Đề ôn thi thử môn hóa (131)

43  Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents

improvement in CRRT technology and high solute clearance, CRRT may also be used to rapidly
decrease potassium and endogenous or exogenous toxins. The main reason for the limited use
of IHD in AKI is the risk of hemodynamic compromise in ICU patients. IHD sessions tend to be
performed over short periods, relative to CRRT,
leading to hemodynamic instability when
attempting to achieve fluid removal goals in a
short time frame [64–66]. In some patients, rapid
solute clearance in a short time frame may
increase risk for dialysis disequilibrium syndrome. There is a need for nursing and nephrology expertise to perform IHD, access to a clean
water source, and specialized equipment. For
non-ICU hemodynamically stable patients with
AKI (e.g., acute interstitial nephritis, rhabdomyolysis), IHD is a treatment of choice.
Continuous Renal Replacement Therapy 
Continuous renal replacement therapy (CRRT)
provides more gradual and controlled ultrafiltration and solute clearance for hemodynamically unstable patients. CRRT allows for the
precise control of fluid removal in real time while
achieving a similar daily solute removal achieved
by IHD. This enables liberalized fluid administration (for medications and nutrition) and momentto-moment response to changes in clinical status.
CRRT technique is also feasible to teach to large
numbers of nurses; together with easily portable
machines and solutions, CRRT is ideal for ease
of use in the ICU setting. Data from the USA
multicenter Prospective Pediatric Continuous
Renal Replacement Therapy (ppCRRT) Registry
showed that CRRT is used safely across a wide
range of critically ill children [67], including
neonates (weight as low as 1.3 kg) and hemodynamically unstable patients. Despite recent technological advancements in many countries, CRRT
is performed utilizing machines designed for
adults with large extracorporeal circuit volumes.

This has stimulated development and currently
ongoing research on neonatal-specific CRRT
machines characterized by low extracorporeal
volumes, increased fluid precision, and ability to
use small vascular catheters [68–70]. CRRT has
also been considered to treat specific pediatric

841

populations, including those with sepsis or
undergoing cardiac surgery. Convective clearance
with CRRT may provide a theoretical benefit in
sepsis-induced AKI by enabling middle molecule
clearance and stabilizing the immune response
[71]; however, RCTs and observational studies in
adults and children have not demonstrated a clear
benefit [72, 73]. There has been interest in using
CRRT during cardiac surgery, specifically with
respect to use of “modified ultrafiltration.” The
goal of this practice is to limit FO development
and aid in removal of pro-inflammatory mediators.
The use of intraoperative modified ultrafiltration
in children undergoing cardiopulmonary bypass
remains an area of extraordinary center-based
practice variation and warrants further study [13].
CRRT with Extracorporeal Membrane
Oxygenation (ECMO)  Children treated with
ECMO are at very high risk of AKI (see
Epidemiology of AKI) [10]. Studies have shown
that these patients are at risk of FO, which is associated with increased mortality risk and length of

ECMO duration. About 20  years ago, Swaniker
et  al. reported that the ability to return to “dry
weight” was associated with improved survival.
There is consensus that CRRT aids with fluid
removal during ECMO and nutritional status and
is generally safe [74, 75]. In neonates, CRRT was
associated with reduced duration of ECMO by
24 h [76]. In an international survey by the KIDMO
group, treatment or prevention of FO was the
CRRT indication in 59% of patients treated with
ECMO [10]. The degree of FO at CRRT initiation
for children on ECMO is associated with increased
mortality [77]. Taken together, these data suggest
that children on ECMO may benefit from the early
initiation of RST on ECMO, and protocols describing this have been published [78]. Further studies
are needed to understand optimal use of CRRT in
this unique patient population. The technical
aspects of CRRT during ECMO will not be covered in this chapter. However, briefly, two methods
have been described. One is to add a hemofilter in
line within the ECMO circuit and run dialysis fluid
countercurrent to the blood flow using intravenous
pumps. Alternatively, and likely the best method,
is to add a CRRT machine in line to the ECMO


E. H. Ulrich et al.

842

circuit, typically pre-ECMO pump at the venous

end of the circuit. Additional anticoagulation is not
needed because ECMO requires systemic heparinization [79].

