Ebook Coté and Lerman''s a practice of anesthesia for infants and children (6/E): Part 2

SECTION VI

The Abdomen
OUTLINE
28 Essentials of Nephrology
29 General Abdominal and Urologic Surgery
30 Essentials of Hepatology
31 Organ Transplantation

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28

Essentials of Nephrology
Delbert R. Wigfall, John W. Foreman, Warwick A. Ames
Renal Physiology
Fluids and Electrolytes
Acid-Base Balance
Disease States
Acute Renal Failure and Acute Kidney Injury
Chronic Renal Failure
Preoperative Preparation of the Child With Renal Dysfunction
Preoperative Laboratory Evaluation
Perioperative Dialysis
Medications
Intraoperative Management
Strategies for Renal Protection
Vascular Access
Environment
Fluids and Blood Products

Anesthetic Agents

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Postoperative Concerns
THE ANESTHESIA PRACTITIONER IS OFTEN FACED with a child
who has acute kidney injury (AKI) or renal failure. Renal disease requires
the practitioner to be vigilant about fluid homeostasis, acid-base balance,
electrolyte management, choice of anesthetics, and potential
complications. This requires a thorough understanding of the excretory
and fluid homeostatic functions of the kidney, particularly in the neonate
and younger child. If not managed assiduously, perioperative renal
dysfunction can deteriorate into renal failure or multiorgan system
failure resulting in significant morbidity or mortality. The anesthesia
provider must understand renal physiology, appropriate preoperative
preparation, intraoperative management, and postoperative care of the
child with renal disease.

Renal Physiology
The basic functions of the kidney are to maintain fluid and electrolyte
homeostasis and metabolism. The first step in this tightly controlled
process is the production of the glomerular filtrate from the renal plasma.
The glomerular filtration rate (GFR) depends on renal blood flow (RBF),
which depends on the systolic blood pressure and circulating blood
volume. The kidneys are the best perfused organs per gram of weight in
the body. They receive 20% to 30% of the cardiac output maintained over
a wide range of blood pressures through changes in renal vascular
resistance. Numerous hormones play a role in this autoregulation,
including vasodilators (i.e., prostaglandins E and I2, dopamine, and nitric

oxide) and vasoconstrictors (i.e., angiotensin II, thromboxane, adrenergic
stimulation, and endothelin). Congestive heart failure and volume
contraction severely limit the ability of the kidney to maintain
autoregulation.
When adjusted for body surface area (BSA) or scaled using allometric
theory (see Chapter 7), both RBF and GFR double in the first 2 weeks of
postnatal life and both continue to increase steadily, reaching adult
values by 2 years of age (see Figs. 7.11 and 7.12).1,2 The increases in RBF
over time parallel similar increases in cardiac output and decreases in
renal vascular resistance. The initial GFR and the rate of increase during
the first few years correlate with the neonate's postmenstrual age at birth.

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For example, the GFR (corrected using BSA or allometry) of a neonate
born at 28 weeks gestation is one-half of that of a full-term infant (see
Figs. 7.11 and 7.12).3 GFR may be estimated from the serum creatinine
concentration and the height of the child according to the following
formula4,5:
In the equation, k is a constant that varies with age; 0.413 for infants,
0.55 for children, and 0.7 for adolescent boys. The serum creatinine
concentration, especially in the first days of life, reflects the maternal
serum creatinine concentration and therefore cannot be used to predict
neonatal renal function until at least 2 days after birth.6

Fluids and Electrolytes
The kidney regulates the total body sodium balance and maintains
normal extracellular and circulating volumes.7 The adult kidney filters
25,000 mEq of sodium per day, but it excretes less than 1% through

extremely efficient resorption mechanisms along the nephron. The
proximal tubule resorbs 50% to 70%, the ascending limb of the loop of
Henle resorbs about 25%, and the distal nephron accounts for 10% of the
filtered sodium load. Several hormones, including renin, angiotensin II,
aldosterone, and atrial natriuretic peptide (ANP), and changes in
circulating blood volume contribute to maintaining the sodium balance.8
Serum osmolality is tightly regulated through changes in arginine
vasopressin (AVP) release and thirst.9–11 AVP, also called antidiuretic
hormone, is synthesized in the hypothalamus and stored in the posterior
pituitary, where it is released in response to an increasing plasma
osmolality. AVP is also released in response to decreases in the
circulating blood volume and hypotension, including responses to
nausea, vomiting, opioids, inflammation, and surgery. AVP binds to
receptors in the collecting duct, increasing the permeability of the tubules
to water and leading to increased water resorption and concentrated
urine. Neonates are much less able to conserve or excrete water
compared with older children, rendering the fluid management and
volume issues important tasks for the anesthesiologist in this young age
group.12
The regulation of serum potassium is managed by the kidney and

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depends on the concentration of plasma aldosterone. Aldosterone binds
to receptors on cells in the distal nephron, increasing the secretion of
potassium in the urine. Neonates are much less efficient at excreting
potassium loads compared with adults, and the normal range of serum
potassium concentrations is therefore greater in neonates; Table 28.1
provides the normal values.13 Potassium regulation is affected by the

acid-base status; excretion of potassium increases in the presence of
alkalosis and decreases in the presence of acidosis. Causes of
hyperkalemia and hypokalemia are presented in Tables 28.2 and 28.3,
respectively.
TABLE 28.1
Normal Values of Serum Potassium

