ACCCN's Critical Care Nursing

478 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

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Support of Renal Function 18





Ian Baldwin
Gavin Leslie




function to deteriorate are not, however, always ischaemic
Learning objectives or necrotic in origin, and a syndrome with degrees of
failure is often evident. Therefore a new consensus defini-
1
After reading this chapter, you should be able to: tion and classification system has been established. This
● summarise the physiology of urine production approach describes staging of ARF severity and embraces
● describe the most likely causes of renal failure in the the concept of acute kidney injury (AKI) where, like other
critically ill adult organs of the body, a dynamic spectrum is found, from
● differentiate between acute and chronic renal failure small indiscrete changes in function that are immediately
● outline treatment approaches in managing renal failure in reversible, through to gross signs and irreversible organ
2
critical illness failure.
● appreciate historical developments in dialysis Acute renal failure is defined by a rapid deterioration in
● describe the indications for renal replacement therapy in renal function (hours to days), which is easily detected
critical care by commonly measured markers of kidney performance,
● understand the principles and challenges associated with including blood urea nitrogen, serum creatinine, and a
nursing management of continuous renal replacement failed ability to adequately regulate electrolytes, sodium
3
therapy in critical care. and water balance. While generally reversible, ARF
can be life-threatening in the critically ill patient if acid–
base balance, electrolyte levels (particularly potassium)
or fluid overloads are not effectively diagnosed and
managed.
The preferred serum marker of renal function is the serum
Key words creatinine level. The exact level of serum creatinine that
is considered excessive is disputed; however, a doubling
urine production of the baseline serum creatinine or levels in excess of 200
acute renal failure µmol/L is commonly agreed on as being indicative of
acute kidney injury ARF. Urine output is also a key factor in determining the
3
continuous renal replacement therapy (CRRT) severity of ARF. It is well established that oliguric renal
dialysis history failure, that is, a urine output of less than 0.5 mL/kg/h in
adults and 1 mL/kg/h in infants, is associated with poorer
patient outcome than the non-oliguric form. 4

Acute renal failure is reported to occur in 20–25% of
intensive care patient admissions, much higher than the
INTRODUCTION broader hospital rate of 5%. 5,6,7 In critical care, ARF often
forms part of the multiple organ dysfunction syndrome,
Sudden deterioration of kidney function, to the point
where there is retention of nitrogenous wastes, or acute whose cause has often been associated with sepsis,
renal failure (ARF), is a common manifestation of critical trauma, pneumonia or cardiovascular dysfunctions (see
illness and is often associated with failure of other organs. Chapter 21). Mortality in intensive care ARF is high, with
Acute renal failure is a syndrome with numerous causes, those patients requiring renal replacement therapy (RRT)
including glomerulonephritis, prerenal azotaemia, having worse outcomes than those patients who can be
8
urinary tract obstruction and vasculitis. Acute tubular managed without this intervention.
necrosis (ATN) is a collective term commonly used to This chapter focuses on the underlying causes and man-
describe acutely deteriorating renal function, reflecting agement of ARF in critical care, with particular emphasis
pathological changes from various renal insults of a on nursing perspectives for managing patients with this
nephrotoxic or ischaemic origin. Factors that cause renal life-threatening organ system failure. 479

480 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

RELATED ANATOMY AND Organs and structures of the urinary system
PHYSIOLOGY

The renal system has a number of functions, including Adrenal
regulation and maintenance of fluid and electrolyte glands
balance, clearance of metabolic and other waste products, Right Kidney
an indirect role in the maintenance of blood pressure, renal
acid–base balance, and an endocrine function. In critical artery
care, an appreciation of the renal system’s fluid manage-
ment, blood pressure, electrolyte and acid–base functions
is essential.
Regulation and maintenance of the extracellular fluid and Right
electrolyte constituents is principally via the process of renal
filtration and reabsorption. The kidneys receive approxi- vein Aorta
mately 25% of the cardiac output each minute, and
excrete approximately 180 L/day of glomerular filtrate. Vena cava Ureter
Fortunately, tubular reabsorption accounts for approxi-
mately 178.5 L/day of the original filtrate, allowing for
a modest daily fluid intake of 1.5 L to achieve fluid
balance. During this process of filtration and reabsorp- Bladder
tion, metabolic byproducts, electrolyte and other wastes
(including many drugs) are also excreted and maintained
in balance. As with all body organ systems, an adequate
blood pressure and supply of oxygen to the kidneys is
paramount in maintaining the fluid and electrolyte
regulatory role.

ANATOMY OF KIDNEYS, NEPHRON AND
URINARY DRAINAGE SYSTEM
The functional anatomy of the renal system includes
the two kidneys, ureters, bladder and urethra (see Figure
18.1). The ureters, bladder and urethra collect, drain A Urethra
and temporarily store the urine produced from each
9
kidney. While important in providing the conduit
for the final excretion of urine, the kidney is the primary Frontal section of kidney
organ of interest in the renal system, particularly in
critical care practice, and hence will be described in Pyramid
more detail from the anatomical and physiological
perspectives. Papilla Fibrous
capsule
The kidneys are located in the retroperitoneal space on Minor
the posterior wall of the abdominal cavity, encased in a calyx
protective combination of the ribs, muscle, fat, tendon Renal
and the renal capsule. Each adult kidney weighs approxi- pelvis Major
mately 140 g. The kidneys may develop a different ana- calyx
tomical appearance, or vary in number and location from Medulla
the classic description provided here. The functional unit Ureter
of the kidney is the nephron, which consists of a filtrate- Cortex
collecting device (the Bowman’s capsule), a convoluted
tubule that varies in length and diameter, finally attach-
ing to a common filtrate-collecting tubule and duct
(see Figure 18.2). Within the Bowman’s capsule rests the B
glomerulus, a tuft of interlaced capillaries that arise from
the afferent arteriole. The efferent arteriole then drains FIGURE 18.1 Kidney and urinary drainage system.
107
from the glomerulus via a closely entwined network
called the peritubular capillaries, until these collect in the
venous network of the kidney.
kidney, which then drain into the renal pelvis where
The glomeruli and nephrons lie in the cortical area of urine is gathered to drain into the ureter. The major
the kidney, while the collecting ducts gather together blood vessels of the kidney, the renal artery and veins
into the renal pyramids, which lie in the medulla of also enter the renal capsule through the pelvis of the
the kidney. The pyramids drain into the calyces of the kidney. 9

Support of Renal Function 481

URINE PRODUCTION, REGULATION OF
GFR AND FILTRATE REABSORPTION
Bowman’s capsule IN THE NEPHRON
Proximal Urine production consists of a three-stage process, which
Glomerulus convoluted occurs in the nephron: glomerular filtration, tubular
tubule reabsorption and tubular secretion (see Figure 18.3). As
Efferent
arteriole previously noted, the production of urine is highly
dependent on delivery of blood under pressure to the
Afferent glomerulus. This results in the first step of the urine pro-
arteriole
duction process, glomerular filtration. The glomerular
filtration rate (GFR) is about 125 mL/min under normal
conditions. Changes in the diameter of the afferent and
Collection efferent arteriole help regulate glomerular blood flow, but
tube this is unable to compensate for large variations of mean
blood pressure; hence, filtration rates may rise or fall
Descending markedly over the course of a day. 10
limb of loop
Interlobular As the filtrate transgresses the glomerulus it is collected
artery Distal into the Bowman’s capsule and delivered into the proxi-
convoluted
tubule mal convoluted tubule, loop of Henle and then the distal
convoluted tubule, where a number of processes result in
Interlobular Ascending the reabsorption of about 99% of the glomerular filtrate.
vein limb of loop The remaining fluid within the tubule drains into the
collecting tubule to form urine. This fluid has substan-
Loop of Henle
tially different properties from the original glomerular
filtrate, as fluid and many electrolytes and glucose are
FIGURE 18.2 Nephron and glomerulus. reabsorbed by the peritubular capillaries. 10
107




Glomerular Tubular Tubular
filtration reabsorption secretion peritubular
capillary






glomerulus distal
convoluted
proximal
glomerular convoluted tubule
capsule tubule


H 2 O collecting
duct

H O
2
Reabsorption
of water



loop of
the nephron


renal pelvis

Excretion

108
FIGURE 18.3 Urine formation: filtration, reabsorption and excretion.

482 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

Along with blood pressure, the sodium content of the also increases the reabsorption of salt and water in the
extracellular fluid is critical in maintaining fluid balance, tubule and stimulates the release of renin.
as it constitutes the major electrolyte and osmotic agent
of the glomerular filtrate. It is imperative that sodium Antidiuretic Hormone
intake and loss is equally balanced, as excessive losses The antidiuretic hormone (ADH) is excreted from the
will result in associated fluid loss and excessive intake will pituitary gland under regulation of hypothalamic osmo-
result in fluid retention. If sodium balance is not main- receptors (thirst centre), and reduces kidney diuresis (the
tained, other compensations such as a rise in blood pres- excretion of water). By enhancing the kidney’s ability to
sure may result to restore fluid balance. As blood pressure concentrate urine, it ensures that the excretory functions
rises, the excretion of sodium also increases by way of the of waste products and electrolytes continue while limit-
production of additional glomerular filtrate. In this way, ing fluid loss. ADH is essential to surviving limited
water and sodium balance are inextricably linked. 10 periods of fluid deprivation and fine-tuning the urine
volume production on a continuous basis.
HORMONAL AND NEURAL REGULATION
OF RENAL FUNCTION Renin–Angiotensin–Aldosterone

Various feedback mechanisms exist that assist in precisely System (RAAS)
adjusting the final amount of fluid and electrolyte to be Renin is the chemical trigger to initiate a cascade system
excreted from the kidney. These include the sympathetic that results in two powerful hormones acting on the
nervous system response, angiotension II, aldosterone, kidney to significantly influence sodium and water excre-
antidiuretic hormone and atrial natriuretic peptide. All tion (see Figure 18.4). Renin is produced and released
these mechanisms work in synchrony with blood pres- from the juxtaglomerular apparatus, a collection of cells
sure and sodium balance in ensuring a highly regulated in the macula densa of the distal tubule, and the adjacent
circulating and extracellular fluid volume. 10 afferent arteriole next to the glomerulus, which monitors
blood sodium concentration. When released, renin stim-
Sympathetic Nervous System ulates the activation of angiotensin I from angiotensino-
Stimulation of the sympathetic nervous system (SNS) by gen. Under the influence of coenzyme A, angiotensin I
loss of blood volume occurs by reflex via the low-pressure converts to angiotensin II, a potent vasoconstrictor and
volume sensors in the pulmonary and venous circula- stimulus to reabsorb sodium and water. The vasoconstric-
tions. This is complemented by further stimulation if tor effect raises blood pressure and flow to the glomeru-
arterial pressure falls. The SNS widely innervates the lus, inhibiting further renin release (a negative feedback
kidney and is able to reduce the filtration rate by con- mechanism) as perfusion pressure normalises. This allows
stricting the afferent arteriole of the glomerulus, thus the return of natriuresis (sodium excretion) and diuresis.
inhibiting blood flow and pressure necessary to create the This response is essential in assisting with retaining fluid
glomerular filtration rate. This stimulation of the SNS in the event of a falling blood pressure, or boosting fluid



+
Low (Na ) ECF RBPF/P Renal sympathetic
Renin
Angiotensinogen release from the renal JG apparatus

Angiotensin I
Adrenal cortex + angiotensin II + ACE

Aldosterone release Vasoconstriction
Thirst
+
Na (Cl + H O)
2
reabsorb DCT & CD TPR
ADH
ECF volume BP

Abbreviations
ACE = angiotension-converting enzyme ECF = extracellular fluid
ADH = antidiurectic hormone JG = juxtaglomerular
BP = blood pressure RBF/P = renal blood flow/pressure
CD = collecting duct TPR = total peripheral resistance
DCT = distal collecting duct
FIGURE 18.4 Renin–angiotensin–aldosterone system (RAAS).