Table 43.6  Sample acute PD prescription
Fill
volume
Solution

 erforming Acute Peritoneal Dialysis
P
for AKI
The International Society for Peritoneal Dialysis
(ISPD) released guidelines for the use of peritoneal dialysis in AKI in 2014 for adults and children [80].

 ccess
A
A peritoneal dialysis catheter can be relatively
easy and safe to insert in the acute setting. PD
catheters are most commonly inserted surgically
using a Tenckhoff catheter; this method has the
lowest risk for catheter-related complications
and promotes higher-efficiency dialysis (ability
to deliver higher dialysis flow rates, maximizing
dwell times). Temporary catheters can also be
inserted percutaneously at the bedside. The drawback of this approach is the increased risk of PD
catheter site leakage, infection, and reduced efficacy given the requirement for low fill volumes.
Expertise is highly recommended for successful temporary catheter insertion. Complications
related to PD catheter insertion include bleeding
and infection; rarely, perforation of the bowel or
bladder can occur with insertion of rigid catheters. Perioperative antibiotics should be given for

surgical prophylaxis; a single dose of cefazolin is
the typical choice.
 cute Peritoneal Dialysis Prescription
A
(Table 43.6)
For acute PD, patients typically require starting
RST shortly after catheter insertion and catheter
flushing with dialysis solution containing heparin (500 units/L) until fluid is clear. Commercial
solutions are typically used containing sodium,
chloride, calcium, magnesium, buffer, and variable amounts of dextrose. At our centers, “physiologic” (neutral pH with bicarbonate buffer)
dextrose solutions are used. These solutions promote preservation of the peritoneal membrane in

Cycle
length

Total
dialysis
duration

10 mL/kg when
catheter is inserted
acutely
Commercially
available solution
(e.g., Physioneal®
1.36% or Dianeal®
1.5%) + heparin
500 units/L
Hourly cycles: 5-min
fill time, 45-min

dwell time, and
10-min drain time

Typically, 24 h in
infants and smaller
children

Depends on fluid
requirements and
other components
of dialysis
prescription (i.e.,
cycle length)
Cycle duration
can be reduced to
30 min for several
cycles to allow
rapid fluid
removal
Depends on
metabolic and
fluid requirements

the long term and reduce abdominal pain with filling. Heparin is added to the dialysis solution for a
minimum of 48–72 h in order to prevent catheter
obstruction with fibrin clot; heparin may be kept
in the dialysis solution bags for longer if there are
concerns or there is evidence of fibrin (the goal
being to reduce risk of catheter blockage).
With reduced time for wound healing, the risk

of catheter leakage is high; therefore, low dextrose solutions (Table  43.6) are used with low
fill volumes (10 mL/kg). Dextrose concentration
is increased to achieve required ultrafiltration
acutely; higher dextrose concentrations may be
needed to achieve ultrafiltration needs when low
fill volumes are used. Fill volumes are increased
gradually; if tunneled catheter insertion was
uncomplicated, fill volumes may be increased
over several days to 20–35  mL/kg with close
attention for catheter site leak. If there is leak,
dialysis may be held, and fluid cell counts and
cultures sent to rule out peritonitis (particularly
with evidence of leak) with or without empiric
antibiotic therapy.
With low fill volumes, manual intermittent
PD (IPD) can be performed 24 h/day; automated
PD (APD) with a cycler may be used with higher
fill volumes, often in non-ICU settings. In general, with low fill volumes, dwell durations are
short with approximately hourly cycles. If higher
ultrafiltration or solute clearance is needed,


43  Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents

dialysis solution dextrose concentration may be
increased, or cycle duration decreased (minimize
fluid absorption via the peritoneal membrane;
promote water and solute removal). Cycle durations as short as 30–45  min (dwell times ~15–
20 min) may help achieve rapid fluid removal and
solute clearance. Despite ISPD guideline recommendations, there is little data on ideal “dose” for

acute PD [57].

