replacement (a.k.a. hemofiltration). Before being able to understand this
therapy (RRT) [1]. Among all critically ill patients who difference, we must understand the anatomy of a hemofilter,
require RRT, the mortality has consistently been around which does not differ significantly regardless of “mode.”
60 % [2]. Practically speaking, RRT refers to the clearance of
excessive electrolytes, toxic solutes, and volume that accu-
mulates in the intravascular and extravascular space in the Hemofilter Anatomy
setting of AKI. Most often, this type of therapy is delivered
via a venovenous extracorporeal circuit with a blood pump Standard hemofilters that are utilized for the purposes of
that drives venous blood through an artificial “kidney” mem- RRT are comprised of thousands of parallel hollow fibers
brane. Less commonly, the peritoneal cavity could be used to encased in a cylindrical casing through which blood can flow
exchange electrolytes and solutes in the form of peritoneal (Fig. 15.1). These hollow fibers are analogous to tiny garden
dialysis. We will focus our discussion in this chapter mainly hoses with semipermeable walls, allowing small solutes and
on extracorporeal RRT with only a brief section on perito- fluid to leak through the walls while blood is contained and
neal dialysis. passes through the middle portion of the fibers. In between
the individual fibers naturally exists the “interstitial space”
where leaked solutes can then escape through an opening in
Overview of Modalities the cylindrical casing through the generation of a steady neg-
ative pressure or hydrostatic pressure alone.
There are a number of RRT “modes” that can be used in the
ICU. The various modes are typically divided into continu- Hemodialysis (Diffusive Clearance)
ous RRT (CRRT) or intermittent hemodialysis (IHD) based As blood flows through the fibers of a standard hemofilter, a
port exists on one end of the outer cylindrical casing through
which an electrolyte balanced solution (dialysate) can be
The opinions or assertions contained herein are the private views of the infused to bathe the “interstitial space” and exit through
author and are not to be construed as official or as reflecting the views another port on the other end of the outer casing. The steady
of the Department of the Army or the Department of Defense. flow of dialysate through this space creates a gradient
K.K. Chung, MD (*) between the concentration of any given electrolyte or solute
Burn Center, US Army Institute of Surgical Research, in the blood contained in the hollow fibers and the concentra-
Fort Sam Houston, TX 78258, USA
tion of the electrolyte or solute contained in the dialysate in
e-mail: [email protected]
the interstitial space. This concentration gradient allows sol-
I.J. Stewart, MD
utes to passively move across the semipermeable membrane,
Department of Medicine, David Grant Medical Center,
Travis AFB, CA 94535, USA from the space of high concentration, in the blood, to the
e-mail: [email protected] space of low concentration, in the dialysate (Fig. 15.2). To

© Springer International Publishing Switzerland 2016 159

N.D. Martin, L.J. Kaplan (eds.), Principles of Adult Surgical Critical Care, DOI 10.1007/978-3-319-33341-0_15

[email protected]
160 K.K. Chung and I.J. Stewart

Fig. 15.1 (a) Schematic of a a b

hemofilter used in this case
for hemodialysis. The
patient’s blood enters the
device at the top and is
distributed into a multitude of Blood in
semipermeable hollow fibers,
demonstrated by the → Dialysate out
cross-sectional view (b). The
patient’s blood exists the
filter at the bottom and is

Hemofilter
returned. Dialysate flows in a
countercurrent fashion (i.e.,
the opposite direction of
blood flow) to optimize the
concentration gradient across
the entire length of the
hemofilter ← Dialysate in
Blood out

Cross sectional view of hemofilter

Blood
optimize the gradient between the two compartments, the
dialysate is run in a countercurrent fashion (i.e., the blood
and dialysate flow in opposite directions). This movement of
solutes across a membrane down the concentration gradient
is described as “diffusive clearance.” Simply, dialysis
removes various excess solutes from the bloodstream by
maintaining a gradient to optimize “diffusion.” Although
highly efficient, this mode of clearance targets mostly solutes
and molecules that are of low molecular weight in size
(i.e., ≤10 kDal). Potassium and urea are examples of
molecules that are in this range. Depending on the type
of machine utilized, dialysate can be generated through the
machine (IHD machines), come in premixed bags, or mixed
by the hospital pharmacy.