Support of Renal Function 483

+
excretion as blood pressure rises. It also responds effec- ammonia (NH 3 ) in the renal tubule to form ammonium
+
tively to a rise in sodium intake by reducing angiotensin (NH 4 ), which is unable to be reabsorbed. Coinciden-
+
II formation and allowing a larger natriuresis, resulting tally, raised H excretion increases the reabsorption of
in maintenance of sodium balance, a key to tissue fluid sodium, which increases the alkalytic ion, bicarbonate
−
distribution and balance. 10 (HCO 3 ). Conversely, during alkalosis the reabsorption
of hydrogen ions is increased. These changes in secretion
Aldosterone is a mineralocorticoid excreted from the
adrenal cortex in response to angiotensin II. Aldosterone of hydrogen ion concentration in the renal filtrate alter
increases the reabsorption of sodium, and hence water, the pH of the urine down to a maximum level of 4. The
+
in the cortical collecting tubules and increases the rate of buffering of H with ammonia reduces the acidifying
potassium excretion. This has a dual effect of regulating effect of the hydrogen ions, particularly as some ammo-
sodium balance and extracellular fluid volume. As fluid nium combines with chloride to form ammonium
10
volume accumulates, the rise in glomerular filtration rate chloride.
self-limits the volume effect by increasing both diuresis
and natriuresis. Role as an Endocrine Organ
The kidney has two homeostatic roles as an endocrine
Atrial Natriuretic Peptide organ. Although neither have effects relevant to acute
Atrial natriuretic peptide (ANP) is a hormone released illness, patients with chronic renal dysfunction often
need supplementation to overcome the loss of renal
from the atria of the heart in response to atrial stretching endocrine support. Erythropoietin is important in stimu-
during periods of increased circulating fluid volume. ANP lating the generation of new red blood cells and is released
is therefore often described as having an antagonising from the kidney in response to a sustained drop in arte-
effect to the RAAS (which acts primarily to preserve rial blood oxygen levels. Calcitriol helps regulate the
sodium and water). These natriuretic, and hence diuretic, absorption of calcium from the gut, which in turn pro-
effects are mild and self-limiting, and occur in response motes bone resorption of calcium and the reabsorption
to mild rises in GFR and reductions in sodium reabsorp- of calcium in the kidney. The kidney also acts to convert
tion. As blood pressure falls, the drop in GFR compen- vitamin D to its active form, which is necessary for the
sates for the effect of ANP, ensuring that excessive loss of maintenance of body calcium levels. 10
sodium and water does not occur. 10

Regulation of Acid–base and PATHOPHYSIOLOGY AND
Electrolyte Balance CLASSIFICATION OF RENAL FAILURE

The kidney assists in the management of body pH by Diseases of the kidneys affect structure and therefore the
−
+
regulation of the excretion of H and HCO 3 ions. While function of the nephrons in some way. Pathology such as
the renal response to alkalosis or acidosis is slow in com- this, if untreated, may not cause complete loss of renal
parison with plasma buffers and respiratory regulation function (i.e. ARF), but is dependent on the amount of
+
(see Chapter 13), it does result in a net loss of H ions or nephron damage or ‘injury’ occurring at the time of the
−
recovery of HCO 3 ions, which are the basis of human pH illness, and whether the patient has had any previous
11
balance (see Figure 18.5). During acidosis the kidney illness that resulted in undetected kidney damage. By
+
raises H secretion by active transport to combine with focusing on factors that resulted in kidney injury, both
individually and collectively, then more serious damage
that may result in failure can be averted. This concept is
more clearly described in the later section on ATN and
Capillary lumen Renal tubule AKI which includes the RIFLE Criteria. 1,2
The conventional classification of ARF is based on
the perceived causative mechanisms, as outlined by
numerous authors, 12,13 however, irrespective of causative
H2CO3 mechanism, the same renal replacement therapies are
Active
HCO 3 – transport suitable to treat this: 14
H + ● prerenal
H + H + ● intrarenal (intrinsic)
+ ● postrenal.
+
+ NH 3
NH 3 PRERENAL CAUSES
=
NH 4 + Prerenal factors affecting blood supply to the kidneys,
such as hypovolaemia, cardiac failure or hypotension/
shock, can cause ARF. The mechanism and outcome are
easily related. As blood flow to the kidneys is reduced,
Tubular epithelium
less glomerulofiltration occurs, urine production dimin-
ishes and wastes accumulate. This state can be reversed
FIGURE 18.5 Hydrogen ion regulation in the kidney. by restoration of blood volume or blood pressure. In the

484 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

short term (1–2 hours), nephrons remain structurally within the kidney, therefore reducing glomerular filtra-
normal and respond by limiting fluid lost by urine tion activity and affecting the reabsorption and diffusive
production while concentrating the excretion of waste process of the nephron. This reduction in blood flow is
products. The physiological process combines the neuro- exacerbated by degenerative vessel obstruction with ath-
endocrine control of the hypothalamus and the sympa- eromatous plaque, particularly pronounced in diabetic
thomimetic response, which then regulates both patients due to ineffective glucose metabolism. Diabetic
antidiuretic hormone secretion and the stimulation of patients are more likely to develop ARF associated with
the renin–angiotensin–aldosterone system (see Figure medical care in hospital from what may otherwise seem
18.4). This process is highly influenced by any preexisting to be a relatively trivial insult to the kidneys in a younger,
illness or concurrent factors such as diabetes and systemic healthy patient. The event may be enough to trigger ARF
infection. 12 in these patients, as they lack any degree of ‘renal reserve’
or tolerance to events such as low blood pressure or
INTRARENAL (INTRINSIC) CAUSES administration of nephrotoxic drugs normally filtered by
13
Intrinsic damage to the nephron structure and function the kidneys.
can be due to infective or inflammatory illness, toxic
drugs, toxic wastes from systemic inflammation in sepsis, POSTRENAL CAUSES
vascular obstructive thrombus or emboli. In differentiat- Urinary tract obstruction is the primary postrenal cause
ing this type of ARF, a process of elimination has been of ARF, and is uncommon in the critical care setting as it
13
suggested where failure of kidney function persists after is rarely associated with acute onset renal failure. Postre-
the restoration of adequate perfusion (blood flow), or nal obstruction is more common in the community and
where no loss of perfusion has occurred, and there is no is associated with urological disorders such as prostate
15
obstruction to urine flow. Diagnosis is made by exclu- gland enlargement in males, urinary tract tumours and
sion of other causes. The common causes of this type of renal calculi formation impairing urine outflow. It is
ARF, glomerulonephritis, nephrotoxicity and chronic vas- essential that blockage of any urinary drainage device be
cular insufficiency, are discussed below. excluded in the critically ill patient when undertaking an
assessment of apparent oliguria.
Glomerulonephritis
This condition is caused by either an infective or a non- ACUTE TUBULAR NECROSIS AND
infective inflammatory process damaging the glomerular ACUTE KIDNEY INJURY
membrane or a systemic autoimmune illness attacking Intrinsic ARF (described above) is often associated with
the membrane. Either cause results in a loss of glomeru- typical microscopic changes on pathology examination
14
lar membrane integrity, allowing larger blood compo- of kidney tissue. This pathology is termed acute tubular
nents such as plasma proteins and white blood cells to necrosis (ATN), and possibly explains how and why, in
cross the glomerular basement membrane. This causes a the acute setting, kidneys can fail abruptly to minimal to
loss of blood protein, tubular congestion and failure of no function (no urine output and therefore no waste
normal nephron activity. Resolution is based on treating clearance), and can then after a period of time, with arti-
the cause, such as an infection or autoimmune inflam- ficial support, recover to normal function in many
21
matory illness. 16 patients. This is an interesting area for current research
into the mechanisms responsible for acute kidney failure
Nephrotoxicity that are yet to be fully understood.
Nephrotoxicity occurs as a result of damage to nephron Acute tubular necrosis describes damage to the tubular
cells from a wide range of agents, including many drugs portion of the nephron and may range from subtle meta-
used in critical care (e.g. antibiotics, anti-inflammatory bolic changes to total dissolution of cell structure, with
agents, cancer drugs, radio-opaque dyes). Toxic prod- tubular cells ‘defoliating’ or detaching from the tubule
17
22
ucts of muscle breakdown in severe illness and trauma, basement membrane. Most ARF is multifactorial in
commonly called Rhabdomyolysis (see Chapter 23 for origin and may involve more than one causative mecha-
15
trauma association), 4,13,18 blood product administration nism and is not always an ischaemic or necrotic event.
reactions and blood cell damage associated with major In critical illness, the most common combination causing
surgery are also causative agents. As these agents may ARF is the administration of nephrotoxic agents in
19
often be given concurrently, a cumulative effect, along association with prolonged hypoperfusion or ischaemia
22
with intermittent falls in renal perfusion, may result in (oxygen deprivation). This type of tubular necrosis can
the development of intrinsic ARF. be further mediated by infection, blood transfusion reac-
tions, drugs, ingested toxins and poisons, or be a compli-
Vascular Insufficiency cation of heart failure or major cardiovascular surgery.
One-third of patients who develop ARF in the ICU have The initial insult can also be compounded by metabolic
disturbances and subsequent systemic infection.
20
chronic renal dysfunction. This chronic dysfunction
may be undiagnosed prior to the critical illness, and may ATN is the causative mechanism for up to 30% of acute
23
be related to diabetes, the ageing process and/or long- kidney failure in the intensive care setting, with the
term hypertension. These factors create a reduction in precise causative illness not easily identifiable in critically
both large and microvasculature blood flow into and ill patients with multiple co-morbidities, for example

Support of Renal Function 485

diabetes, advanced age, investigations requiring radio- before death in a response known as apoptosis (cell self-
21
opaque dye administration, potent and nephrotoxic drug death) (see Chapter 21). The response is aimed at organ
administration or major surgery with an inflammatory survival, with some individual cells ‘sacrificing’ them-
state due to an underlying infection. This is the context selves during a period of crisis. This protective response
of critical illness and ARF where, despite modulation of reduces oxygen demand by initiating cell death in some
the cause and support with artificial renal replacement tubules, while others differentiate and/or proliferate for
therapies, mortality ranges from 28–90% depending on repair, and allows continuation of some normal function.
diagnostic criteria or definition. 3,24,25 If the causative process abates, remaining cells regenerate
by differentiation and proliferation, tissue repair occurs
This type of kidney damage is of particular importance, with restoration of normal epithelium in some tubules
as ATN is abrupt in onset and causes a rapid cessation of and nephron function returns.
normal nephron function, a picture typical of any critical
illness and failure of other body organs. As this failure is During this period cellular ‘debris’ collects in the tubule
commonly mediated by a loss in total or regional blood loops, causing obstruction of tubular flow, with backleak
26
flow to the kidney, it is more pronounced in the kidney of filtrate occurring through the ‘patchy’ exposed tubular
medulla or outer regions sensitive to reduced blood flow. membrane surface. An inflammatory process is also
The cause of this loss in blood flow may be multifactorial stimulated due to release of cell adhesion factors and
27
but is commonly associated with shock and consequent leucocyte activation, which in turn causes further vaso-
28
low blood pressure (see Figure 18.6). Tubular cells suffer constriction and ischaemia in the acute stage. The back-
an ischaemic insult, causing a shedding of the cells from leakage and static tubular fluid creates a concentrate that,
the nephron basement membrane. This shedding of cells by diffusion, raises blood levels of wastes such as urea,
has an initial loss of cell polarity, and then cell death, creatinine and other toxins. Along with this cessation of
with a ‘patchy’ occurrence along the tubule basement urine flow, toxicity occurs with high serum levels of
21
membrane. In addition, some cells detach themselves wastes such as urea, creatinine, potassium and undefined






Shock state detected Hypothalamus


Sympathoadrenal Post. pituitary – ADH
medullary response Ant. pituitary – ACTH

SNS


Adrenal medulla Adrenal cortex



Noradrenaline Adrenaline Glucocorticoids
Protein catabolism

Vasoconstriction HR, myocardial
Cool pale skin, BP contractility
BSL Gluconeogenesis
ACTH Altered immune activity

Serum osmolality Aldosterone
Renal blood flow +
Renin, angiotensin Hypothalamus Na retention
Post. pituitary
Vasoconstriction H2O retention
ADH Blood volume
Oliguria
Abbreviations
ACTH = adrenocorticotrophic hormone HR = heart rate
+
ADH = antidiuretic hormone Na = sodium
BP = blood pressure SNS = sympathetic nervous system.
BSL = blood sugar level

FIGURE 18.6 Neuroendocrine response to shock, resulting in oliguria.