Complications
There is increased risk for poor efficiency dialysis
and ultrafiltration with acute PD due to use of low
fill volumes. Severely ill children may have poor
perfusion of the peritoneal membrane, which further reduces dialysis efficacy. As a result, patients
with severe metabolic disturbances (e.g., hyperammonemia) or FO may need to be considered for
alternative RST modalities (IHD or CRRT). Early
PD catheter insertion in high-risk patients to reduce
catheter-related complications is ideal, where possible. Of note, ultrafiltration may be unpredictable,
resulting in less precise fluid removal that can
result in dehydration and further renal injury [57],
mandating frequent assessment of ultrafiltration
and fluid balance after PD initiation.
Mechanical complications are similar to those
of chronic PD (leaks around the catheter, in the
subcutaneous tissue, or into pleural space; catheter kinking/malposition; catheter dysfunction due
to constipation or obstruction by clot or omentum; hernias). These complications are lower
with Tenckhoff catheters compared to rigid catheters. Tidal PD prescriptions are sometimes used
in patients with significant fill and drain pain. As
in chronic PD, vigilance for infection and use of
aseptic technique when handling the catheter and
performing dressing changes are crucial; this is
important to impress upon ICU healthcare teams
who may have limited experience with performing PD. Topical mupirocin ointment is applied to
the PD catheter exit site at our center to reduce
infection risk. Consideration for use of antifungal therapy (such as nystatin) should be made for
patients receiving antimicrobials.
Other complications include the risk of hyperglycemia with high glucose concentration solutions. There is also risk for malnutrition due

843

to PD-related protein loss and sodium disturbances associated with water and sodium losses.
Hypothermia may occur if the dialysis fluid is not
adequately warmed.
PD is fairly well tolerated from a hemodynamic perspective. Tidal PD prescriptions should
be considered in pre-load-dependent patients that
may not tolerate fill and drains. Patients with
respiratory distress or infants with severe gastroesophageal reflux may not tolerate large fill
volumes. Patients with prune belly syndrome and
ventriculo-peritoneal shunts can receive peritoneal dialysis; however, a history of other abdominal surgeries may make PD quite challenging.

Acute Hemodialysis for AKI
Although there has been significant shift away
from PD toward CRRT, the use of intermittent hemodialysis (IHD) in AKI has remained
relatively constant for the treatment of life-­
threatening emergencies (e.g., severe hyperkalemia; ingestions; hyperammonemia) or
non-critically ill patients with AKI.  A limited
discussion below will highlight unique aspects of
IHD in AKI; more detail is provided in chronic
hemodialysis chapters, and vascular access is discussed below in the CRRT section of this chapter.

 cute Hemodialysis Prescription
A
Acute IHD prescription is similar to initial prescription of chronic hemodialysis [81]. When
IHD is performed outside the HD unit, access
to water and use of a portable reverse osmosis
device are needed. Dialysis fluid prescription
is similar to that of chronic hemodialysis; prescribed potassium and phosphate concentration

should be based on patient labs. Biocompatible
dialyzers are used with a surface area close to
the body surface area of the child. Blood priming
of the circuit should be done if the extracorporeal volume is >10% of the total blood volume.
Dialysis flow rate is typically set at a standard
rate of 500 mL/min.
IHD for AKI is performed over a short period,
and rapid urea reduction can cause disequilibrium
syndrome (i.e., headache, cerebral edema, sei-


E. H. Ulrich et al.

844

zures, and potentially death). Although patients
with underlying CKD are at highest risk for disequilibrium syndrome, patients with AKI (especially if progression to RST need is over days to
weeks), very high blood urea nitrogen levels (e.g.,
>30 mmol/L), and concomitant risks for cerebral
edema (as often seen in ICU patients) may be at
risk. Rapid urea reduction should be avoided in
the first two to three IHD sessions. Some centers use slightly higher than usual dialysis fluid
sodium concentration (i.e., 145  mmol/L), and
most centers will administer intravenous mannitol
(0.5–1 g/kg over the first 1–2 h of IHD) if there is
concern for dialysis disequilibrium or blood urea
nitrogen levels are very high. At our centers, two
approaches are used to avoid rapid urea reduction
and disequilibrium syndrome in AKI. The first is

based on the fact that the primary determinant of
solute clearance with IHD is blood flow. Thus,
in the first IHD session for AKI, low blood flow
rates (e.g., ~2 mL/kg/min) are used, and duration
is short (2–2.5 h). In future sessions, blood flow
and IHD duration are gradually increased as tolerated. Another approach is based on (a) initially
aiming for urea reduction of 30%, which is relatively safe to avoid disequilibrium syndrome, (b)
using the known logarithmic relationship between
urea reduction and Kt/V (shown in Table 43.7) to
determine duration of the first IHD session, and
(c) slowly increasing urea reduction goals for
future IHD sessions using data from previous
IHD sessions (detailed in Table 43.7).
Fluid management when using IHD for AKI is
challenging for oligoanuric patients as daily fluid