Age

Serum Potassium Range (mEq/L)

0–1 month
1 month–2 years
2–17 years
>18 years

4.0–6.0
4.0–5.5
3.8–5.0
3.2–4.8

TABLE 28.2
Causes of Hyperkalemia

Transcellular Shifts
Acidosis

β-Adrenergic blockers

Insulin deficiency

Burns

Tumor lysis syndrome

Rhabdomyolysis

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Succinylcholine

Decreased Excretion
Renal failure

Potassium-sparing diuretics

Cyclosporine

Nonsteroidal antiinflammatory drugs

Angiotensin-converting enzyme inhibitors

Mineralocorticoid deficiency

Adrenal insufficiency

Congenital adrenal hyperplasia

Hyporeninemic hypoaldosteronism

Primary mineralocorticoid deficiency

Mineralocorticoid resistance

Prematurity

Obstructive uropathy

Pseudohypoaldosteronism

Increased Intake
Potassium supplements, oral or intravenous

Blood transfusions

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Potassium-containing antibiotics

TABLE 28.3
Causes of Hypokalemia

Transcellular Shift
Insulin

β-Adrenergic agonists

Increased Excretion

Vomiting

Diarrhea

Nasogastric suction

Laxatives

Diuretics

Cisplatin

Amphotericin B

Renal tubular acidosis

Bartter syndrome

Corticosteroids

Decreased Intake
Malnutrition

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Anorexia nervosa

Acid-Base Balance
The kidney is involved in the regulation of acid-base balance and the

response to the stress of illness. The kidney reclaims virtually all of the
filtered bicarbonate in the proximal tubule and regenerates bicarbonate
(HCO3−) lost in the neutralization of acid generated by the normal
combustion of food, especially protein, and the formation of bone. New
bicarbonate is the product of cells in the distal nephron that decompose
the carbonic acid (H2CO3) formed from water (H2O) and carbon dioxide
(CO2) by carbonic anhydrase. The protons (H+) that are generated from
this process are pumped into the lumen of the collecting duct, where they
combine with hydrogen phosphate (HPO42−) or ammonia (NH3)
generated by the catabolism of amino acids, mainly glutamine, in the
tubule cells.
Infants, especially neonates, maintain a slightly acidotic blood (pH =
7.37) and decreased plasma bicarbonate concentration (22 mEq/L)
compared with older children and adults (pH = 7.39; plasma bicarbonate
= 24 to 28 mEq/L).14 The reduced plasma concentration of HCO3− is the
result of a reduced threshold or the plasma concentration at which
HCO3− is incompletely resorbed by the kidney. Neonates maintain acidbase homeostasis but are limited in their ability to respond to an acid
load.15 This is especially true for preterm infants.

Disease States
The causes of and differences in renal diseases between children and
adults are substantive. Depending on the cause of the renal disease,
management may be different. Adult renal disease usually results from
long-standing diabetes mellitus or hypertension with an associated
compromise in cardiovascular function. Children may also have renal
failure owing to diseases such as sickle cell disease or systemic lupus
erythematosus, but cardiovascular function is far less commonly
compromised.

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Acute Renal Failure and Acute Kidney Injury
Acute renal failure (ARF) or acute renal insufficiency is defined as an
abrupt deterioration in the ability of the kidneys to clear nitrogenous
wastes, such as urea and creatinine. Concomitantly, there is a loss of
ability to excrete other solutes and maintain a normal water balance. This
leads to the clinical presentation of acute renal insufficiency: edema,
hypertension, hyperkalemia, and uremia.
Acute kidney injury (AKI) has almost replaced the traditional term acute
renal failure (ARF), which was used in reference to the subset of patients
who had an acute need for dialysis. With the recognition that even
modest increases in serum creatinine are associated with a dramatic
increase in mortality, the clinical spectrum of acute decline in GFR is
broader. Minor deterioration in GFR and kidney injury are captured in a
working clinical definition of kidney damage that allows early detection
and intervention and uses AKI in place of ARF. The term ARF is
preferably restricted to those with AKI who also require renal
replacement therapy.16 The prognosis of AKI is assessed in part by the
use of the RIFLE criteria, which include three severity categories (i.e.,
Risk, Injury, and Failure) and two clinical outcome categories (Loss and
End-stage renal disease) (Table 28.4).
TABLE 28.4
RIFLE Classification of Renal Failure and Kidney Injury
RIFLE
Factors

GFR Criteria

Urine Output Criteria

Risk

Increased Cr × 1.5 or decreased GFR >25%

Injury

Increased Cr × 2 or GFR decrease >50%

UOP <0.5 mL/kg per hour > 6
hours
UOP <0.5 mL/kg per hour > 12
hours

Failure

Increased Cr × 3 or GFR decrease of 75%
or Cr ≥4 mg/dL

UOP <0.3 mL/kg per hour >
24 hours or

Acute rise ≥0.5 mg/dL

Anuria > 12 hours

Loss

Persistent ARF: complete loss of kidney function > 4 weeks

ESKD

End-stage kidney disease (> 3 months)

High
sensitivity

High
specificity

ARF, acute renal failure; Cr, creatinine; ESKD, end-stage kidney disease; GFR,
glomerular filtration rate; RIFLE, Risk of renal dysfunction, Injury to the kidney,

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Failure of kidney function, Loss of kidney function, and End-stage kidney disease;
UOP, urine output.
Modified from Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute
Dialysis Quality Initiative Workgroup. Acute renal failure—definition, outcome
measures, animal models, fluid therapy and information technology needs: the
Second International Consensus Conference of the Acute Dialysis Quality
Initiative (ADQI) Group. Crit Care. 2004;8:R204–R212.