486 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

27
toxins. This is the clinical state of ARF associated with Nurses in the critical care setting who measure urine
the pathology of ATN and now referred to as acute kidney output hourly, readily recognise a key sign of impending
injury (AKI) to better describe the total ‘picture’ of pre- renal dysfunction. Oliguria in the absence of catheter
illness status, immediate causative events and degree of obstruction should be responded to quickly, as this sug-
injury determined by patient serum creatinine or urine gests inadequate kidney blood flow and to some extent
output. 1,2 is a delayed observation considering the continual
moderation of kidney function producing urine output.
11
Some authors prefer the term ‘ATN’ to describe ARF, Persisting oliguria or the onset of anuria with associated
using it as a surrogate for ARF in the acute setting, as it rises in blood creatinine defines renal failure. This sequence
focuses on the pathophysiology of tubular damage, recog- of events can be identified in a criteria pathway published
nising this damage as a final outcome of all causative following a consensus meeting of physicians. The ‘RIFLE’
factors. However, more recently, with the development of criteria – risk, injury, failure, and outcome criteria of loss
32
a consensus definition for ARF describing stages of illness and end-stage disease – provides an increasingly widely-
severity, the term acute kidney injury (AKI) is now used accepted approach to diagnosing and classifying ARF.
reflecting pathophysiology, the outcome of many caus-
ative factors, and the clinical context where small derange- CONSENSUS DEFINITION: THE RIFLE CRITERIA
ments may be evident with reversibility of dysfunction
and recovery, through to irreversible damage with kidney The RIFLE criteria are indicated in Figure 18.7, and use
failure. 1,2 raising creatinine and lowering urine output as highly
sensitive and specific indicators for a continuum of renal
The kidneys are vital human body organs essential to failure. This is a useful classification system to grade
sustaining life. An important interrelationship of the loss of kidney function, reflecting stages of injury to
kidneys and other body organs exists, with the brain, the kidney before failure occurs. Without this, the small
heart, liver and lungs dependent on receiving ‘clean’ but important losses of kidney function before the failure
1
blood to function. As toxins accumulate in ARF these state are not adequately considered. This approach
organs become dysfunctional, 29,30 although many of provides a consensus definition for loss of kidney func-
these interrelationships (e.g. the liver) are poorly tion that is useful for clinical practice and research into
understood. 31 this area, with clinicians all talking the same ‘language’
when comparing patients and/or results from clinical
ACUTE RENAL FAILURE: CLINICAL trials. The shape of the diagram indicates that more
people will develop symptoms of ARF linked to kidney
AND DIAGNOSTIC CRITERIA FOR ‘injury’ and be considered ‘at risk’ (high sensitivity) than
CLASSIFICATION AND MANAGEMENT those at the bottom of the definition, who are fewer
in number but need to fulfil strict criteria (high
CLINICAL ASSESSMENT specificity).
Clinical assessment of the patient with impending renal To better understand the RIFLE criteria in a clinical care
failure can involve myriad tests and investigations; context, the following discussion is useful to consider in
however, the majority of these are not used to assess the association with a review of Figure 18.7. In a hospital
critically ill patient. The clinical history is important in setting, those patients with a risk of renal injury would
differentiating preexisting renal disease and cataloguing be identified by a low urine output of less than 0.5 mL/
the numerous factors already discussed that can contrib- kg/h for 6 hours. In this situation their creatinine would
ute to renal dysfunction. As the majority of renal failure be expected to rise, indicating a concurrent reduction in
patients in the ICU will succumb to the combination of glomerular filtration rate. Reducing renal risk requires
prerenal renal failure and ATN, the key assessments used basic measures such as increasing their fluid intake and
in monitoring renal function are urine output, serum continuing to closely monitor urine output, whilst review-
creatinine and urea levels, combined with more general ing the patient’s medications, haemodynamic state and
haemodynamic measures including HR, CVP, BP, PCWP. possible other causes of injury in order to prevent further
These measures are essential for the critically ill patient, deterioration.
and alterations provide the diagnostic key. They also link
into the wider assessment of fluid and electrolyte balance, In the event that urine output decreases further, or was
as described in Chapters 9 and 19. worse than this when first identified, with less than
0.5 mL/kg/h or a creatinine increase of twice the normal,
DIAGNOSIS renal injury is likely, with these clinical changes proposed
as being highly sensitive towards injury occurring. At this
The management of ARF begins with making the diagno- stage the above measures would be appropriate and
sis, based on the patient’s presenting signs and symptoms requires further investigation into the cause. With close
linked to a patient history. A long-term history of renal monitoring, support of haemodynamics and fluid admin-
disease involving urinary tract infections, diabetes, cardiac istration, most patients should not progress further in the
failure and systemic inflammatory illnesses are all highly failure continuum.
11
relevant. Immediate history of presentation to a hospi-
tal involving surgery or any life-threatening illness with The next progression in clinical deterioration is oliguria,
associated shock is also highly relevant in association or urine output being less than 0.5 mL/kg/h for 24 hours
with reduced urine output volumes over time. or anuria for 12 hours. The creatinine increase is now

Support of Renal Function 487



GFR criteria* Urine output criteria

Risk Increased s. creat 1.5 or UO <0.5 mL/kg/h
GFR decrease >25% 6 h
High
sensitivity
Injury Increased s. creat 2 or UO <0.5 mL/kg/h
GFR decrease >50% 12 h

Increased s. creat 3 or UO <0.3 mL/kg/h
Failure GFR decrease 75% 24 h or
OR s. creat 4 mg/dL Anuria 12 h Oliguria
Acute rise 0.5 mg/dL
High
specificity
Loss Persistent ARF** = complete loss
of kidney function >4 weeks


ESKD End-stage kidney disease
(>3 months)




32
FIGURE 18.7 Criteria for diagnosis of acute renal failure: the risk, injury and failure criteria with outcomes of loss and end-stage renal disease (RIFLE).

proposed as being three times the normal level, and, kidney damage or complications of functional renal
with minimal to no urine output, renal ‘failure’ is pro- deterioration.
posed as a clinical diagnosis using this criterion. It is at CLINICAL MANAGEMENT
this stage when renal replacement therapy would need to
be considered and, if necessary, to transfer patients to In the critically ill patient, kidney function failure may
ICU. A continuous therapy, or continuous renal replace- be associated with an initial renal response to a fall
ment therapy (CRRT), is recommended. This term is in perfusion associated with systemic shock. As the
more specific for the modes of treatment commonly majority of patients recover their renal function from
8
applied in the ICU. Renal replacement therapy (RRT) ICU ARF, initial clinical management is aimed at reduc-
refers to any treatment that replaces renal function and ing further renal damage. If kidney function becomes
includes intermittent haemodialysis (IHD) and perito- so compromised that blood pH, fluid and electrolyte
neal dialysis. It is also important to understand that in balance cannot be sustained, then a replacement therapy
the setting of an acute illness, many patients progress will need to be introduced. This is continued until
through these stages of renal dysfunction to the failure kidney function is marked by the return of urine
stage quickly and/or the problem is unidentified until production or patients are moved to a more chronic
the failure stage is met. The timing for taking a blood form of replacement therapy, such as intermittent
sample to measure creatinine or when a urine catheter is haemodialysis.
passed to measure urine output also influences this iden- Reducing Further Insults to the Kidneys
tification. The diagnosis may be made only at the failure
stage, without any identifiable period of risk or injury as After diagnosis, the next management principle is to
proposed by the RIFLE criteria. With a critical illness, remove or modify any cause that may exacerbate the
serum values of creatinine, urea, pH and potassium are pathological process associated with ARF. Further inter-
readily available in the ICU and are used for diagnosis in ventions and investigations are performed in relation to
association with the RIFLE definition. Daily monitoring the findings from the history and presentation. These
13
of these values as a minimum is necessary for diagnosis may include:
and monitoring during CRRT in the ICU. The normal ● further intravenous fluid resuscitation (despite an
laboratory values for these biochemical markers is essen- oligo-anuric state) and restoration of blood pressure
tial knowledge for nurses to understand renal failure and ● physical or diagnostic assessment for renal outflow
management. obstruction and alleviation if present
● ceasing or modifying the dose of any nephrotoxic
Treatment with CRRT may not be implemented until drugs or agents and treating infection with alternative,
failure is evident, by anuria and uraemia, or until patients less toxic antibiotics.
meet the RIFLE definition criteria. However, in
some patients, CRRT may be commenced earlier, in antic- Initial management strategies for developing ARF remain
ipation of failure and as a strategy to prevent further conservative, with careful management of fluid (once

488 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

adequate circulating volume is assured by initial fluid RRT urgent and mandatory. Combined derangements
resuscitation) and haemodynamics, encouraging diuresis can create the necessity to commence therapy before
if present, monitoring blood profiles for changes in urea individually-defined limits have been reached. Early ini-
and electrolytes, and limiting or reformulating the tiation of treatment is widely advocated and may confer
adminis tration of agents that may contribute to the accu- more rapid renal recovery.
mulation of urea and electrolytes (e.g. enteral or IV nutri-
tional supplements). The use of agents such as mannitol, RENAL DIALYSIS
dopamine and frusemide, while popular in practice, have
not been shown to be of any value in improving outcome Despite its complex physiology, human kidney function
in patients at risk of ARF. 13,20 is able to be largely replaced with a management program
that includes an artificial process of RRT that can sustain
Despite these efforts, life-threatening biochemistry may individuals for many years in the community setting. In
arise in ARF, such as severe acidosis and hyperkalaemia critically ill patients with ARF, this program focuses pre-
(a pH of <7.1 and a serum potassium >6.5 mmol/L) that dominantly on RRT, rather than on the endocrine func-
requires immediate treatment and can be an indication tions of the kidney.
for beginning RRT without elevation of serum creatinine
and oliguria and fluid overload. 33 HISTORY
Dialysis is a term describing RRT and refers to the purifi-
NUTRITION cation of blood through a membrane by diffusion of
36
When ARF is persistent, providing nutritional support waste substances. Table 18.1 outlines the historical
is another important management strategy. A review events in the development of dialysis. The Kolff rotating
of nutrition in ARF suggested that an intake of 30–35 drum kidney, one of the earliest attempts at RRT (illus-
kcal/kg/day and a protein intake of 1–2 g/kg/day is essen- trated in Figure 18.8), used cellulose tubing rolled around
tial due to the combined increase in protein catabolism a wooden skeleton built as a large, drum-styled cage. Cel-
34
and caloric requirements of associated critical illness. lulose acetate (material similar to ‘sticky tape’) tubing was
This nutrition is provided by the enteral or parenteral strong, did not burst under pressure and could be steril-
37
route and constitutes an increase in body fluids and nitro- ised. The drum with the blood-filled cellulose tubing
gen load. Ironically, this aspect of managing ARF in criti- wound around it was immersed in a bath of weak salt
35
cal illness may also be an indication for starting RRT solution, and as blood passed through, the rotating cel-
(see Chapter 19 for further discussion on nutritional lulose tubing allowed waste exchange to occur by diffu-
requirements in critical illness). sion. This method and the diagram included is useful
information as it is essentially the key concepts for how
RENAL REPLACEMENT THERAPY