Table 43.7  Example approach to prescribing urea reduction for acute hemodialysis
Step 1. Determine
urea reduction (UR)
goal for first IHD
session
and
Calculate first IHD
session duration
(minutes)

Logarithmic relationship between UR and Kt/V is:
− ln (post IHD urea concentration/pre ‐ urea concentration) = Kt/V
 
t = time (min)

 
V = volume = total body water in mL (consider patient age when calculating − this
parameter is estimated)
 
K = urea reduction coefficient in mL/min (based on dialyzer, QB, QD). Often similar to
blood flow, so if blood flow is 50 mL/min, K will often be 50 mL/min
First IHD treatment example:
UR goal is 30%: −ln(post IHD urea concentration/pre-urea concentration) = −ln(0.7) = 0.36
Using formula above, solve for t (minutes) or duration of first IHD treatment:
t  minutes of IHD  

Step 2. Recalculate
V (total body water
in mL) based on
previous IHD
session data
Step 3. Calculate t
(minutes) to achieve
desired UR for
future IHD sessions
(e.g., second, third)

ln  post urea / pre - urea   V  mL 
K  mL / min 

Ensure to order pre- and post-urea concentration testing for first 3–4 IHD treatments
Solve for V using equation above and data from previous session:
t  minutes of IHD of previous session   K  mL / min of previous IHDsession 
NewV  mL  
ln  post urea / pre - urea from the previous IHDsession 

 recalculated V  mL  to use for the current IHDsession.

Solve for t (minutes) of subsequent IHD treatments, using New (recalculated) V:
t  minutes of IHD  

ln  post urea / pre - urea   NewV  mL 
K  mL / min 

New V = V calculated in step 2, from data of previous IHD treatment.
Proposed UR goals for second and third IHD treatment:
Second IHD treatment
UR goal 50%: −ln(post urea/pre-urea) = −ln(0.5) = 0.69
Third IHD treatment
UR goal 70%: −ln(post urea/pre-urea) = −ln(0.3) = 1.2

ln natural logarithm function, IHD intermittent hemodialysis, QB blood flow rate (mL/min), QD dialysis flow rate,
(mL/min)


43  Diagnosis and Treatment of Acute Kidney Injury in Children and Adolescents

removal must be performed within a short session. Fluid restriction is often required. If IHD
is tolerated and safe with regard to urea reduction, longer IHD sessions may help achieve fluid
removal goals. In very hemodynamically stable
patients, ultrafiltration rate as high as ~0.2  mL/
kg/min (or 12 mL/kg/h) may be tolerated; however, in acutely ill patients, hypotension is common, limiting ability to achieve ultrafiltration
>1–3 mL/kg/h. Some centers use blood volume
monitoring software available with some dialysis
machines to help guide fluid removal.
As in chronic IHD, heparin anticoagulation

is used (10–20  units/kg bolus, followed by continuous infusion), and activated clotting time is
monitored. However, in many acute illnesses,
bleeding risk may be high, in which case IHD may
be performed without anticoagulation. This often
requires frequent flushing with normal saline to the
circuit pre-filter to prevent clotting. Administering
frequent fluid boluses to prevent clotting complicates fluid removal in infants, because this fluid
must be removed, which may not be tolerated in
small, sick children. For hemodynamically unstable patients, CRRT is thus a better option.

 ontinuous Renal Replacement
C
Therapy for AKI
CRRT offers several advantages, most importantly the delivery of highly precise therapy [82].
Gradual fluid removal offers improved hemodynamic stability and enables nutrition. CRRT provides more efficient clearance than PD, allowing
rapid correction of electrolyte and metabolic
disturbances. The major limitation of CRRT
­
has historically been requirement for technical
expertise; however, this barrier has decreased,
with simpler and safer machines adapted for use
in children [83].