The term ARF has often been incorrectly used interchangeably with
acute tubular necrosis (ATN), which usually refers to a rapid deterioration
in renal function occurring minutes to days after an ischemic or
nephrotoxic event. Although acute tubular necrosis is an important cause
of ARF, it is not the sole cause, and the terms are not synonymous. For
the purposes of this chapter, AKI refers to the disease formerly called

ARF.

Etiology and Pathophysiology
AKI is often multifactorial in origin or the result of several distinct
insults. To treat AKI, it is important to understand its causes and
pathophysiology. The etiologies of AKI are varied, but can be broadly
classified as follows (Table 28.5):
TABLE 28.5
Causes of Acute Renal Failure
Prerenal Failure

Renal Failure

Postrenal Failure

Hypovolemia

Acute glomerulonephritis

Obstruction

Volume loss

Postinfectious

Gastrointestinal, renal losses

Membranoproliferative
glomerulonephritis

Sequestration (burns,
postoperative)

Rapidly progressive
glomerulonephritis
Glomerulonephritis due
to systemic disease (e.g.,
HUS, DIC, SLE)

Hypotension
Shock
Vasodilators

Acute interstitial nephritis
Drug-induced
hypersensitivity
(penicillin)
Infections

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Intrinsic (papillary necrosis due to
diabetes, sickle cell disease, or
analgesic nephropathy)
Intrarenal abnormalities, ureteral
obstruction, obstruction of the
bladder or urethra
Extrinsic (tumor compression,
lymphadenopathy)

Decreased effective blood flow Tubular disease
Low cardiac output
Cirrhosis
Nephrotic syndrome
Renal hypoperfusion

ATN (ischemic,
nephrotoxic)
Intratubular obstruction
(uric acid, oxalate)
Cortical necrosis

Use of ACE inhibitors

Gram-negative sepsis

NSAIDs

Hemorrhage

Hepatorenal syndrome

Shock

Vascular occlusion

Acute renal failure

Thromboembolic

phenomenon

Toxins

Aortic dissection

Heavy metals

Renal vein thrombosis
(dehydration,
hypercoagulable state,
neoplasm)

Insecticides

Organic solvents

Hemoglobin
Myoglobin
Chronic renal failure
Chronic interstitial
nephritis
Chronic
glomerulonephritis
Chronic
glomerulosclerosis
Nephrocalcinosis
Obstructive uropathy
Hypertension

ACE, angiotensin-converting enzyme; ATN, acute tubular necrosis; DIC,
disseminated intravascular coagulation; HUS, hemolytic uremic syndrome;
NSAIDs, nonsteroidal antiinflammatory drugs; SLE, systemic lupus
erythematosus.

■ Prerenal, implying poor renal perfusion as the cause
■ Renal, implying intrinsic renal disease or damage as
the cause
■ Postrenal, implying an obstruction to the excretion of
urine as the cause
Prerenal insults comprise the majority (up to 70%) of cases of AKI.
They usually result from massive losses of extracellular fluid, such as in
gastroenteritis, burns, hemorrhage, or excessive diuresis, as well as in

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cardiac failure and sepsis. The common feature of this condition is
diminished renal perfusion. In response to the reduction in RBF, there is
a compensatory increase in afferent tone, which decreases the GFR and
increases the retention of salt and water. The net effect of these events is a
drastic reduction in urine volume, often leading to oliguria and/or
anuria. If the underlying problem is recognized early and treated
aggressively, progressive renal insufficiency may be averted.
Nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme
(ACE) inhibitors, and angiotensin receptor blockers can aggravate
prerenal azotemia by further reducing glomerular capillary pressure and
the GFR.17
Parenchymal disease or injury accounts for 20% to 30% of the cases of
abrupt onset of AKI. In infants, the common causes include birth