If conservative measures fail, then the ongoing manage-
ment of the patient with ARF requires RRT. This enables
control of blood biochemistry, prevents toxin accumula-
tion, and allows removal of fluids so that adequate nutri-
tion can be achieved. The criteria and indications for
initiating RRT are listed in Box 18.1. One indication
is sufficient to initiate RRT, while two or more make




BOX 18.1 Proposed criteria for the initiation
of renal replacement therapy in adult
critically ill patients 14

● Oliguria (urine output <200 mL/12 h)
● Anuria/extreme oliguria (urine output <50 mL/12 h)
+
● Hyperkalaemia (K >6.5 mmol/L)
● Severe acidaemia (pH < 7.1)
● Azotaemia (urea > 30 mmol/L)
● Clinically significant organ (esp. lung) oedema
● Uraemic encephalopathy
● Uraemic pericarditis
● Uraemic neuropathy/myopathy
+
● Severe dysnatraemia (Na >160 or <115 mmol/L)
● Hyperthermia
● Drug overdose with dialysable toxin
71
FIGURE 18.8 Kolff dialyser.

Support of Renal Function 489



TABLE 18.1 Historical events in the development of dialysis

Time period and developer Description
1854: Thomas Graham, Scottish First used the term ‘dialysis’ to describe the transport of solutes through an ox bladder, which drew
chemist attention to the concept of a membrane for solute removal from fluid.
1920s: George Haas, German physician First human dialysis was carried out, performing six treatments on six patients. Haas failed to make
further progress with the treatment but is recognised as an early pioneer of dialysis.
1920–30s Synthetic polymer chemistry allowed development of cellulose acetate, a membrane integral to the
further development of dialysis treatments.
1940s: Willem Kolff, Dutch physician The discovery of heparin, an anticoagulant, enabled further development of dialysis during World
War II, the Kolff rotating drum kidney.
1940–50s: Kolff and Allis-Chalmers, USA Further modification of Kolff dialyser and the development of improved machines.
1950s: Fredrik Kiil, Norway Developed the parallel plate dialyser made of a new cellulose, Cuprophane. This required a pump to
push the blood through the membrane and return the blood to the patient.
1950–60s Dialysis began to be widely used to treat kidney failure.
1960s: Richard Stewart and Dow The hollow-fibre membrane dialyser used a membrane design of a cellulose acetate bundle, with
Chemical, USA 11,000 fibres providing a surface area of 1 m . 2
1970s Use of first CAVH circuits for diuretic resistant oedema by Kramer
1980s First continuous therapies using blood pump and IV pumps to control fluids removal and
substitution: Australia and New Zealand led the way
1990s New purpose built machines used; Gambro Prisma, Baxter BM 11 + 14 to provide pump controlled
therapies with integrated automated fluid balance using scales to measure fluids. Cassette circuits,
automated priming; new membranes
2000 Further purpose built machines using direct measurement for waste and substitution fluids via
Hygieia–Kimal machine. Introduction of high fluid exchange rates for sepsis treatment.
introduction of dialysis based machines in ICU for daily ‘hybrid’ treatments: SLEDD and SLEDDf
2010 Multiple CRRT machines; more advanced graphics interface and smart alarms. Waste disposal
systems. High flux, porous membranes



dialysis is today with modern machines and dialysis millions of people who suffer acute and chronic kidney
membranes. A major impediment to the safe use of this failure. 39,40
system was, however, the large amount of patient blood
required in the tubing and membrane. Historical Perspectives of Dialysis Nursing
This large extracorporeal blood volume became a focus Key to the application of these technical and scientific
for further development of the therapy. The goal was to developments has been the role of nurses, who have
develop a membrane for solute exchange with a greater made a substantial contribution to the safety and effi-
surface area than the cellulose membrane used by Kolff ciency of dialysis. Barbara Coleman is recognised as the
but needing less blood volume. This led to the develop- first dialysis nurse to publish a treatment protocol for
ment of the hollow-fibre filter membrane structure in the dialysis using the rotating drum machine in 1952. 39,41
1960s, the same design concept that is used today. Since Nursing of dialysis patients has developed into a special-
then significant developments have occurred, with new ist field of knowledge and skill, with nurses combining
fibres using the polymer polysulfone or other artificial their holistic view of patient management with the spe-
synthetic chemical structures that better imitate the cialist needs of patients with renal failure, from the out-
42
nephron glomerulus and the ability to transfer wastes patient setting to the ICU, including a collaborative
and plasma water for an effective ‘artificial kidney’. approach to further adaptations of dialysis best suited to
38
the critically ill. 43,44
This combination of extracorporeal circuit (EC), blood
pump and filter membrane (or artificial kidney or dialy-
ser), and the associated nursing management is now Development of Renal Replacement
commonly known as haemodialysis. The major treat- Therapy in Critical Care
ment components are essentially the same as those first Improvements in many fields of health care, including
developed in the 1960s, with the key component being resuscitation and treatment for shock, and the growing
the device membrane. Over the past 50 years, industrial number of patients undergoing and surviving extensive
and scientific developments such as plastics moulding surgery and trauma, have led to developments and chal-
and electronics have made current dialysis techniques lenges in critical care practice. Many patients who would
safe, effective and a life-sustaining treatment for the previously have died from an acute illness now survive,

490 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

but develop ARF as a complication, or coexisting organ addition to their established role in ICU of caring
failure secondary to a primary problem with their heart for critically ill patients using mechanical ventilation
or other major organ system. The pathogenesis and epi- and haemo dynamic interventions. Physician-prescribing
demiology of ARF have thus changed. rights also favoured this role for nursing in Australia and
New Zealand, as the ICU physician can prescribe renal
Historically, ARF was treated in the ICU with the use of
peritoneal dialysis (PD), which did not require specialist dialysis without the referral of the patient to a nephrolo-
8,49,50
nurses or physicians. This simple technique removes gist that is required in other countries. In the Austra-
45
wastes by infusing a dialysis fluid into the abdomen, lian context, this resulted in the provision of renal support
allowing diffusion and osmosis to occur between the for critically ill patients by ICU nurses alone, or in a
50
peritoneum and fluid before draining out again in shared role with renal dialysis nurses.
46
repeated cycles. This was performed by the ICU nurse Different approaches or models of care are created by
and prescribed by ICU physicians, but was inadequate in many factors, including the presence of a dialysis service
its clearance of waste and fluid volume, and was associ- in a hospital, the number of patients requiring treatment
ated with infection, limiting respiratory function and in an ICU per annum, physician rights of prescribing as
exacerbated glucose intolerance. 14,47 specified by health insurance scheme structures, and the
number, professional competence and flexibility of the
In 1977 Peter Kramer, a German ICU physician, frustrated nursing workforce available for an ICU or dialysis service
with the limitations of PD and the delays in gaining a in a given hospital. 44,50,51
dialysis nurse and machine to attend the ICU, developed
a new dialytic technique by inserting a catheter into the
femoral artery and allowing blood to flow to a membrane Refinement of Renal Replacement Therapy
and back to the femoral vein. As the blood passed through Although CAVH as developed by Kramer was useful in
48
the membrane, plasma water was filtered out. The tech- removing excessive body water and some wastes, a dialy-
nique was called continuous arteriovenous haemofiltra- sis blood pump enabled a much more efficient technique
tion (CAVH). It was later renamed slow continuous for therapeutic benefit in the ICU patient with ARF. The
ultrafiltration (SCUF), as it enabled the removal of plasma use of roller blood pumps to generate pressure and a reli-
water in addition to dissolved wastes (convective clear- able flow of blood, thus eliminating the need for arterial
ance of solutes) at a flow rate of 200–600 mL/h by passive puncture and access, was introduced by two German
drainage from the membrane as blood flowed through it. groups. This approach, termed continuous veno-venous
49
Kramer reported ‘considerable therapeutic potential’ after haemofiltration (CVVH), could reliably pump blood at
treating 12 patients in the ICU, although suggesting that a constant rate and achieve ultrafiltration volumes of
this level of ultrafiltration and waste clearance was inad- 1000 mL/h. This therapy was able to remove large volumes
equate for optimal support of ARF in many critically ill of plasma water and, if run continuously with similar
6
patients. This marked the beginning of continuous RRT amounts replaced by a balanced plasma water substitute,
in the ICU as an intervention prescribed and managed by an effective clearance of wastes similar to a high-intensity
ICU nurses and doctors for patients with ARF. A sche- dialysis treatment could be achieved without cardiovas-
matic diagram of Kramer’s original technique is illus- cular instability.
trated in Figure 18.9.
With further modifications to the circuit and filter set-up,
The increase in demand for chronic renal failure dialysis a diffusive component was added to the therapy by
made it problematic to provide any service to patients in running a dialysate volume through the haemofilter,
the ICU with ARF by dialysis nurses. Dialysis for patients flowing between the membrane fibres and countercurrent
in the ICU was often delayed or unavailable while using to blood flow. This was termed continuous veno-venous
the same human and material resources from a dialysis haemodiafiltration (CVVHDf). To deliver continuous
unit. It was thus inevitable that in the ARF context ICU forms of veno-venous RRT required the introduction of
49
nurses would adopt the role of the dialysis nurse, in blood pumps from modified dialysis machines into the
ICU, and created a major education and training need for
52
critical care nursing. This was first met in the Australian
setting by dialysis nurses until independent practice was
CAVH achieved. This training often used old dialysis machines
and equipment that had been superseded in the chronic
dialysis setting by new, more efficient dialysis machines.
The old machines were suitable for the ICU to use because
of their technical simplicity, with low or no purchase
42
cost. As CRRT became more widespread in the ICU, this
encouraged manufacturers to design and market purpose-
built CRRT machines with automation, intelligence soft-
Filtrate ware for alarm detection and practical solutions. 53
Convection
As already noted, in the Australian and New Zealand
setting CRRT is provided by ICU nursing staff with
FIGURE 18.9 CAVH used in the ICU in the late 1970s. Patient arterial blood
pressure provides flow to the membrane, and blood returns via a large vein. medical prescription by ICU physicians, with nephrolo-
Plasma water removal occurs via filtration and is pressure-dependent. gists focused on chronic disease and care of patients
48