Vascular Access (Table 43.8)
Vascular access is challenging in children, especially infants. However, it is key to administering
efficient CRRT, as access issues may lead to cessation of CRRT, circuit clotting, and, ultimately,
time off therapy.

845

Table 43.8  Vascular access for CRRT
Neck
lines

Femoral
lines

Weight
<5 kg
5 kg to
<20 kg
20 kg to
<35 kg
>35 kg
<5 kg

5 to
<20 kg

20 to
<40 kg
>40 kg

Cathetera
8Fr Medcomp Hemo-Cath
10Fr Medcomp Split
12Fr Medcomp
15.5Fr DuraMax
Palindrome
6.5Fr (10 cm) Gambro Gam

Cath (may sometimes be used
as a neck line in small
children)
8Fr (12.5 cm) Gambro Gam
Cath (5–15 kg)
10Fr (12 cm) Quinton
Mahurkar (15–20 kg)
10Fr (15 cm) Quinton
Mahurkar
11.5Fr (13.5 cm or 16 cm)
Quinton Mahurkar

Catheters used at the Hospital for Sick Children, Toronto,
Canada

a

Table 43.8 provides suggested catheter sizes
based on patient weight. Access insertion expertise is highly recommended in order to successfully insert catheters of adequate caliber to
enable adequate blood flow (lowest suggested
catheter size in Table 43.8 is a non-tunneled 6.5
French catheter). Different centers have access
to different catheters. It is important to be aware
of available catheters and to have tunneled and
un-tunneled catheter sizes appropriate for neonates, small, and larger children. Unsurprisingly,
larger catheters have been shown to be associated
with longer CRRT circuit survival, and use of
very small catheters (double lumen 5 French) is
associated with very low (<10 h) circuit survival
[84]. In very small patients (<5 kg), use of two

single-lumen catheters in two vessels has been
described [85].
Access placement location will be influenced by patient factors and by expertise of the
access inserter. Temporary or semi-permanent
(tunneled) catheters may be used. Temporary
catheters are often placed at the bedside. Neck
vessels (internal jugular vein) are preferred over
femoral veins, due to less recirculation (particularly in infants weighing <5 kg) and longer circuit survival associated with better blood flow


E. H. Ulrich et al.

846

rates and potentially reduced infection rates.
Femoral access should be considered a second
choice for insertion site, especially in patients
with high intra-abdominal pressure (may cause
elevated venous return pressures), patients who
are moving or combative, or patients who may
need these vessels for future renal transplantation. Subclavian veins should be avoided due to
the high risk of stenosis. Complications of vas-

cular access insertion include bleeding, infection, and air emboli; these are less common in
centers using ultrasound-guided access insertion.
Longer-term complications include vessel thrombosis or stenosis.

 RRT Machine and Modality (Fig. 43.3)
C
The first children treated with CRRT used continuous arteriovenous hemofiltration (CAVH) in

CVV H

From the patient

CVV H D

Return to the patient

From the patient

Dialysate

Effluent

Pre-filter
replacement

Return to the patient

Hemofilter

Post-filter
replacement

CVVHDF

From the patient

Fig. 43.3  Continuous renal replacement therapy extracorporeal circuit. Blood is pumped from the patient into

the hemofilter and is returned to the patient via a central
access, dual lumen dialysis line. With continuous venovenous hemofiltration (CVVH) (top left), blood flows
through the hemofilter; solutes and water are forced across
the semipermeable membrane by convection along a high-­
pressure hydrostatic gradient. Replacement fluid replenishes volume and electrolytes either pre-filter or post-filter.
With continuous venovenous hemodialysis (CVVHD)
(top right), blood flows through the hemofilter and dialysate fluid flows in the countercurrent direction. Solutes

Return to the patient

from the blood compartment move across the semipermeable membrane into the dialysate fluid compartment and
are removed by diffusion. Water moves via ultrafiltration
in the same direction. Cleared solutes and ultrafiltrate are
drained into the effluent bag. With continuous venovenous
hemodiafiltration (CVVHDF) (bottom), replacement and
dialysate fluids are both used to remove solutes and water
by a combination of diffusion, ultrafiltration, and convection. During citrate anticoagulation, citrate is infused
using the pre-filter replacement circuit or via a separate
intravenous pump to the pre-filter access port; calcium is
infused to the patient via a separate access line