Hemofiltration (Convective Clearance)

Hemofiltration, on the other hand, is a mode of solute
removal that utilizes “convective clearance.” In this mode, a
negative pressure is generated in the interstitial space of the
hemofilter, actively pulling solutes across the semiperme-
Dialysate
able membrane while an electrolyte balanced solution is
introduced simultaneously either into the extracorporeal cir-
Fig. 15.2 Schematic representation of diffuse clearance in the cuit or into the venous system of the body at the same rate
setting of hemodialysis. Large particles (such as cells or albumin) are (Fig. 15.3). This fluid is appropriately designated as
represented by the red circles. As these particles are too large to fit
“replacement fluid.” Replacement fluid solutions are typi-
through the pores of the semipermeable membrane, they pass through
the hemofilter and are returned to the patients. Small molecules (such cally premade and commercially available in sterile packag-
as potassium and urea) are represented by the black circles. These ing from various CRRT vendors. Alternatively, balanced
molecules flow down their concentration gradient across the crystalloid solutions, such as PlasmaLyte A® (Baxter
semipermeable membrane from the blood space to the interstitial
Healthcare Corporation, Deerfield, IL), can be utilized as
space. To optimize the concentration gradient across the length of the
hemofilter, the blood and dialysate go in opposite directions replacement solution. Of note, dialysate that is generated by
(countercurrent) IHD machines, typically through a reverse osmosis system

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15 Renal Replacement Therapy in the Critically Ill Surgical Patient 161

Blood advantageous in patients that require high clearance (such as

severe crush injury with rhabdomyolysis and resultant hyper-
kalemia). However, IHD may not be the preferred modality
in critically ill surgical patients, because it can result in more
hemodynamic instability than CRRT via two mechanisms.
The first mechanism is due to the high clearance of IHD with
resultant decrease in plasma osmolality [3]. When solute is
removed from the intravascular space, equilibration from the
extravascular space is not immediate. This establishes a gra-
dient between these two compartments. Via oncotic pres-
sure, water will flow out of the intravascular space leading to
decreased blood volume. The second mechanism is due to
the short treatment time during which volume can be
removed. Similar to solute, equilibration of volume from the
extravascular to the intravascular space is not immediate, and
ultrafiltration can result in decreased blood volume. The rate
at which volume is removed is therefore a key determinant in
how a treatment is hemodynamically tolerated. For example,
if 2 L of volume needs to be removed, the rate at which this
occurs during a 4 h IHD treatment is 500 ml/h. This is much
Effluent greater than the rate of ~83 ml/h that could be achieved using
a continuous modality (2 L removed over 24 h). Therefore,
Fig. 15.3 Schematic representation of convective clearance in the set-
IHD should only be used on hemodynamically stable
ting of hemofiltration. With hemofiltration, there is no dialysate in the
interstitial space. Negative pressure in the interstitial space pulls both patients, unless high clearances are required, for example,
solvent and fluid across the semipermeable membrane. Replacement severe rhabdomyolysis with hyperkalemia that cannot be
fluid is infused either proximal to the hemofilter (pre-dilution) or distal maintained at a safe level with a continuous modality.
to the hemofilter (post-dilution)
Decreasing the rate at which fluid is removed, by either
increasing time or frequency, has been shown to decrease
utilizing tap water, cannot be utilized as replacement solu- intradialytic hypotension in outpatient IHD [4] and can be
tion as it is not considered “sterile.” considered in the critical care setting to minimize hemody-
Convective clearance, due to its active nature, can target namic instability.
solutes and molecules of higher molecular weight generally
described as “middle molecules” (i.e., – 10–50 kDal). Continuous Modalities
Examples of such molecules include beta2-microglobulin, Continuous modalities are typically delivered via machines
most drugs such as antimicrobials, and pro- and anti- that are specifically designed and marketed for inpatient use
inflammatory mediators such as interleukin-1, interleukin-6, as CRRT machines. Unlike IHD, these machines typically do
and interleukin-8. The ability of hemofiltration (convection) not utilize a water source (tap water) as they do not generate
to remove such molecules has direct implications in the way dialysate real time. Instead, the machines rely on premade
electrolytes are managed, how drugs are dosed, and may sterile solutions that can be utilized for the purposes of both
impart extrarenal benefits. hemodialysis and hemofiltration. In fact, the exact same bag
of solution can be labeled as “dialysate” or “replacement
Intermittent Hemodialysis fluid” based entirely on how the solution is employed. The
IHD describes a mode of extracorporeal therapy that is based four modes described below are all commonly grouped
on diffusive clearance and applied for a fixed period of time. under the term “CRRT.” See Table 15.1 for suggested initial
Generally, IHD utilizes the same machines, personnel (dialy- prescriptions.
sis technicians), and principles as chronic outpatient hemodi-
alysis. In IHD, clearance is dependent on the blood flow rate Slow Continuous Ultrafiltration (SCUF)
and the dialysate rate. Treatments in the ICU, lasting 2–4 h in In SCUF mode, a steady negative pressure is applied to the
length, are prescribed three to five times weekly. interstitial space pulling solutes and water across the semi-
Compared to CRRT, IHD results in much greater clear- permeable membrane and discarded through an opening in
ances because of higher dialysate flow rates. This may be the outer filter casing through a tube that leads to an empty