Support of Renal Function 491

outside the ICU. In North America, CRRT is not always ● a surgical joining of an artery and vein (usually in the
the preferred choice for supporting ARF in ICU, and inter- forearm), making a large vessel that is punctured with
54
mittent dialysis techniques prevail. As a result of this needles to both draw and return the blood (AV fistula)
mixed application of techniques, there have been a ● a catheter with two lumens to draw and return blood
63
number of publications highlighting the success, utility via a large central vein (veno-venous access
and methods for CRRT in the ICU setting, 47,55,56 with a catheter).
smaller number of publications either making compari- In the acute renal failure setting and where temporary
sons between approaches or continuing to support inter- treatment is anticipated, the two-lumen catheter is
mittent techniques using dialysis in the ICU. 57-60
recommended. 8,64
While this application of both CRRT and intermittent
haemodialysis (IHD) has prevailed for the management HAEMODIALYSIS, HAEMOFILTRATION AND
of ARF, new ‘hybrid’ approaches have evolved that HAEMODIAFILTRATION
combine some benefits of both CRRT and IHD, but also
do suffer from the compromise nature of the approach. There are numerous approaches to the delivery of RRT.
These are daily, limited time frame treatments, with one Haemodialysis, haemofiltration and haemodiafiltration
variant of the approach termed EDDf (extended daily are three common techniques used to achieve artificial
diafiltration), which provides a further treatment option kidney support in ARF. The basic blood path or circuit for
for ARF in the ICU. While daily treatments are emerging these therapies is indicated in Figure 18.10 and is useful
as the only method of RRT for ICU patients in a limited to review as a basis for understanding each of the three
number of hospitals 59,61,62 evidence as to their utility in circuits for each therapy and where the RRT fluids are
treating the most critically ill patients is lacking. This then applied to this circuit differentiating them as alter-
means that continuous forms of RRT prevail as the com- native techniques.
monest method for treating ARF in the ICU in Australia The extracorporeal component is a common factor in all
and Europe. these different circuit designs. The difference between
APPROACHES TO RENAL treatments is how the solutes (urea, creatinine and other
waste products) and solvent (blood plasma water) are
REPLACEMENT THERAPY removed from the blood as it passes through the filter
membrane (artificial kidney), and the intermittent versus
Both IHD and CRRT require a machine to pump blood continuous prescription of the therapy. This is deter-
and fluids; pressure and flow devices to monitor treat- mined by the way in which the dialysis fluids are mixed
ment; a tubing and filter membrane set that together with or exposed to the blood, the rate and direction of
create an extracorporeal circuit (EC) (outside the body blood and fluid flows, and how fluid loss or a negative
blood pathway); and a catheter connecting the patient’s fluid balance is achieved. The three physical mechanisms
circulation to the circuit (see Figure 18.10). This catheter of fluid and solute management are convection, diffu-
enables blood to be drawn from and returned to the sion, and ultrafiltration. Table 18.2 lists the commonly-
patient (known as ‘access’). Access can be achieved by used abbreviations to describe the timing of treatment,
three different techniques: blood access for the therapy and mode of solute removal.
● temporary catheters inserted via a skin puncture into
an artery (A) for drawing blood and a vein (V) to Convection
return the blood (AV access) Convection is the process whereby dissolved solutes are
removed with blood plasma water as it is filtered through
the dialysis membrane. The word is derived from the
Latin convehere, meaning ‘to remove or to carry along
65
EC blood path with’. This process is very similar to that occurring in the
native kidney glomerulus, as plasma water is filtered

Membrane
TABLE 18.2 Abbreviations describing modes of renal
Blood pump replacement therapy
and fluids monitor
Timing of Mechanism of solute
Return blood therapy Route of access removal
to patient
I = intermittent A = arterial H (or HF) = haemofiltration
C = continuous V = venous – convection
Blood from patient S = slow AV = arteriovenous D (or HD) = haemodialysis
VV = veno-venous – dialysis
HDF = haemodiafiltration
Access to patient – diffusion and
convection
UF = ultrafiltration –
FIGURE 18.10 Renal replacement therapy blood path circuit common to plasma water removal
all approaches.

492 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



Replacement
CVVH
CVVH
fluids
R.O K +
Blood Tap
Pump –
water HCO 3
Membrane Blood
pump
Pre & Post

Waste = Qdf + UF


Filtrate Heater
IHD

FIGURE 18.11 Continuous veno-venous haemofiltration (CVVH) circuit.
FIGURE 18.12 Intermittent haemodialysis circuit. RO = reverse osmosis
across the nephron tubule via the Bowman’s capsule. In
RRT, the plasma water with the dissolved wastes is dis- ‘treated water’.
carded; the plasma water deficit is then replaced with
manufactured artificial plasma water in equal or slightly blood flow is not useful unless dialysate flow is also
lower amounts to achieve a desired fluid balance. This increased, as more waste solutes will not be cleared if the
blood washing (purification) process is commonly dialysate fluid and blood are in diffusive equilibrium. The
known as haemofiltration. When applied on a continu- technique of solute removal using diffusion alone is
ous basis in the ICU, haemofiltration can adequately termed dialysis; when used with blood, the process is
replace essential renal functions, and is particularly termed haemodialysis (HD). When applied on an inter-
effective in managing fluid balance. 66-70 Figure 18.11 illus- mittent basis, as is normal for patients receiving RRT for
trates the circuit and set-up for continuous veno-venous chronic renal failure, it is called intermittent haemodialysis
hemofiltration.
72
(IHD). Figure 18.12 illustrates the circuit set-up for IHD.
Diffusion Ultrafiltration
Diffusion refers to the physical movement of solutes Ultrafiltration is the process that allows plasma water to
across a semipermeable membrane from an area of high leave the blood, achieving body fluid or water loss. Dialy-
concentration to that of a relatively low concentration; sis nurses measure a fluid loss by weighing the patient
66
71
that is, solutes move across a concentration gradient. A before and after a treatment. This process is primarily
higher concentration gradient results in a greater rate of used to achieve fluid balance, an important function of
diffusive clearance. As blood passes through the dialysis the kidneys. 33,66 The only difference between this process
membrane, dialysate fluid, reflecting normal blood chem- and the convective clearance of solutes is that this fluid
istry, is exposed to the blood on the opposing side of the is not replaced, and it is therefore not considered an
membrane fibre. Diffusive clearance is continuous as adequate solute management method. Ultrafiltration
solute exchange occurs by diffusion with the dialysate cannot be undertaken in large amounts without fluid
fluid and the blood continually moving in and out of the replacement, as it would cause hypovolaemia. It is there-
membrane. As ‘dirty’ or waste-laden blood enters the fore implemented during a dialysis period by removing
membrane and ‘clean’, fresh dialysate is in continuous small amounts each hour (e.g. 250 mL/h for 4 hours) of
supply, this process performs an effective waste-removal the intermittent treatment cycle.
process. The two mediums are usually established in a
countercurrent or opposing flow to each other, making There are different therapeutic effects from each form of
diffusion another process, mimicking the normal nephron RRT and different operational prescriptions of blood and
function of the kidneys. 71 fluid flow. Combinations of convection and diffusion can
66
be used, known as haemodiafiltration (CVVHDf). An
Diffusive clearance technique can be performed with increase in the diffusive component (i.e. raising the dialy-
increasing intensity and effect by making the blood and sate flow rate in CVVHDf) will increase the removal of
dialysate flow faster, with technical problems associated small-molecular-weight substances such as potassium
with delivering the high fluid and blood flow being the and assist with hydrogen ion exchange via buffer solu-
main limiting factor increasing clearance. The two flows tion. This can also be achieved via increasing filtration
need to be maintained in relation to each other; for the fluid flow (convective clearance), which will also add an
diffusive clearance to be efficient the dialysate flow must increase in clearance of larger molecules, for example
always equal or exceed the blood flow. A common setting those associated with severe infection and systemic
for an intermittent dialysis treatment would be a blood inflammation or sepsis. Figure 18.13 illustrates the circuit
flow and dialysate fluid flow of 300 mL/min each. A faster and set-up for CVVHDf.

Support of Renal Function 493

MAJOR CIRCUIT COMPONENTS FOR CRRT weight <20,000 daltons), while larger plasma proteins
65
To correctly use and ‘troubleshoot’ the various modes of and blood cells (at least 60–70,000 daltons) are retained.
RRT, nurses must have a clear understanding of the circuit Plasma water separated from the blood in this way is
components and their function. carried away from the filter by a side exit port and a pump,
where it is measured and directed into a collection bottle
Membranes or bag as waste; this convective clearance of solutes is
The filter or haemofilter (blood filter) is the primary func- similar to urine produced by the normal kidneys. The
tional component of the RRT system, responsible for sepa- plasma water loss is replaced in equal volume with a
rating plasma water from the blood and/or allowing the commercially-manufactured plasma water substitute,
exchange of solutes across the membrane by diffusion. either after the ‘filtered’ blood exits the haemofilter (post-
The filter is made of a plastic casing, containing a synthetic dilution) or prior to the blood entering the haemofilter
polymer inner structure arranged in longitudinal fibres. (predilution) or both at the same time. The plasma water
A schematic diagram of a haemofilter is shown in replacement contains no metabolic wastes and achieves
67-70,73
Figure 18.14. The fibres are hollow and have pores along blood purification as it is continuously replaced.
their length with a size of 15,000–30,000 daltons. This Filter membrane polymers are of different materials:
allows plasma water to pass through, carrying dissolved AN69 (acrylonitrile/sodium methallyl sulfonate), PAN
wastes out of the blood (most of which have a molecular (polyacrylonitrile) or PA (polyamide), and polysulfone;
74
however, all demonstrate similar artificial kidney effects
and are generally applied according to the physician’s
42
Dialysate CVVHD(F)-diffusion and convection preference. The most important characteristics of filters
used in continuous modes of therapy are: (a) a high
Replacement plasma water clearance rate at low blood flow rates and
Fluids circuit pressures; and (b) high permeability to middle-
Heater sized molecular weight substances (500–15,000 daltons,
e.g. inflammatory cytokines), which are often encoun-
Blood tered in critical illness.
Pump
Vascular Access
As previously noted, in order to establish CRRT it is neces-
sary to create a blood flow outside the body using the EC.
Blood is most commonly accessed from the venous circu-
lation of the critical care patient via a catheter placed in a
Heater
Diafiltrate central vein (e.g. femoral). Blood is both withdrawn from
the vein and returned to the same vein – that is, veno-
venous (VV) access by means of a double (dual)-lumen
catheter. When the same procedure is carried out by
70
FIGURE 18.13 Continuous veno-venous haemodiafiltration (CVVHDf)
circuit. accessing the blood from the patient’s systemic circulation



Membrane casing Blood space

Potting agent Fibre holes




(blood flow)






Membrane fibre Blood tubing
connection
Port for dialysate or plasma
water removal


FIGURE 18.14 Haemofilter (dialysis membrane). Cross-sectional view indicating longitudinal synthetic fibres conveying blood into and out of the plastic
casing outer structure. Plasma water is removed via the side ultrafiltrate port during CVVH applying convective clearance. In CVVHDf, the blood is exposed
to fluid via the membrane fibres so that diffusive clearance can occur.