asphyxia, sepsis, and cardiac surgery. In older children, the important
causes of AKI include trauma, sepsis, and hemolytic uremic syndrome.
Prolonged prerenal azotemia may result in overt renal injury. Similarly,
intrarenal obstruction to blood flow from thrombi or vasculitis may cause
renal failure. Drugs such as aminoglycosides or amphotericin B or other
nephrotoxins, including radiocontrast agents, may induce AKI through
tubular or interstitial injury as a result of allergic reactions, as can be seen
with penicillins. Acute glomerulonephritis is another cause of AKI in
children; rarely, pyelonephritis can lead to AKI.
The remaining causes of AKI result from the obstruction to urine flow.
These conditions account for less than 10% of all cases of AKI and may
involve obstruction of both kidneys. Sudden anuria suggests a postrenal
cause for the AKI. The obstruction can occur within the collecting system
of the kidney (intrarenal), in the ureter, or in the urethra (extrarenal).
Intrarenal obstruction may occur with the tumor lysis syndrome with the
deposition of uric acid crystals, from myoglobinuria, hemoglobinuria, or
from medications such as acyclovir and cidofovir. Extrarenal obstruction
can be caused by stones inspissated in the ureters or from external
compression by lymph nodes or a tumor. As with other forms of AKI,
prompt recognition and appropriate intervention to relieve the
obstruction may facilitate full recovery of renal function and obviate a
permanent reduction in renal function.
The exact pathophysiology of AKI remains unclear, but several factors
have been identified.18 In the initial phase of AKI, profound renovascular

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vasoconstriction reduces GFR (Fig. 28.1). Factors known to increase renal
vasoconstriction include increased activity of the renin-angiotensin and

the adrenergic systems and endothelial dysfunction with increased
endothelin release and decreased nitric oxide synthesis. However,
therapeutic interventions to vasodilate the intrarenal vasculature, such as
prostaglandin and dopamine infusions, ACE inhibitors, calcium channel
blockers, and endothelin receptor antagonists, have not significantly
reversed established AKI.19

FIGURE 28.1 Hemodynamic factors in the pathogenesis

of acute renal failure.
Another factor in the pathogenesis of AKI is renal tubule cell injury,
the direct result of a nephrotoxic agent or from an ischemic insult (Fig.
28.2). Cellular injury leads to sloughing of the brush border, swelling,
mitochondrial condensation, disruption of cellular architecture, and loss
of adhesion to the basement membrane with shedding of cells into the
tubular lumen.20 These changes, which occur within minutes of an
ischemic event, contribute to the decreased GFR by obstructing the
lumen of the tubule.21 These cellular changes allow the filtrate to leak
back into the peritubular blood, reducing the excretion of solutes and the

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effective GFR.

FIGURE 28.2 Influences of specific injuries on the

nephron in the pathogenesis of acute renal failure. ATP,
adenosine triphosphate.
Some of the cellular derangements in AKI, such as a reduction in ATP

concentrations,21 cell membrane injury by reactive oxygen molecules,22
and increased intracellular calcium concentrations from changes in
membrane phospholipid metabolism, lead to cell death. Reactive oxygen
molecules also stimulate the production of cytokines and chemokines
that play a role in cell injury and vasoconstriction.
Neutrophils that are recruited during reperfusion injury after renal
ischemia mediate parenchymal renal damage.23 Reperfusion injury
increases intracellular adhesion molecule 1 (ICAM-1) on endothelial cells
promoting the adhesion of circulating neutrophils and their eventual
infiltration into the parenchyma. Neutrophils then release reactive
oxygen molecules, elastases, proteases, and other enzymes that lead to
further tissue injury.

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Diagnostic Procedures
A thorough history and physical examination can yield important insight
into the likely causes of AKI. The initial laboratory assessment of a child
with AKI should include the measurement of serum urea, creatinine,
electrolytes, and a urinalysis. Prerenal azotemia is typically associated
with a ratio of blood urea nitrogen (BUN) to creatinine that exceeds 20. In
cases of renal parenchymal dysfunction, this ratio is closer to 10.
Hematuria and proteinuria are consistently present in AKI, independent
of the cause, although the presence of cellular casts, especially red blood
cell casts, in the urinary sediment is suggestive of glomerulonephritis.
Granular casts are associated with prerenal azotemia.
One test to distinguish prerenal azotemia from established renal failure
from ischemia or nephrotoxins is the fractional excretion of sodium
(FENa). The FENa is calculated using the following equation:

UNa and SNa are urine and serum sodium concentrations, and UCr and
SCr are the urine and serum creatinine concentrations, respectively. In
prerenal azotemia, the FENa is usually less than 1% for adults and
children and less than 2.5% for infants. In established AKI from ischemia
and nephrotoxins, but not acute glomerulonephritis, the FENa usually
exceeds 1%. Administration of diuretics may confound the interpretation
of this test.
The initial radiologic assessment of children with AKI is
ultrasonography. Renal ultrasound does not depend on renal function
and can define the renal anatomy, changes in parenchymal density, and
possible outlet obstruction by demonstrating dilation of the urinary tract.
Doppler interrogation of the renal vessels provides information on
vascular flow. Further radiographic studies, such as voiding
cystourethrography, nuclear renal flow scanning, dynamic functional
MRI, and abdominal computed tomography (CT), may be indicated in
select children and conditions.