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162 K.K. Chung and I.J. Stewart

Table 15.1 Typical starting prescription for the various modes of CRRT
Ultrafiltrate rate
Mode Blood flow rate (BFR) Replacement fluid rate Dialysate flow rate (fluid removal)
SCUF 50–200 ml/min None None 50–500 ml/h
CVVH 100–400 ml/min 2–4 L/h None 0–500 ml/h
CVVHD 100–400 ml/min None 2–4 L/h 0–500 ml/h
CVVHDF 100–400 ml/min 1–2 L/h 1–2 L/h 0–500 ml/h

bag or directly into the sink. The fluid that is removed via contrast to CVVHD, these solutions, now termed “replace-
this method is called “ultrafiltrate” and consists of only the ment fluid,” are infused directly into the extracorporeal cir-
fluid that is pulled across the semipermeable membrane cuit and mixed directly with the circulating blood.
while blood moves through the hollow fibers. This mode is Simultaneously, the negative pressure exerted in the intersti-
typically prescribed to those who only need excess volume tial space in between the hollow fibers of the hemofilter gen-
removed as in the case of patients with diuretic resistant fluid erates solute drag across the semipermeable membrane,
overload. Use of this mode is uncommon for surgical ICU removing solutes and water as the same rate that replace-
patients as most have some degree of AKI and could benefit ment fluid is being infused. The replacement fluid infusion
from the solute balance that is achieved through the other can enter the circuit prefilter (proximal to the hemofilter),
CRRT modes. post-filter (distal to the hemofilter), or both depending on
the type of machine used. The advantage of prefilter infu-
Continuous Venovenous Hemodialysis (CVVHD) sion of replacement fluid is a prolonged filter life that results
CVVHD is a mode of extracorporeal therapy that is based on from the dilution of blood prior to its entrance into the
diffusive clearance and applied continuously. CVVHD, hemofilter. However, dilution of the blood also has the dis-
being a mode of CRRT, is delivered by machines specifically advantage of decreasing the efficiency of solute clearance.
designed for the ICU environment and utilizes premixed Post-filter infusion of replacement fluid optimizes efficiency
solutions. These solutions, typically in 5-L bags, are termed but increases the chance of hemofilter clotting. Some CRRT
“dialysate” since it is used to provide the concentration gra- machines allow the infusion of replacement fluid both pre-
dient necessary for diffusive clearance. and post-filter. Regardless of where the replacement fluid is
infused relative to the filter, an important concept to
Continuous Venovenous Hemofiltration (CVVH) emphasize is filtration fraction. In an effort to minimize the
CVVH is a mode of extracorporeal therapy that is based on hemoconcentration within the hollow fibers of the hemofil-
convective clearance and applied continuously. CVVH is ter, the filtration fraction must be kept below 25 %. Filtration
also delivered by machines specifically designed for the fraction is simply calculated by adding all the effluent
ICU environment and utilizes premixed solutions. In together and dividing it by the blood flow [5].