494 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E
























A
CRRT vascular access catheter
lumen design profiles


Double ‘D’ design or ‘D’ and ‘O’ : one
lumen extended longer for return blood



Inner and outer lumen : ‘Coaxial’ with
side holes at tip for drawing blood int
outer lumeno



Side by side : Double ‘O’ :one FIGURE 18.15 (A) Vascular access catheters for CRRT. Dual-lumen, Bard® Niagara™
lumen extended longer for return blood and Gambro Dolphin Protect™ catheters; (B) Concept diagram of catheter lumen
B profiles used for dual lumen CRRT catheters.


via an artery and returning it to a vein, the term arterio- min for an adult CRRT circuit. Catheters are made with
venous (AV) is used. 75,76 In this system there is no mechan- different arrangement of the lumens revealing variation in
ical blood pump required, as the patient’s arterial blood their cross section profile (see Figure 18.15b) There is no
pressure provides a flow of blood in the EC. Veno-venous evidence to suggest which profile is better, but the larger
haemofiltration (CVVH) has the advantages of requiring the internal diameter, the less likely flow will be obstructed
only a single venipuncture, a reliable blood flow delivered during patient care with CRRT. After a catheter is threaded
from a blood pump, and alternative venous access sites if into a vein, the blood flow may be adequate, but later
77
site infection or access is difficult. While it is easy to during patient care it may obstruct due to different nursing
establish flow within AV-driven circuits and no complex interventions and patient movement, which may alter
system of blood pumps and pressure sensors is necessary, blood flows within the low pressure venous system. 70
this method is susceptible to flow problems associated
with low patient arterial blood pressure and high venous Insertion sites may be affected by nursing care interven-
pressures, a common occurrence in critically ill patients. tions. Placement of the catheter is usually in the subcla-
vian or femoral vein, and occasionally in the internal
78
The dual-lumen catheter used for veno-venous access has jugular vein. Anecdotally, the subclavian position is
an internal diameter of 1.5–3 mm and the ends of the more easily managed for dressing and securing, continu-
catheter are sufficiently separated from each other in the ous observation and patient comfort, but is more prob-
patient’s vein to prevent filtered blood from mixing with lematic in terms of flow reliability. Intrathoracic pressure
unfiltered blood when used in the recommended changes associated with physiotherapy or spontaneous
77
sequence. This ensures that filtered blood does not patient coughing and breathing, coupled with the upright
simply pass back through the artificial kidney, where there position of patients, may hinder blood flow from the
would be minimal waste clearance compared with ‘fresh’ subclavian-sited access catheter. While these issues are
unfiltered blood; this design is illustrated in Figure 18.15a. not encountered with a femoral-placed catheter, flow
The catheter must be small enough to place into a vein problems can arise due to side lying and flexion at the
but large enough to provide blood flow of at least 200 mL/ groin or hip. 42

Support of Renal Function 495


Blood-filled tubing fits inside outer housing and is compressed
by two cams to milk blood along, creating flow. Outer box housing of pump

Blood flow out of pump







Direction of rollers




Blood flow into pump




‘Cam’ of roller, which compresses
blood-filled tubing against outer housing
FIGURE 18.16 Roller pump for RRT.




The flow performance of any vascular-access catheter can
be affected by the patient’s position in bed, spontaneous Secondary IV line Syringe to adjust
movement and repositioning activities as part of routine Pressure sensing line blood level
nursing care in the critically ill for pressure-area preven-
tion. Catheter lumen outlet or inlet obstruction can be
due to contact with the vessel wall, or to a sharp bend
occurring due to the patient’s movement. These factors Air space and air–
blood interface
contribute to compromising blood flow in the EC, 42,77
and have been identified by ultrasound Doppler flow
probe attached to the circuit tubing. 79 Blood level
Blood Pump Direction of
In veno-venous modes, a pump component is essential blood flow
as part of the patient’s blood volume flows externally to
the body via the EC. Blood flow is maintained by a ‘roller
pump’ (see Figure 18.16), that propels the blood along
the tubing in a peristaltic fashion (milking along by com- Blood filter
pression of the tubing), compressing the blood-filled
tubing but having no contact with the blood itself. This
roller rotates at a rate providing a flow of fresh unfiltered
blood to the haemofilter, enabling it to clear metabolic
waste products.
The roller pump has a central anticlockwise rotating shaft FIGURE 18.17 Schematic of typical venous bubble trap design.
driving two roller wheels inside a rigid housing. Blood-
filled tubing sits stationary inside the housing and is
compressed by the outer surface of the roller wheels Venous Return Line Bubble Trap Chamber
during 180 degrees (half) of their rotation through the The purpose of this chamber is to prevent any gas bubbles
pump housing. This means that one of the two wheels is in the EC from entering the patient’s circulation by allow-
almost continuously compressing the tubing, moving ing them to rise to the top of a small, vertically positioned
blood forward out of the roller housing. The compression collection reservoir (see Figure 18.17). Venous pressure is
is not absolutely continuous, as there is a short time commonly measured via a tubing connection into the
(<0.5 sec) where there is no compression to allow the top of the venous chamber, and additional IV fluids can
tubing to refill with fresh blood. The compressed tubing be administered into this chamber via a secondary tube
reexpands behind the rotating roller and fills with fresh connection. The level of the blood in the chamber must
blood from the EC. be below the top, to prevent spillage into the pressure

496 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 18.3 Commonly used anti-clotting agents for CRRT

Drug Benefits Precautions
Heparin Inexpensive, wide experience, Sensitivity reactions, heparin-induced thrombocytopenia, to be effective means
easily reversed, easily increased risk of bleeding systemically
monitored, short half-life
Low-molecular-weight Moderately inexpensive, Difficult to monitor, not easily reversed, longer half-life, dosing varies between
heparin (LMWH) increasing experience, less likely types of LMWH
to result in sensitivity reactions
Prostacyclin Very short-acting, has a Expensive, no measure of effectiveness, narrow dose range with associated
physiological role in inhibiting hypotension, individual patients sensitive to haemodynamic effects, unstable
platelet activity, does not in solution
exacerbate other drug reactions
Citrate-based Limit anticlotting effect to EC – Substantial metabolic effect if not adequately managed (serum ionised calcium
solutions ‘Regional anticoagulation’; must be monitored closely); requires additions to extracorporeal circuit to
results suggest very effective in administer and reverse and use of specialised replacement/dialysate solutions.
prolonging circuit life Not useful when liver failure present, citrate is converted to bicarbonate by the
liver providing the necessary buffer for RRT. Acidosis may occur in liver failure
No anti-clotting agent No side effects, no exacerbation of May encounter very short circuit life that consumes remaining haematological
(with saline flushes) unstable haematological status, components, risk of fluid overload if saline flushes not part of fluid balance.
liver failure No evidence saline flushes have any benefit



monitoring line. It is advised that the blood level be visual inspection for clotting in the EC is undertaken,
adjusted to near full but allow for visual inspection of particularly noting the venous bubble trap.
incoming blood flow and to ensure that any air bubbles
69
are trapped here. As this creates a gas–blood interface Citrate is another popular anticoagulant for CRRT as an
within the venous chamber there is a potential source of alternative to heparin. Citrate buffers pH and chelates
venous chamber clotting and hence circuit failure. 42,69,80 calcium inducing anticoagulation of blood by reducing
Addition of replacement fluids into this chamber when serum ionised calcium level. For anticoagulation, the
using post-dilution fluid administration can cause a dose and dose rate of citrate is commonly set to achieve
plasma fluid layer to develop above the blood level and a reduction in the CRRT circuit blood ionised calcium
87-89
may reduce clotting by stopping blood foaming on its level to <0.3 mmol/L. As ionised calcium is essential
surface and eliminates air or gas contact with the blood. 81 for the progression of the coagulation cascade to form a
stable clot, an anticoagulant effect is achieved when the
Anticoagulation calcium is bound or chelated. A continuous infusion of
88
There are several different drugs utilised to prevent blood citrate is administered into the CRRT circuit, as patient
clotting in the EC; heparin, prostacyclin and sodium citrate blood enters the circuit similar to heparin administra-
have been used separately or in various combinations (see tion. A new approach in Australia includes citrate as an
Table 18.3). 82-84 As blood comes into contact with the additive to commercially-prepared CRRT replacement
90
plastic tubing and the polymer fibres of the filter, various fluids. When circuit blood returns to the patient circula-
clotting systems are activated. This is a normal action of tion, it mixes with systemic blood and the calcium con-
blood when exposed to non-biological surfaces. The aim centration is restored to normal; free citrate not binding
of anti-clotting drugs is to delay clot formation while the to calcium is metabolised by the liver to provide carbon
87-89
blood is outside the body, particularly when within the dioxide and bicarbonate as a necessary buffer.
densely-packed fibres of the filter. As calcium, blood plate- However, citrate-bound calcium is lost in the waste fluid
80
let cells or thrombin are vital in clot formation, these removed and requires replacement by a separate calcium
drugs are targeted to one of these elements. This targeting infusion to maintain serum calcium levels to normal; at
87
must not be too pronounced, as the patient may begin to 1.0–1.3 mmol/L. With this method, the circuit is anti-
bleed when the blood returns from the EC to the body. 80 coagulated, but the patient is not (also called a ‘regional’
method of anticoagulation) as the patient blood calcium
Heparin is the most commonly-used agent for the level is restored to normal making this approach safer
prevention of clotting, as it is inexpensive, widely avail- compared to heparin use and can be applied in auto-
82
able and easily reversed by another drug, protamine. anticoagulated patients where premature circuit clotting
91
Heparin is commonly administered into the EC before continues to occur. Due to the complex nature of the
the blood enters the filter, although the optimal place to citrate-based anticoagulation approach a number of dif-
administer any anticoagulant drug during CRRT is not ferent protocols have been proposed to aid in manage-
92
agreed upon. 85,86 A bolus is often given prior to circuit ment. Not all methods will be applied in the one ICU,
connection, either in the circuit prime or via the venous and local expertise development of one method and an
access catheter. A maintenance dose (5–15 units/kg/h) is alternative is common. Recent reviews provide a good
then adjusted against the relevant laboratory tests and a synopsis of each method. 93

Support of Renal Function 497

Normal clotting time, a laboratory test designed to production from tapwater at the bedside. This approach
measure the time taken for blood to clot under laboratory can be cheaper, requires no bag changing or reconstitut-
98
conditions, is used as a reference to determine a suitable ing by nurses, but involves installation of a complex and
therapeutic range of the anti-clotting drug during CRRT. expensive reverse osmosis machine, the cost of which
Different tests are applicable to different medications and would be offset if large volumes of fluid were then con-
their site of action in the clotting cascade. When using sumed from this online manufacture. This approach may
any anti-clotting agent, a balance is required between the alter fluid selection and use in the future, and is an essen-
benefits of increased coagulation suppression and the tial feature of chronic dialysis and use of ICU daily dialy-
higher risk of patient systemic bleeding. In each patient sis (EDDf) modes of therapy. 59-61
this risk may vary, depending on illness, accompanying Fluid balance maintenance is a key nursing responsibility
liver failure and administration of concurrent anti-clotting in managing CRRT. Most machines now available to
agents such as activated protein C.
provide CRRT incorporate a mode selection program,
Fluids and Fluid Balance including an automatic fluid balance system. This ensures