Therapeutic Interventions
Therapeutic interventions in children with AKI should be aimed at the

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underlying cause and at improving renal function and urine flow.
Children with AKI caused by hypovolemia should be fluid resuscitated
with at least 20 mL/kg over 30 to 60 minutes with normal saline solution
or a balanced salt solution. For children with significant hypotension, an
alternative choice is a colloid-containing solution. Children with oliguria
caused by hypovolemia usually respond within 4 to 6 hours with

increased urine output. Anecdotal reports have supported the use of lowdose dopamine in AKI. A recent clinical trial has demonstrated benefit
from dopamine in improving urine output in very low–birth-weight
neonates.24
Diuretics have been commonly used to treat oliguric AKI. There are
several theoretical reasons why mannitol, furosemide, and other loop
diuretics may ameliorate AKI. First, diuretics may convert oliguric AKI
to nonoliguric AKI. Second, loop diuretics decrease energy-driven
transport in the loop of Henle, and this may protect cells in regions of
hypoperfusion. However, neither mannitol nor loop diuretics can
predictably convert an oliguric patient with AKI to a polyuric patient.
Diuretics have not been shown in clinical studies to influence renal
recovery, need for dialysis, or survival in patients with AKI.25,26 Diuretics
should be used only after the circulating volume has been adequately
restored and should be stopped if there is no early response.
Dopamine has been widely used to prevent and manage AKI. In low
doses (0.5–2.0 µg/kg per minute), dopamine increases renal plasma flow,
GFR, and renal sodium excretion by activating dopaminergic receptors.
Infusion rates in excess of 3 µg/kg per minute stimulate α-adrenergic
receptors on systemic arterial resistance vasculature, causing
vasoconstriction; cardiac β1-adrenergic receptors, increasing cardiac
contractility, heart rate, and cardiac index; and β2-adrenergic receptors
on systemic arterial resistance vasculature, causing vasodilatation. In a
meta-analysis of 24 studies and 854 adult patients, dopamine did not
prevent renal failure, alter the need for dialysis, or change the mortality
rate. In a randomized clinical trial of low-dose dopamine in 328 critically
ill adult patients, dopamine did not change the duration or severity of
the renal failure, need for dialysis, or mortality.27 From these data, the
routine use of low-dose dopamine in patients with AKI cannot be
supported.
Several other agents that were useful in experimental models of AKI

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have been investigated but have not shown clinical success. ANP
increases GFR in animal models of AKI by increasing renal perfusion
pressure and sodium excretion. An initial study demonstrated some
benefit with ANP in patients with AKI,28 especially in those with oliguric
AKI,29 although a subsequent study of 222 adult patients with oliguric
AKI failed to detect a difference between patients treated with ANP and
placebo in terms of the need for dialysis or mortality.30 Insulin-like
growth factor 1 has been beneficial in animal models of AKI, presumably
by potentiating cell regeneration. However, in a multicenter, placebocontrolled trial in adult patients with AKI, insulin-like growth factor 1
failed to speed the recovery, decrease the need for dialysis, or alter
mortality.31 Thyroxine abbreviates the course of experimental AKI but
had no effect on the duration of renal failure and actually increased
mortality threefold (by suppression of thyroid-stimulating hormone).32
In patients with severe AKI, renal replacement therapy through
dialysis is life sustaining. The indications for initiation of dialytic therapy
are persistent hyperkalemia, volume overload refractory to diuretics,
severe metabolic acidosis, and overt signs and symptoms of uremia such
as pericarditis and encephalopathy. Many nephrologists recommend
dialysis if the BUN value approaches 100 mg/dL or even earlier,
especially in the oliguric patient, although this has not proved to alter
outcome. A retrospective study that compared early (BUN <60 mg/dL)
versus late (BUN >60 mg/dL) initiation of dialysis in adult patients
suggested that early initiation improved survival.33 However, the timing
of the initiation of dialysis remains an unresolved question.
Three strategies are available to replace renal function in critically ill
children and adults: hemodialysis, peritoneal dialysis, and a variation of

continuous replacement therapies, such as continuous venovenous
hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD),
and continuous venovenous hemodiafiltration (CVVHDF). None of these
strategies has been proven superior to the others. However, in the
individual child, one strategy may be more practical than the others.
Hemodialysis is technically more difficult than peritoneal dialysis in an
infant and hemodynamically unstable children. Continuous replacement
therapies appear to cause less hemodynamic instability compared with
hemodialysis and offer more predictable solute and fluid removal than
peritoneal dialysis. Hemodialysis and continuous replacement therapies
require large-bore vascular access to achieve the large blood flows that

2919


are necessary to support these strategies.
Although these three strategies differ technically, they share similar
principles (Fig. 28.3). All three strategies remove nitrogenous wastes (i.e.,
urea), excess fluid, and excess solutes, especially potassium. This is
achieved by circulating the child's blood over a semipermeable
membrane that separates the blood from a salt solution (i.e., dialysate) on
the contralateral surface. The movement of solutes across the membranes
occurs by diffusion (i.e., solutes move across the membrane along their
concentration gradients) and ultrafiltration (i.e., osmotic or hydrostatic
pressures). The rate of removal of water and solute waste depends on the
characteristics of the membrane (i.e., pore size and selectivity), diffusion,
and ultrafiltration.34

FIGURE 28.3 Principles of dialysis. Solute (pink circles)

moves from the blood to the dialysate (broken arrows) in
response to a concentration gradient (i.e., diffusion). The
obligate passive movement of water (blue circles)
attempts to maintain appropriate osmolarity. This flux of
solute and water (i.e., ultrafiltration) may be enhanced by
increased osmotic pressure (i.e., glucose in peritoneal
dialysis fluid) or by increased hydrostatic pressure, which
is created mechanically as transmembrane pressure in
hemodialysis.
The permeability characteristics and surface areas for the membranes
are known for specific dialyzers used in hemodialysis and hemofiltration.
The peritoneum serves as the dialysis membrane in peritoneal dialysis
and remains physically unalterable, but changes in dialysate composition

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and length of time the dialysate is exposed to the peritoneal membrane
changes the amount of solute and water removed. In all forms of renal
replacement therapy, the therapeutic prescription is individualized for
the child.