Filtration Fraction = Total effluent ( replacement fluid + ultrafiltrate ) / blood flow

The effluent consists of all the solute and water that is pulled clearance (hemofiltration) applied continuously. Thus, a 5-L
into the interstitial space and directed out of the hemofilter bag of premixed solution is connected to be infused as dialy-
casing into a waste bag or into a drain. This can be estimated sate, while another bag is connected to be infused as replace-
by adding the replacement fluid rate and the additional ultra- ment fluid. Although the same bag of solution, they are
filtrate set each hour. This equation is precise for post-filter appropriately labeled differently based on the function the
infusion of replacement fluid. Prefilter infusion would fur- solution performs.
ther lower the filtration fraction by partially diluting the
blood prior to it entering the hemofilter. Thus, this simple Hybrid Therapy: SLED
equation can be used as a rough estimate with the knowledge Slow low-efficiency dialysis (SLED) is a hybrid therapy of
that the actual filtration fraction will always be lower if any CRRT and IHD. In the literature, it is sometimes termed sus-
portion of the replacement fluid is given prefilter. tained low-efficiency dialysis, extended daily dialysis, or
prolonged intermittent renal replacement therapy. The main
Continuous Venovenous Hemodiafiltration advantages of SLED are that it can be performed with a con-
(CVVHDF) ventional IHD machine, does not require specialized equip-
CVVHDF is a mode of extracorporeal therapy that utilizes ment, and requires less anticoagulation [6]. The differences
both diffusive clearance (hemodialysis) and convective between SLED and IHD are flows and time. In SLED, the

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15 Renal Replacement Therapy in the Critically Ill Surgical Patient 163

dialysate and blood flows are usually 100–200 ml/min, while V being the volume of distribution of urea (in L, equal to total
in IHD the blood and dialysate flow rates are 350–400 ml/ body water). As the units (L and hour) cancel out, Kt/V is a
min and 700–800 ml/min, respectively. Conversely, while unit-less measure that describes the dose of IHD normalized
IHD is usually limited to 4 h, most SLED treatments last 8 h, for body size and time. Practically, this equates to a Kt/V of
but can be extended to 24 h which has been described as approximately 1.3 per IHD session for an every other day or
continuous SLED (C-SLED) [7]. Practically, C-SLED is no three times a week schedule. A Kt/V of 1.3 equates to a urea
different than CVVHD; however the former usually involves reduction ratio (URR) of at least 60 % (depending on patient
higher dialysate flow rates. Otherwise, the only difference is weight and ultrafiltration). Thus, if a patient is initiated on
that C-SLED is delivered using conventional outpatient IHD with a blood urea nitrogen (BUN) level of approximately
machines, while CVVHD is delivered using CRRT machines 100 mg/dL, the post-IHD level should be <40 mg/dL. For
that use premixed solutions. SLED allows for slower clear- clinical use, however, modern dialysis machines have built-in
ance of solute and volume, compared to IHD, which results conductivity sensors that can estimate Kt/V in real time. If this
in improved hemodynamic stability. The main disadvantage target dose is not achieved, the patient has been underdosed
to SLED, particularly when treatments last more than 8 h, is and could benefit from either more frequent IHD treatments
uncertainty regarding appropriate dosing of essential medi- or extended treatment times to achieve the minimum accept-
cations (such as antibiotics) [8]. Additionally, staffing longer able weekly dose recommended by KDIGO. For CRRT,