A key component of any CRRT is the administration of a delivery of a fluid prescription based on the input pro-
vided by the programming nurse. As many litres of fluid
replacement solution for the fluid removed during hae- may be exchanged in an hour (25–35 mL/kg), the default
mofiltration (see Table 18.4). This same physiologically setting is usually a net machine balance, where all fluids
balanced solution is also used as a dialysis fluid if a dialytic administered as either dialysate or replacement are recov-
mode is included. The solution may have a low potassium ered or balanced. The machine cannot, however, include
level, so this electrolyte can be removed rapidly if hyper- fluids administered or expelled directly from the patient,
kalaemia is part of the original indication for CRRT. Potas- so a fluid maintenance schedule must be established.
sium must therefore be added later to the solution to This schedule is also based on input and output being
ensure that hypokalaemia does not occur. In Australia and equal. For example, if more fluid is being infused into the
New Zealand these fluids are commercially prepared, with patient than being lost, as would be expected in ARF, then
the only major choice being between the type of acid additional fluid would need to be recovered via the CRRT
buffer: lactate or bicarbonate. Some small studies have circuit: that is, less replacement fluid administered or
compared the use of lactate and bicarbonate fluid buffer more waste created. Consider the calculation steps in the
because of a concern that the lactate solution reduced example in Table 18.5.
heart performance by causing cardiovascular depression
and made accurate determination of patient lactic acid Irrespective of the accuracy of fluid replacement assess-
accumulation difficult to interpret. 94-97 In most settings the ment prior to therapy, individual patient assessment for
use of lactate-buffered fluids in patients with cardiac and fluid status must occur at least twice a day. Subtle tem-
liver failure is avoided, as lactate accumulation (levels perature changes in the patient, fluid boluses, diarrhoea
above 5 mmol/L) in these patients indicates inadequate and variable absorption of feed may all contribute fluid
metabolism of lactate to bicarbonate by the liver, with losses not included in routine fluid maintenance. As treat-
13
increased acidaemia. While bicarbonate solutions may ment progresses over time, this may exacerbate a general
appear to have an advantage over lactate-based solutions
in critically ill patients, they are more expensive causing
some physicians to only prescribe them when lactate accu-
mulation is anticipated or after it occurs. TABLE 18.5 Example of CVVH fluid maintenance
schedule to calculate replacement solution dose/hour
The higher cost, problems with reconstituting bicarbon-
ate solution bags and manual handling of large (5 L) Fluids in (mL) Fluids out (mL) Fluid balance (mL)
fluid bags has increased interest in ‘online’ fluid
1. Drugs, IV, NG 2. drains = 10 mL/h + 85 mL (+ve
= 120 mL/h insensible losses = balance/h)
(heparin, 25 mL/h
inotropes,
TABLE 18.4 Typical replacement/dialysate fluid intraflows, NG
feeds)
constituents for CRRT
3. CVVH fluid removal
Bicarbonate-based Lactate-based dose = 2500 mL/h
Component solution (mmol/L) solution (mmol/L) (25–35 mL/kg/h)
4. Total in = 5. Total out = 35 mL/h
Buffer 25.00 45.00 120 mL/h (from 2) + 2500 mL
Potassium 0.00 1.00 ultrafiltrate =
2535 mL
Sodium 140.00 140.00
6. Patient overloaded 7. Replacement
Glucose 0.00 10.00 on clinical solution/h = 2535
examination; need (−120 mL fluid
Calcium 1.63 1.63 to remove an input; −25 mL to
Magnesium 0.75 0.75 additional 25 mL/h reduce fluid
overload) =
Chloride 100.75 100.75 2390 mL/h

498 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 18.6 Comparison of CRRT and IHD

Factors CRRT IHD
Blood pressure Less instability because of lower blood and Removal of large volumes of fluid in a short
stability dialysate flow rates and the continuous nature time frame, causing hypotension and
of the treatment with slower fluid removal rate blood pressure instability during treatment
Waste clearance Control of urea and creatinine (key wastes) Peaks and troughs of urea and creatinine
achieved slowly and steadily; critical in associated with daily or second daily
managing patients with intracranial pathologies treatments
Nutritional support Larger volumes of nutritional fluid can be Continuous feeding difficult because of fluid
administered with concurrent clearance of volume requirement and accumulation
products of protein digestion and fluid load while off treatment
Electrolyte, acid–base Ability to adjust dose of treatment and Potential acute changes in pH during
and body water replacement of electrolytes, acid–base balance treatment; acid and electrolyte
homeostasis and body water balance to meet patient needs accumulation while off treatment
as necessary
Neurotrauma and Fare much better when managed by CRRT Fluid shifts can aggravate cerebral oedema
surgery patients without acute changes in solute levels such as and be life-threatening; IHD
urea and sodium contraindicated for patients with raised ICP
Sepsis or severe Blood-borne mediators in sepsis and Diffusive and intermittent process in IHD not
infections inflammatory illness (cytokines) better removed as effective at removing the mediators of
by the convective process in CRRT (CVVH) inflammation due to molecular size


loss of body fluid and dehydrate the patient. Regular to initiate treatment may result in patients developing a
weighing of patients may assist in assessing this situation. worsening acidosis, higher potassium and urea levels,
Electrolyte disturbances may also occur despite use of reduced or no nutritional intake and oedema with heart
88
balanced replacement solutions. Particular attention failure. This suggests that prescribing IHD and using the
should focus on regular assessment of fluid and electro- limited resources of dialysis nurses for a service to the
lytes, especially potassium, sodium, phosphate and mag- ICU is inefficient, resulting in patients deteriorating
nesium levels (see Chapter 19). further before treatment. As the IHD treatment may also
be poorly tolerated when started and then seen as less
PROPOSED BENEFITS OF CRRT AND ‘well tolerated’ when delay has created less stable patients,
COMPARISONS WITH IHD this can be avoided by the prompt initiation of CRRT.
As a continuous therapy, CRRT is considered a better Depending on nursing organisational structures, CRRT
33
therapy than IHD for critically ill patients for a number can be cheaper in the ICU, where one nurse cares for the
of reasons (see Table 18.6). Critically ill patients are often critically ill patient and the CRRT. This is a primary argu-
haemodynamically unstable and tolerate large fluid shifts ment supporting CRRT in the Australian and New Zealand
42
poorly (see Chapter 20). The CRRT approach may be context, where an IHD treatment means two nursing
better at improving blood pressure stability than IHD. It salaries are apportioned to one patient for the period of
has also been proposed that CRRT may be beneficial to treatment in the ICU. There are mixed models, where a
patients with severe sepsis through the continuous clear- dialysis nurse initiates and terminates a treatment, leaving
ance of inflammatory mediators, which are linked to the the ICU nurse to manage the machine and treatment for
70
systemic inflammatory response syndrome. Despite this, the time in between. Comparison of approaches is,
CRRT alone may not be of any benefit to this condition, however, difficult because of variable staffing and system
as many mediators in sepsis are not cleared via convec- structures in different countries. What little evidence is
tion and antiinflammatory mediators may also be available suggests that cost differences between CRRT and
51
removed, which may have a counter effect to the pro- IHD are minimal, however this depends on how this is
inflammatory mediator removal. 91 calculated and what the costing includes, and reports
highlight a great deal of variation between centres and
The continuous nature of fluid removal and replacement 99
in CRRT facilitates fluid management and the administra- countries for items included.
tion of nutrition, either enterally or parenterally. This is
in contrast to the intermittent profile of fluid removal to CONTINUOUS RENAL REPLACEMENT
a point of relative hypovolaemia at treatment end, to MACHINES
relative hypervolaemia at treatment commencement seen
with the use of IHD, even on a daily schedule. There are many machines available for CRRT in the ICU.
Identifying the machine that a particular ICU should use
The efficiency in initiation and application, the nursing or purchase is a common question from nurses, and there
workload and costs of the two approaches are also impor- is limited literature available to guide this decision,
tant considerations. Delays in waiting for dialysis nurses however recent literature provides some comparisons of

Support of Renal Function 499



TABLE 18.7 Machine design and build approaches

Machine type Waste collection Membrane Circuit Pressure measurement Priming preparation
A One 5 L bag, empty AN69, prefitted, not Cartridge kit-based, In-line pressure Fully automated
when full, change changeable multipurpose; all transducers
bag modes
B 1–4 bags or 20 L Infomed Membrane Single tubing Isolated sideline air Semiautomated
bottle with pump not fitted, option components interface transducers
to drain direct: no for other partly assembled,
waste handling membranes mode specific










































FIGURE 18.18 The Prismaflex CRRT machine (Hospal, Lyon, France).

100
their technical characteristics. Table 18.7 outlines the
major differences in machines or system approaches. Two
machines adopting common design features from Table FIGURE 18.19 The Infomed HF 440 CRRT machine (Infomed, Geneva,
18.7 are shown in Figures 18.18 (Prismaflex; Hospal, Switzerland).
Lyon, France) and 18.19 (Infomed HF 440; Infomed,
Geneva, Switzerland), each highlighting the major tech- often used. This was an adaptive technology and
42
nical differences in how CRRT machines are presented required a very manual, idiosyncratic approach. These
and used. days, with automated technology and on-screen prompts
and sequential step-by-step diagrams on machine screen
NURSING PRACTICE displays, such policies are not required, and the key head-
Key nursing management themes found in the literature ings in Table 18.8 along with the key nursing themes
useful for application of CRRT are: education and train- above, are a roadmap for protocol development. Table
ing; 42,101,102 methods for fluids management and fluid 18.8 also provides a brief problem and intervention-
92
balance; 103,104 anticoagulation approaches; and machines based review of nursing management for CRRT. For each
used. 99,100,105 Nursing protocols developed in the early group of nursing interventions, a practice recommenda-
1980s focused on how to prepare and prime a CRRT tion is included. These recommendations could be the
system, as modified dialysis pumps with IV pumps were framework for a nursing standard or policy for CRRT. A

500 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 18.8 Troubleshooting guide

Nursing area Potential problem Key nursing interventions required
Patient and 1. Machine alarms and 1. Machine test and/or checklist completed
machine/system technical failure on 2. Double-check all line connections around circuit
preparation starting treatment 3. Treatment orders cross-checked with settings
before use 2. Air entrainment 4. Double-check fluids used, e.g. any additives required
3. Fluid setting errors Recommendation: patient in bed, supine position and MAP >70, stable.
4. Fluids/electrolytes
incorrect
Connection to the 1. Access catheter 1. Prep access connections with antiseptic and test flush return (venous) lumen and
system and obstruction/failure aspirate outflow (arterial) lumen
initiation of 2. Hypotension 2. Connect both circuit lines to access catheter administering priming volume to patient
therapy a. Increase vasoactive drugs first to maintain MAP
b. Start blood pump slowly with small increases until blood fills all of the circuit
Recommendation: use two nurses for connection routine. Start fluid replacement and
removal only after blood circuit is full and at prescribed speed.
In-use 1. Low pressure: 1. Maintain access catheter alignment, preventing kinks
troubleshooting ‘arterial alarm’ 2. Do not place extra connections or taps between access catheter and circuit lines
and 2. High pressure: 3. Blood pump speed >150 mL/min
maintenance, ‘venous alarm’ 4. Ensure venous chamber filled well above air sensor, bubbles removed
particularly fluid 3. High TMP alarm 5. Heater set to 37°C
balance 4. Air detected alarm 6. Use fluids chart or similar to account for all fluids used including anticoagulant
5. Hypothermia 7. Potassium additive to CRRT fluid is often required after 24–48 hours of treatment;
6. Fluid balance errors some patients are hypokalaemic despite acute renal failure
7. Electrolyte Recommendation: assess and reset fluid balance settings hourly, particularly in unstable
imbalance patients and for inexperienced staff.
Monitoring and 1. Premature clotting 1. Check and monitor effect of anticoagulant therapy after first 6 hours and then daily
adjustment to in circuit and filter a. Maintain adequate dose to therapeutic range
anticoagulation b. Use predilution fluid administration
c. Use blood flow greater than 150 mL/min
d. Use large-bore access catheter and take care not to obstruct catheter
e. Keep blood pump operating: minimise stops >30 sec
Recommendation: if frequent failure, always check for blood flow obstruction before more
anticoagulation; e.g. request change or replacement access catheter if obstructed.
Access care and 1. Access 1. Ensure catheter sutured in place and well secured with dressing
dressings dislodgement 2. Use asepsis when flushing or connecting to access catheter; monitor site for infection
2. Access catheter 3. Use heparin to fill catheter deadspace when not is use for >4 hours
infection Recommendation: use flexible dressing with application to both sides along catheter
3. Access catheter allowing movement away from skin surface, preventing obstruction during patient
obstruction care/positioning.
Vital sign 1. Arrhythmias, 1. Monitor vital signs hourly, consider any link between changes and use of RRT; e.g. low
monitoring hypotension, fever CVP and inadvertent fluid loss occurring
Recommendation: CVP readings should be performed 2–4-hourly during CRRT; CVP can be
used as a target for daily fluid loss prescription.
Assessment of 1. Filter clotting 1. If transmembrane pressure (TMP) or prefilter pressure (P-IN) >250 mmHg, consider
filter function abruptly with electively returning blood by saline infusion into circuit and ceasing treatment
and patency inability to return a. Observe for venous chamber clot development. If excessive and venous pressure
circuit blood to the >200 mmHg, consider electively returning blood by saline infusion into circuit and
patient ceasing treatment
2. Inadequate solute 2. Assess patient’s urea and creatinine measures; they should be reducing or stable
removal Recommendation: blood flow into venous chamber should be visible, i.e. not full; to
identify clot, reduce level of blood to detect clot and/or perform a small saline flush
(~100 mL) into circuit to check for clot formation.
Cessation of 1. Blockage and/or 1. Use concentrated heparin to fill deadspace of catheter when not in use >4 hours. Use
treatment and clotting in access 1000 IU/mL and follow manufacturer’s specifications for volume required
disconnection catheter 2. Always cease a circuit before it clots, return patient blood
from the 2. Inadvertent blood 3. Use asepsis for disconnection procedure
extracorporeal loss Recommendation: access catheter should not be used for other purposes/infusions when
circuit 3. Infectious risk RRT is not connected.
Temporary 1. Maintenance of 1. Flush out any excess blood residue in circuit, keep blood pump operational with saline
disconnection circuit before in circuit
for procedures reconnection 2. Circuits in use for >24 hours before disconnection or not restarted after 6 hours
2. Infection following temporary disconnection, consider discarding
3. Inadvertent fluid 3. After restarting circuit, increase fluid loss to remove fluid used to re-establish RRT
administration Recommendation: add heparin 5000 IU to circuit when temporarily disconnected, but
flush this out with 200–300 mL saline before reconnection; always use additive label for
this procedure.