Hemodialysis
Hemodialysis is very effective for AKI, being the best modality for the
rapid removal of toxins, such as drug overdoses or other ingestions or
metabolic toxins resulting from poisoning or inborn errors. Hemodialysis
is very efficient, reducing the BUN by 60% to 70%, normalizing the
serum potassium concentration, and removing fluid equal to 5% to 10%
of the body weight within 3 to 4 hours. To accomplish this, large-vessel
venous access is required to provide rapid blood flows (5-10 mL/kg per

minute). In infants, this is achieved by inserting a double-lumen catheter
into the subclavian, internal jugular, or femoral vein. In small infants,
two single-lumen catheters placed in different sites may be necessary to
access and return the blood. Rarely, a single-lumen catheter may be used
for both outflow and return of blood. Modern hemodialysis machines
have microprocessors that can accurately measure the amount of fluid
removed and this should be summarized for the anesthesiologist.
Hemodialysis usually requires systemic anticoagulation with heparin,
the effectiveness of which can be monitored by the activated clotting time
(ACT). Hemodialysis can be undertaken without an anticoagulant in
children who are at significant risk for bleeding by using a rapid blood
flow rate and by frequently rinsing the blood circuit with saline.
However, clotting commonly forms within the circuit with subsequent
loss of the extracorporeal blood.
In addition to the risk of bleeding, hemodialysis is associated with
several other adverse effects, the most common of which is hypotension.
This usually results from overly aggressive removal of fluid, although it
can also result from sepsis or the release of cytokines and autokines from
blood passing over the surface of the hemodialysis filter. Muscle cramps,
headache, nausea, and vomiting are also commonly reported. A more
serious complication of hemodialysis is the disequilibrium syndrome that
is related to the rapid removal of solute from the bloodstream with slow
equilibration with the tissues, particularly the brain. This can cause
cerebral edema, manifested by headache, obtundation, seizures, or coma.

2921


The disequilibrium syndrome is usually reported in children undergoing
dialysis for the first time. This can be obviated by dialyzing for brief but

frequent sessions initially, especially if the BUN concentration is
increased substantially. Infection of the dialysis catheter is another
common problem that can be minimized by using sterile central line
techniques.

Peritoneal Dialysis
Peritoneal dialysis has a long history as renal replacement therapy in
children.35 It is relatively simple and easy to perform, even in small
infants, and there is usually no hemodynamic instability. Although not as
efficient as hemodialysis, optimal results are obtained if it is performed
continuously to control solute and water balance. Peritoneal dialysis
involves instilling dialysate fluid into the peritoneum for a set period and
then draining the fluid and replacing it with fresh dialysate. This cycling
removes waste products by diffusion and water by ultrafiltration as a
consequence of a high glucose concentration in the dialysate. The efficacy
of peritoneal dialysis depends on the volume of dialysate instilled per
cycle and the number of cycles per day. Most children with acute renal
failure are managed with 1- to 2-hour cycles of 5- to 30-mL/kg dwell
volumes. Children with chronic renal failure are managed with greater
cycle times and larger dwell volumes. The amount of fluid removed can
be controlled by changing the concentration of the glucose in the
dialysate. Short-term peritoneal dialysis can be accomplished with a
nontunneled catheter, but should dialysis be required beyond 3 to 5 days,
a subcutaneously tunneled cuffed catheter is preferred to minimize the
risk of peritonitis.
The principal complications of peritoneal dialysis are infection and
mechanical problems related to the catheter. It is common to find poor
drainage from the catheter, usually the result of fibrin occlusion of the
catheter or from omentum or bowel covering the inlet holes. The catheter
may leak at its point of insertion. Hernias, especially inguinal hernias in

boys, may develop as a consequence of the increased abdominal pressure
from the infused dialysate. Mild hyponatremia may develop in infants
because of the relatively low sodium concentration (130 mEq/L) in
commercial dialysate. Less common but serious complications include
bowel injury and intraabdominal hemorrhage from catheter insertion

2922


and peritonitis.