treatments for SLED becomes an issue if dialysis technician KDIGO recommends delivering a total effluent volume of
resources are limited. 20–25 ml/kg/h for AKI [10]. The total effluent volume con-
There is a paucity of evidence comparing SLED to sists of any fluid that flows through the interstitial space of the
CRRT. A recent meta-analysis examined 17 studies (7 ran- hemofilter to dump into the waste line into the effluent bag or
domized controlled trials and 10 observational studies) that into the sink. This can consist of ultrafiltrate only (SCUF),
compared SLED to CRRT [9]. The investigators found a effluent with or without ultrafiltrate (CVVH), dialysate with
trend toward lower mortality in the observational studies but or without ultrafiltrate (CVVHD), or dialysate plus effluent
no difference in mortality in the randomized trials. This trend with or without ultrafiltrate (CVVHDF). All commercially
toward improved outcomes with SLED in the observational available CRRT machines can display the total effluent vol-
studies should be interpreted with caution given the inherent ume (ml/kg/h) on the monitor.
bias in these types of studies. The meta-analysis also reported Multiple studies have demonstrated that increasing doses
no significant differences between CRRT and SLED in rates beyond that recommended by KDIGO for both IHD and CRRT
of renal recovery, fluid removal, length of ICU stay, clear- does not result in improved outcomes. The Veteran’s Affairs
ance, or vasopressor escalation. However, SLED was less and the National Institutes of Health Acute Renal Failure Trial
expensive in all three of the studies that reported on cost. Network study (ATN study) evaluated RRT dose in 1,124
patients [11]. The trial randomized patients needing RRT to
either an intensive regimen of RRT or a less intense regimen.
Overview of Controversies The intervention in the intensive group consisted of six ses-
sions of IHD per week for hemodynamically stable patients
Dose and CVVHDF at a dose of 35 ml/kg/h or daily SLED for unsta-
ble patients. The less intensive group received three sessions of
Providers regularly prescribing or caring for critically ill IHD per week for hemodynamically stable patients and
patients on RRT must pay close attention to the dose of ther- CVVHDF at a dose of 20 ml/kg/h or every other day SLED for
apy. The Kidney Disease: Improving Global Outcomes unstable patients. The Australian and New Zealand Intensive
(KDIGO) guidelines recommends frequent assessment of the Care Society (ANZICS) Clinical Trials Group conducted their
prescription of and the delivery of actual dose [10]. At a mini- own multicenter trial, called the Randomized Evaluation of
mum, RRT applied in the critically ill surgical patient should Normal versus Augmented Level RRT study (RENAL study)
be able to achieve correction of any metabolic derangement comparing high-dose CVVHDF (40 ml/kg/h) to lower-dose
or fluid imbalance for which the therapy was initiated. The CVVHDF (25 ml/kg/h) in 1,508 patients [12]. Neither the ATN
nomenclature used for the dosing of RRT differs when study nor the RENAL study demonstrated a survival advantage
describing IHD and CRRT. It should be noted that the highest to delivering a higher dose of RRT regardless of mode.
grades (1A) were assigned for both dosing recommendations,
reflecting strength and quality of the evidence that exists to
result in those recommendations. For IHD, the KDIGO Mode
guidelines recommend delivering a Kt/V of at least 3.9 per
week when prescribing either IHD or SLED in AKI [10]. The optimal mode of RRT in the treatment of surgical ICU
Kt/V is a measure of the fractional clearance of urea, with K patients has been the subject of much debate. As mentioned
being the urea clearance (in L/h), t being time (in hours), and above, CRRT offers the advantage of being better tolerated