Chronic Renal Failure
The loss of functioning renal mass results in a compensatory increase in
filtration by the remaining renal tissue.36 For example, within the first 48
hours after a unilateral nephrectomy, there is a demonstrable increase in
the GFR and evidence of contralateral renal hypertrophy. By 2 to 4
weeks, the GFR has returned to 80% of normal, and there is no clinical
evidence of renal dysfunction. With the loss of 50% to 75% of renal mass,
there is an increase in the residual function to 50% to 80% of normal and
often little evidence of clinical renal insufficiency. When the residual
renal function decreases to 30% to 50% of normal, the term chronic renal
insufficiency applies. At this point, acute illness and other stress states
may result in acidosis, hyperkalemia, and dehydration. It is only when
the residual function decreases to less than 30% of normal that the term
chronic renal failure is used. At this point, electrolyte abnormalities begin
to appear, and more importantly, there is limited ability of the kidney to
adjust to perturbations in volume status and electrolyte concentrations.
The term uremia refers to the symptoms of anorexia, nausea, lethargy,
and somnolence that develop as a result of chronic renal failure. Uremia
ultimately leads to death unless dialysis therapy or renal transplantation

is performed. Initiating dialysis or transplanting a kidney is referred to as
end-stage renal disease care.
Chronic renal insufficiency and chronic renal failure are both
categories within the larger schema of chronic kidney disease (CKD).
Although the stages are defined by categorizing continuous measures of
function (i.e., GFR) and therefore are somewhat arbitrary, they do
provide a context for the evaluation and management of kidney disease.
There are six stages of CKD:
Stage I: The GFR is normal (>90 mL/minute per 1.73 m2), but there
may be evidence of chronic renal disease, including an abnormal
urinalysis, hypertension, or abnormal renal ultrasound.
Stage II: A GFR of 60 to 89 mL/minute per 1.73 m2 indicates mild
kidney damage and mild decrease in GFR.
Stage III: A GFR of 30 to 59 mL/minute per 1.73 m2 is a moderate
decrease in the GFR.

2923


Stage IV: A GFR of 15 to 29 mL/minute per 1.73 m2 is a severe
decrease in the GFR, often accompanied by electrolyte or metabolic
derangements.
Stage V: A GFR <15 mL/minute per 1.73 m2 indicates kidney failure
that requires renal replacement therapy.
Stage VI: Patients are undergoing dialysis or are transplant recipients.
Despite losses of up to 90% of renal function, sodium homeostasis
usually is well maintained in chronic renal failure. With large decreases
in the GFR, the kidney maintains normal serum sodium by increasing the
FENa from less than 1% up to 25% to 30%, largely through decreases in
distal tubular resorption. Some of the hormonal factors associated with

this adaptation include aldosterone, ANP, and a poorly characterized
natriuretic hormone that inhibits Na+/K+-ATPase. With chronic renal
failure, the kidney loses its ability to handle a wide range of sodium
intake, from 1 to 250 mEq/m2 per day. Instead, the kidney may only be
able to handle a narrow range of sodium intake of 50 to 100 mEq/m2 per
day. It may be possible to decrease this obligatory excretion of sodium to
5 to 20 mEq/m2 per day, although it may occur only after weeks of
decreasing the sodium intake slowly. Certain children with renal disease,
especially those with obstructive uropathy or tubulointerstitial disease,
may be unable to adjust to a decreased sodium intake and display a saltlosing nephropathy. These children are prone to dehydration with salt
restriction and may need supplemental salt to ensure normal growth. In
others, a regular diet may lead to sodium retention, volume overload,
and hypertension; sodium intake must be individualized to fit the
limitations of each child.
Water balance is also affected by chronic renal failure. There is an
obligatory total osmolar excretion that limits the ability of the kidney to
excrete free water. The concentrating ability of the kidney is affected,
limiting its ability to make a maximally concentrated or dilute urine.
These limitations may result in water retention and hyponatremia or
dehydration if water is administered in amounts exceeding the kidney's
capabilities. These limitations must be considered when treating children
with chronic renal failure, particularly before surgery when free access to
water is restricted.
In those with chronic renal failure, the serum potassium concentrations
usually remain normal until the GFR is less than 10% of normal.

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Potassium excretion normally occurs in the distal nephron. However, in

response to an increase in potassium intake or loss of renal mass, Na+/K+ATPase increases in the remaining collecting tubules; this is responsible,
in part, for the augmented excretion of potassium per nephron. In uremic
animals, potassium is excreted from the renal tubules sixfold faster than
in nonuremic animals and 1.5 times the filtered potassium load. Partial
adaptation can occur in the absence of aldosterone, but aldosterone plays
an important role in the maintenance of normal potassium homeostasis.
This is demonstrated by the presence of hyperkalemia in children with
hyporeninemic hypoaldosteronism or in those treated with the
aldosterone antagonist spironolactone.
Approximately 13% of dietary potassium is excreted via the colon. This
can increase to 50% by the activation of colonic Na+/K+-ATPase via
aldosterone. An additional mechanism that plays an essential role in the
adaptation to an acute potassium load is the redistribution of potassium
from the extracellular to the intracellular compartment, which depends
on insulin, β-adrenergic catecholamines, aldosterone, and pH. Despite
the presence of total body potassium depletion in uremia, the uptake of
potassium into the cells is impaired. This contributes to the intolerance to
an acute potassium load in uremia despite the ability to excrete a
potassium load.
Hyperkalemia is a major problem in chronic renal failure.37
Hyperkalemia can result from an extrinsic potassium load, but it may
also be caused by fasting or acidosis, in which case the source of the
potassium is the intracellular compartment. This can be a particular
problem when a child has fasted before surgery and can be ameliorated
by an infusion of glucose and insulin. Drugs that can cause hyperkalemia
in renal failure include spironolactone, β-adrenergic blockers, and ACE
inhibitors. When clinically significant hyperkalemia develops in a child
with chronic renal failure, the first-line therapy is to stabilize the
myocardium with exogenous calcium and then to redistribute the
potassium into the intracellular compartment with insulin and glucose.

To deliver the same dose of ionized calcium, the dose of calcium
gluconate (in milligrams per kilogram) should be three times that of
calcium chloride. All doses of calcium are optimally delivered through a
central venous access line because calcium infusions are irritating to
peripheral veins and can cause necrosis of the skin if extravasation
occurs. More definitive correction of hyperkalemia is accomplished by

2925


removing potassium from the body using dialysis or sodium polystyrene
sulfonate (Kayexalate). At eight times the usual asthma dose, nebulized
albuterol has been effective in redistributing potassium intracellularly,
whereas sodium bicarbonate (NaHCO3) administration has not been
effective (Table 28.6). In contrast, significant hypokalemia is unusual in
the absence of potassium restriction, alkalosis, or diuretic therapy.
TABLE 28.6
Treatment of Hyperkalemia
Treatment
Stabilization of Myocardium
Calcium and bicarbonate

Dosage

Calcium gluconate: 10% 30–100 mg/kg IV or
Calcium chloride: 10% 10–33 mg/kg IV
Sodium bicarbonate: 1 mEq/kg IV if acidotic

Shifting of Potassium to Intracellular Space
Hyperventilation

Insulin and glucose

Insulin: 0.10–0.3 unit/kg or
0.1 U/kg per hour infusion
Glucose: D50 1–2 mL/kg or
D25 2–4 mL/kg IV or
D5 1–2 mL/kg per hour

Albuterol
Decreasing Total Body Potassium
Sodium polystyrene sulfonate (Kayexalate)
Furosemide (diuretic)

Albuterol: 2.5–5 mg/mL nebulization
1 g/kg up to 40 g every 4 hours PO or PR
0.5 mg/kg up to 40 mg

D, dextrose; IV, intravenous; PO, per os (oral); PR, per rectum (suppository).

Metabolic acidosis is common in those with chronic renal failure.38 In
moderate renal insufficiency, the type of metabolic acidosis is a non–
anion gap acidosis, but in severe renal insufficiency, the metabolic
acidosis is an anion gap acidosis, because of the presence of excess
phosphate, sulfate, and organic acids. The primary cause of metabolic
acidosis in chronic renal failure is the inability of the remaining proximal
renal tubules to increase ammonium formation to keep pace with the loss
of renal mass. The kidney becomes unable to generate the 1 to 3 mEq/kg
per day of new bicarbonate that is necessary to compensate for the
bicarbonate lost to buffering endogenous acids. Previous studies have
suggested a major role for decreased resorption of bicarbonate by the

proximal renal tubule in chronic renal failure. Although this may occur

2926


in
the
presence
of
volume
overload,
severe
secondary
hyperparathyroidism, and disorders such as Fanconi syndrome, it is not
a major cause of acidosis in chronic renal failure. Except for severe
phosphate depletion, decreased excretion of phosphate as a titratable
acid normally does not contribute to metabolic acidosis.
One of the earliest manifestations of chronic renal failure is secondary
hyperparathyroidism.39 Secondary hyperparathyroidism, which results
from inadequate formation of 1,25-(OH)2 vitamin D (i.e., 1,25dihydroxyvitamin D3 or calcitriol), develops in moderate renal
insufficiency in the presence of normal serum concentrations of calcium
and phosphorus. As the renal insufficiency becomes more severe, overt
hypocalcemia and hyperphosphatemia often develop. Hypocalcemia is
caused by decreased calcium absorption from the gastrointestinal tract as
a result of a true deficiency of 1,25-(OH)2 vitamin D. Diminished release
of calcium from bone occurs as a result of resistance to the action of
parathyroid hormone. Calcium and phosphate may be deposited in soft
tissues as a consequence of hyperphosphatemia.
The kidney plays a key role in the maintenance of phosphate
homeostasis by regulating its excretion. In the presence of a normal GFR,

the kidney excretes 5% to 15% of the filtered load of phosphate, whereas
in chronic renal failure, the kidney can increase its fractional excretion of
phosphate to 60% to 80%. Through this adaptation, the kidneys are able
to maintain a phosphate balance in chronic renal failure, but they do so at
an increased serum phosphate concentration. More importantly, the
failing kidneys have no reserve with which to increase phosphate
excretion in response to a phosphate load. In children with chronic renal
failure, a large phosphate load, such as can occur with the administration
of a phosphate-containing enema, can lead to life-threatening
hyperphosphatemia and hypocalcemia.

Hematologic Problems
One of the most common manifestations of chronic renal failure is
anemia. The anemia of chronic renal failure is the result of impaired
erythropoiesis, hemolysis, and bleeding. Of these, impaired
erythropoiesis is most important and usually the result of a deficiency of
erythropoietin production. Erythropoietin is synthesized and secreted by

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