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164 K.K. Chung and I.J. Stewart

in hemodynamically unstable patients while allowing for suggest that early initiation in the critically ill is no better
slow and steady removal of volume over time when needed. than waiting for clinical scenarios that would prompt the ini-
However, a disadvantage is the need for continuous antico- tiation of RRT in outpatients with chronic kidney disease
agulation that increases the need for monitoring and, in turn, who develop fluid overload or a metabolic disturbance of
increases workload. IHD offers the advantage of rapid solute some kind (electrolyte imbalance, uremia, or acidosis) [24].
removal and rapid correction of electrolytes. There is also A recent systematic review suggested a possible beneficial
virtually no need for regional anticoagulation, and the inter- impact on survival but concluded that the evidence was weak
mittent nature of the therapy allows time for certain proce- at best to make a strong recommendation [25]. Perhaps stud-
dures and diagnostics without the need to interrupt therapy. ies that are currently enrolling patients will help shed more
Disadvantages of IHD include the potential for sudden fluid clarity on this topic and help inform the nephrology and criti-
shifts which can be harmful in certain populations such as cal care community [26, 27]. Currently the KDIGO recom-
those with traumatic brain injury [13] with increased intra- mendation strongly encourages clinicians to consider the
cranial pressures and the potential for hemodynamic insta- broader clinical context while identifying the specific condi-
bility. The potential for hemodynamic instability can be tions that can potentially be modified with RRT when con-
mitigated by converting IHD to SLED and may be done sidering initiation [10].
seamlessly as long as staffing is available. CRRT is preferred
in patients with brain injury because of the lower clearance
offered by that mode. If CRRT is not available, SLED is an Clinical Considerations
alternate mode for these patients. However, since SLED gen-
erally has larger clearances than CRRT potentially resulting Access
in a greater osmotic shift, CRRT is the preferred modality if
available. The KDIGO guidelines [10] suggest that RRT in the ICU
Despite the theoretical advantages of one mode versus setting be initiated with an un-cuffed, non-tunneled dialysis
another, studies have demonstrated that at equivalent doses, catheter. As has become the standard of practice, ultrasound
no short-term survival advantage exists when comparing guidance should be used for line insertion. The KDIGO
IHD to CRRT [14]. The KDIGO guidelines view IHD and guidelines recommend that access be preferentially placed in
CRRT as “complementary therapies” in the management of the right internal jugular vein. The second choice is a femo-
AKI in the ICU [10]. We are biased in favor of CRRT in most ral vein and the third choice is the left internal jugular vein.
surgical ICU patients for the following reasons. First, This recommendation is based on balancing the need for
KDIGO recommends choosing CRRT over IHD in hemody- adequate RRT and the infectious risk associated with central
namically unstable patients [10]. In many surgical ICU line placement. The right internal jugular vein is preferred
patient populations, such as burns [15], cardiothoracic [16, because it is associated with the least amount of catheter dys-
17], or liver transplants [18], hemodynamic instability com- function (defined as the ability to maintain adequate blood
monly accompanies acute care needs. Second, patients with flows) [28]. However, this was only a trend (p = 0.09) for
intracranial hypertension from brain edema from any cause femoral catheters compared to right internal jugular cathe-
with AKI should be managed with CRRT over IHD [10, 13]. ters. Clearance also appears to be equivalent between femo-
Lastly, long-term follow up studies, published after the ral and jugular catheters as long as a 25-cm catheter is used
KDIGO guidelines, suggest a possible advantage to a CRRT- in the femoral vein. Conversely, the left internal jugular is
based strategy in the ICU as less patients appear to be dialy- associated with the most catheter dysfunction [28]. A con-
sis dependent when compared to an IHD-based strategy [19, cern with the use of femoral access is catheter-related blood-
20]. It is quite compelling that among ATN trial survivors, stream infection. However, in a randomized trial, femoral
the presence of dialysis dependence at discharge was 25 %, catheters were not associated with an increased risk of infec-
while among RENAL trial survivors, only 5 % of survivors tion except in overweight patients (BMI >28.4) [29].
were dialysis dependent [21, 22]. Thus, CRRT may be the The use of subclavian catheters is discouraged in patients
therapy of choice in most surgical ICU patients. with AKI on RRT [10]. Because critically ill patients that
require RRT are at an increased risk of developing end-stage
renal disease [30], they may require permanent IHD access in
Timing the future. Central venous lines in the subclavian can cause
central venous stenosis [31], which can complicate subsequent
The optimal time to initiate RRT in the critically ill surgical arteriovenous fistula placement. Therefore, the subclavian
patient with AKI is also a controversial topic. Early studies should only be used for access if no other options exist and, if
showed benefit but were small in sample size [23]. Others needed, should be inserted on the dominant side [10].

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15 Renal Replacement Therapy in the Critically Ill Surgical Patient 165

Anticoagulation [37–39]. We agree that regional citrate should be considered

first line for anticoagulation in CRRT. However, given the
While anticoagulation may be deferred in certain situations, lack of standardized, approved citrate solutions and proto-
such as patients with a coagulopathy or other contraindica- cols, this should only be done at centers where physicians
tions, it is commonly used to prevent clotting of the filter. and nursing staff are comfortable with the technique.
Filter clotting can decrease the amount of time on RRT, Other anticoagulants such as argatroban can be used in
which impacts the delivered dose, and can also result in the setting of heparin-induced thrombocytopenia, which
blood loss with subsequent transfusion requirement. If a requires systemic anticoagulation. One study used a loading
patient requires systemic anticoagulation for another indica- dose of 100 μg/kg followed by a maintenance infusion of
tion (such as a deep vein thrombosis or pulmonary embo- 1 μg/kg/min [40]. This maintenance dose was then titrated
lism), it is adequate for the purposes of RRT. Otherwise, by 0.25 μg/kg/min to achieve a 1.5- to 3.0-fold elevation in
specific anticoagulation for the RRT circuit should be aPTT. The authors found that measures of illness severity
considered. (APACHE II and SAPS II) could be used to predict the
The most commonly used anticoagulants used to prevent required maintenance dose. If argatroban is contraindicated,
clotting of RRT circuits are heparin and citrate. When hepa- such as with severe liver failure, bivalirudin can also be used
rin is used, a bolus of 2,000–5,000 units (or 30 international for anticoagulation in a CRRT circuit [41].
units/kg) can be considered, followed by a continuous infu-
sion to maintain aPTT 1.5–2.0 times normal [32]. In patients
with an elevation in aPTT at baseline (PTT > 35 s), the initial General Antimicrobial Dosing for RRT
bolus can be deferred [33]. While a variety of citrate proto- Recommendations (Table 15.2)
cols have been described [34], the underlying concept is the
same; citrate binds to calcium, decreasing the ionized cal- Optimal dosing varies based on agent, hemofilter, mode,
cium concentration. Because calcium is a key cofactor in the dose, and patient characteristics which include protein bind-
clotting cascade, this prevents filter clotting [35]. To avoid ing, sieving coefficient, mode and dose of therapy, and vol-
systemic hypocalcemia, calcium is infused in either the ume of distribution. Please consult a critical care
venous return line or centrally. When using citrate anticoag- pharmacologist for more accurate initial dosing, mainte-
ulation, the replacement fluid or dialysate should have a cal- nance, and monitoring.
cium concentration of 0 to avoid increasing the ionized
calcium concentration within the circuit and reversing the
anticoagulant effect. If a hypertonic solution compared to Special Considerations
plasma is used, such as trisodium citrate (408 meq/L of
sodium), the replacement fluid should be slightly hypotonic. As already discussed, in the setting of traumatic brain injury,
Citrate also binds magnesium, therefore extra supplementa- or other causes of increased intracranial pressure, CRRT is
tion in the dialysate or replacement fluid should be consid- preferred over IHD. Greater clearance of IHD is not tolerated
ered. As citrate is metabolized predominantly by the liver to as well as CRRT from a hemodynamic standpoint. In the set-
bicarbonate, the bicarbonate concentration should also be ting of increase intracranial pressure, this can result in
lowered to avoid alkalemia. If the citrate is not metabolized, decreased cerebral perfusion pressure and increased brain
such as in the setting of liver failure or profound hypoperfu- edema [13, 44, 45]. Another factor in patients with brain
sion, citrate toxicity can occur. Citrate toxicity is character- injury is anticoagulation. Systemic anticoagulation should
ized by an anion gap metabolic acidosis and a total to ionized be avoided in favor of no anticoagulation or regional citrate
calcium ratio of >2.5 (note that units must be equivalent). anticoagulation [44]. The final factor to consider in patients
There are no citrate solutions that are approved by the Food with brain injury is the serum sodium, which is usually kept
and Drug Administration for anticoagulating an RRT circuit. artificially high to decrease edema. Commercially available
In the United States, this requires the use of hypertonic solutions have fixed sodium concentrations, therefore addi-
citrate intended for blood banking purposes [36]. tional hypertonic infusions of sodium should be given to
The optimal method for anticoagulation in RRT is not maintain sodium at goal. For these reasons, CRRT is clearly
defined. On the basis of clinical trials demonstrating longer the preferred modality in these patients.
filter life and less bleeding complications, the KDIGO guide- Peritoneal dialysis (PD) is a form of RRT that utilizes the
lines recommend citrate over heparin if the former is not peritoneal membrane to achieve clearance via diffusion with
contraindicated [10]. Since these guidelines were published fluid in the peritoneal space. The International Society for
in 2012, several other studies that compared heparin to citrate Peritoneal Dialysis (ISPD) has recently published guidelines
for anticoagulation have broadly confirmed these findings for PD in the setting of AKI [46]. In the setting of AKI, it is

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166 K.K. Chung and I.J. Stewart

Table 15.2 General antimicrobial dosing for RRT recommendations

Antibiotic IHD SLEDc CRRTe
Vancomycin 15–25 mg/kg loading dose, 20 mg/kg loading dosed 15–20 mg/kg loading dosed
then 500–1,000 mg after each
IHDa
Daptomycin 4–6 mg/kg every 48–72 h, 6 mg/kg every 24 h, give 8 mg/kg every 48 h
give after IHD on dialysis 2–12 h before treatment
days
Piperacillin/tazobactam 2.25 g every 8–12 h, give 4.5 g every 8 h, infuse each 3.375 g every 6 h, infuse each
after IHD on dialysis days dose over 4 h dose over 3 h
Cefepime 1,000 mg q 24 h, give after Not defined Loading dose of 2,000 mg,
IHD on dialysis days then 1,000–2,000 mg every
12 h
Meropenem 500 mg every 24 h, give after 500–1,000 mg every 8 h, 1,000 mg every 8 h
IHD on dialysis days time to infuse after end of
treatment
Imipenem/cilastatin 250–500 mg every 12 h Not defined Loading dose of 1,000 mg,
then 500 mg every 6–8 h
Levofloxacin 250–500 mg every 48 h 250–500 mg every 24 h Loading dose of 500–750 mg,
then 250 mg every 24 h
Amikacin 5–7.5 mg/kg every 48–72 hb Not defined, dose based on Loading dose of 10 mg/kg,
drug level then 7.5 mg/kg every
24–48 hf
Modified from Scoville et al. [8] Additional references: Heintz et al. [42] and Jamal et al. [43]
a
Redosing based on pre-IHD drug levels: <10 mg/L give 1,000 mg after IHD; 10–25 mg/L give 500–750 mg after IHD; >25 mg hold
b
Redose when based on levels: Pre-IHD <10 mg/L; post-IHD <6–8 mg/L
c
Assumes treatment for 8 h per day with blood and dialysate flow rates of 160 ml/min
d
Give supplemental doses for goal trough of 15–20 mg/L
e
Assumes effluent rate (sum of dialysate flow rate, replacement fluid and ultrafiltrate) of 25 ml/kg/h or 2 L per hour
f
For severe infection, monitor level with goal peak concentration of 15–30 mg/L, redose when <10 mg/L

more commonly used in the developing world owing to its Novel anticoagulants used in the outpatient setting for atrial
low cost compared to CRRT [46]. While there is limited fibrillation, deep vein thrombosis, and pulmonary embolism
evidence examining outcomes between PD and extracorpo- may be encountered in the surgical ICU. One such is the direct
real RRT methods, there is no evidence that one is superior thrombin inhibitor dabigatran. As there is no approved rever-
to the other in terms of mortality [47]. When compared to sal agent for dabigatran, and the drug is cleared renally [50],
CVVHDF, PD was not as effective in terms of creatinine and these patients can present a therapeutic dilemma when they
urea clearance or volume control [48]. However, the thera- present with AKI. Dabigatran can be cleared by hemodialysis
pies were similar in terms of control of hyperkalemia and [50, 51] and hemodialysis has been shown to decrease the
impact upon hemodynamics. Therefore, in an environment anticoagulant effect [51, 52]. As would be expected given the
where IHD and CRRT are not available, PD should be con- higher clearances inherent in IHD compared to CRRT, agent
sidered for the primary management of severe AKI requiring removal is higher with IHD [53]. Therefore, we suggest rapid
RRT. In patients with impaired ability to convert lactate, initiation of IHD in patients with life-threatening bleeding in
such as liver failure or shock, bicarbonate-containing solu- the setting of impaired renal function. Treatments longer than
tions are preferred over lactate-containing solutions as the 4 h may be required to sufficiently clear the agent to have a
former more rapidly corrects acidemia [49]. clinically relevant effect [52, 53].
PD is also a method of home hemodialysis used for the
chronic management of end-stage renal disease. Given
changes to the way in which Medicare reimburses nephrolo- Discontinuation of Therapy
gists, it is likely that this form of chronic RRT will become
more prominent in the United States and thus may be encoun- No specific guidelines exist for when to stop CRRT in the
tered in the surgical ICU more frequently. We suggest that, if setting of AKI. The KDIGO Guidelines recommend stop-
possible, PD be continued in such patients if they are admit- ping RRT when “it is no longer required, either because
ted to the surgical ICU. However, if patients are catabolic, intrinsic kidney function has recovered to the point that it is
requiring more clearance, or volume overloaded, they may adequate to meet patient needs or because RRT is no longer
need to be transitioned to another form of RRT. consistent with the goals of care” [10]. In our practice, we

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15 Renal Replacement Therapy in the Critically Ill Surgical Patient 167

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