Support of Renal Function 501

number of publications provide clinically-focused out- understanding of how the kidneys function and indeed
lines of nursing management for the CRRT technique and fail at a cellular level is continuing to evolve. There are a
patient care. 54,106 Additional information for the specific variety of illnesses and clinical events that result in acute
equipment and products used by an individual ICU are renal failure. An artificial process is able to achieve kidney
also necessary. This would include components such as function and replacement, and in the acute setting this is
size and type of membranes used, access catheters, fluids achieved with CRRT, different from that used in chronic
(bicarbonate and lactate) and additives. cases. There are several options for this support process in
the ICU, and much of what is done evolved out of dialysis
SUMMARY developments that originated in the 1940s. Nursing man-
agement of these therapies is an exciting and important
Acute renal failure is a common complication associated role for the intensive care nurse, with limited evidence to
with critical illness. The human kidneys may appear to guide practice. This chapter, outlining renal physiology,
perform simple functions of blood filtration or cleansing, pathology, illness and disease with the development and
but they are complex organs with additional functions use of the artificial kidney, aims to encourage nurses to
related to the endocrine and immune systems. An further develop this area of nursing practice in the ICU.



Case study
Andrew Citizen, a 36-year-old man, 180 cm in height and weighing tense and swollen. The surgeon insisted on a CT scan to further
112 kg, was admitted to the ICU from a regional hospital 36 hours assess the abdomen. After some discussion it was finally agreed
after undergoing a laparoscopic cholecystectomy, then a subse- and arranged for 2 hours later. The CVVHDf was ceased and
quent laparotomy and closure of a bowel perforation and leaking Mr Citizen was prepared for transport. During the CT, his condition
bile duct 18 hours later. Since this procedure he had complained deteriorated; he became febrile, required increasing inotropes to
of increasing abdominal pain, rigidity and guarding, fever up to maintain his BP, and his FiO 2 was increased. His conscious state
39.4°C, elevated WCC, increasing difficulty breathing, restlessness appeared to also deteriorate, although this was hard to assess as
and confusion. His urine output had dropped below 0.5 mL/kg/h he was sedated for transport. Large intra-abdominal fluid collec-
for several hours. tions were noted on the CT. The surgeon was keen to re-explore
the abdomen, but ICU staff remained concerned about Mr Citizen’s
On admission to the ICU, he was intubated and ventilated (stan-
dard procedure for the Royal Flying Doctor Service transport of unstable condition. CVVHDf recommenced, and Mr Citizen again
the critically ill), warm, tachycardic (124 beats/min), hypotensive improved after some hours.
(85/50 mmHg), heavily sedated and unresponsive to commands, Mr Citizen remained stable 48 hours later, on SIMV FiO 2 0.4, 5 cm
and oliguric. Given the history and presenting symptoms, he was PEEP, mildly febrile, low-dose noradrenaline, haemodynamics con-
diagnosed with postprocedural sepsis secondary to bowel perfora- sistent but mildly elevated. It was decided to electively cease CRRT
tion. He was acidotic (pH 7.29) with a lactate of 3.5 mmol/L, uraemic and insert a urinary catheter to assess renal function.
(13.5 mmol/L), and had a creatinine level of 205 mmol/L. Mr Citizen’s condition remained reasonably stable, although oligu-
After initial assessment the following therapy was prescribed: ria persisted and his temperature again rose. It was agreed that the
● broad-spectrum antibiotic cover; already commenced but patient should return to theatre to drain fluid accumulations 12
adjusted hours after stopping the infusion.
● continuing ventilatory support, lightening sedation to better On return from theatre, Mr Citizen was again haemodynamically
assess neurological status unstable, hypothermic and anuric. Fluid challenges were ordered,
● change of CVC line, insertion of PA catheter and arterial line, inotropes increased and CVVHDf recommenced on the previous
and assessment of cardiac output and haemodynamic profile regimen. The patient staged a minor recovery, but early in the
● administration of boluses of 0.9% saline to restore circulating treatment cycle, intermittent flow difficulties were experienced
fluid deficit from the subclavian vascath, and 4 hours later the circuit clotted.
● commencing noradrenaline infusion at low dose until haemo-
dynamic profile improved A new femoral vascath was inserted, CRRT was recommenced
● surgical consult with a heparin infusion at 8 U/kg/h. The patient was stabilised
● commencing CVVHDf if no response to fluid and inotropes post procedure. He was weaned from inotropes over the next 24
● blood cultures. hours and moved onto CPAP. His urine output returned over the
next 2 days, with the CRRT circuits clotting approximately every
Mr Citizen’s oliguria persisted despite restoration of a satisfactory 24 hours.
MAP with inotropes and fluid administration, and his serum creati-
nine levels continued to rise. CVVHDf was started at 30 mL/kg/hr With a return of urine function and output at 0.5 mL/kg, and failure
with predilution fluid replacement. No anticoagulant was adminis- of the next circuit due to clotting, CRRT was not recommenced.
tered. Two hours later, the patient’s temperature fell to 37.8°C, hae- Fluids were restricted and recovery occurred over the next days.
modynamics improved and the FiO 2 could be weaned from 0.8 to Mr Citizen’s urea level fell from a high of 19.9 mmol/L to
0.6 over the next 6 hours, and PEEP decreased to 5 cmH 2 O. 11.5 mmol/L, his creatinine returned to 150 mmol/L and he was
now experiencing post-ARF polyuria in excess of 100 mL/h. His
Mr Citizen’s conscious state improved, and his condition continued condition continued to improve and he was discharged from ICU
to stabilise over the next 12 hours, although his abdomen remained 24 hours later.

502 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



Research vignette
Bagshaw SM, Laupland KB, Boiteau PJ, Godinez-Luna T. Is regional data, along with details of the CRRT filter start and stop times, type
citrate superior to systemic heparin anticoagulation for continuous of anticoagulation and complications, were obtained. The study
renal replacement therapy? A prospective observational study in describes in detail the protocol for anticoagulation with both sys-
an adult regional critical care system. Journal of Critical Care 2005; temic heparin and regional citrate. This protocol had been imple-
20: 155–61. mented for approximately 3 years prior to the study, so the staff
involved have considerable experience using this protocol. All
Abstract patients received CRRT by the same CRRT machine. By protocol,
Purpose CVVH was the only modality used with systemic heparin, whereas
Continuous renal replacement therapy (CRRT) is commonly used for regional citrate the only modality was CVVHDf.
in the care of critically ill patients, although the optimal means of
anticoagulation is not well defined. We report on our regional CRRT The primary outcome measure was filter circuit lifespan (hours).
protocol that was developed using the principles of quality The difference in filter circuit lifespan between systemic heparin
improvement and compare the effect of regional citrate with sys- and regional citrate anticoagulation was analysed using the non-
temic heparin anticoagulation on filter lifespan. parametric Mann–Whitney U test, reported as median (interquar-
tile range) and Kaplan–Meier survival time. There were 212 filters
Materials and methods assessed in the citrate group and 97 in the heparin group. The
Prospective observational cohort study in a Canadian adult median time to failure was 40 hours and 20 hours for citrate and
regional critical care system. A standardised protocol for CRRT has heparin respectively. Further analysis considered the proportion of
been implemented at all adult intensive care units in the Calgary filter circuits reaching a lifespan >72 and <24 hours. The reasons
Health Region since August 1999. All patients with acute renal for filter circuit failure or discontinuation were also reported for
failure treated with CRRT during 1 October 2002 to 30 September 11,427 hours of CRRT. Several previous studies were reviewed and
2003, were identified and followed up prospectively until hospital compared with the findings of this study in a discussion highlight-
discharge or death. ing some very important points.

Results The evidence from this study favours the use of regional citrate as
Eighty-seven patients with acute renal failure requiring CRRT were the primary anticoagulant during CRRT; however, the authors
identified, 54 were initially treated with citrate, 29 with heparin, suggest that further study is warranted in the form of a randomised
and 4 with saline flushes. Citrate and heparin were used in 212 clinical trial. This study also suggests that the use of citrate may
(66%) and 97 (30%) of filters for 8776 and 2651 hours of CRRT, result in fewer bleeding episodes and the need for transfusions due
respectively. Overall median (interquartile range) filter lifespan to more reliable filter circuit lifespan, and a reduced time off CRRT.
with citrate was significantly greater than heparin (40 [14–72] vs 20 The implications for this are decreased nursing workload; however,
[5–44] hours, P < 0.001). Citrate anticoagulation resulted in greater the authors did not collect data specifically on these outcomes.
completion of scheduled filter life span (59% vs 10%, P < 0.001).
Citrate anticoagulation was well tolerated with no patient requir- While not a randomised comparison of systemic heparin and
ing elective discontinuation for hypernatraemia, metabolic alkalo- regional citrate anticoagulation, this study does have a few
sis, or hypocalcaemia. strengths. Specifically, it included patients from several centres in
which this protocol is used, and assessed a large total number of
Conclusions filter circuits. However, the study does have limitations. One pos-
Regional citrate anticoagulation was associated with prolonged sible weakness of an observational study is the inability to control
filter survival and increased completion of scheduled filter lifespan for ‘other’ confounding factors influencing filter lifespan, such as
compared with heparin. These data support small studies suggest- the CRRT modality or type and position of vascular access catheter
ing that citrate is a superior anticoagulant for CRRT and suggest where blood flow failure may have occurred. In addition, the study
the need for a future definitive randomised controlled trial. did not incorporate data on individual filter transmembrane pres-
sure (TMP) and selected patient-related factors (e.g. haematocrit,
Critique activated partial thromboplastin time). Finally, it did not integrate
This study was conducted in a single health region in Canada potentially important outcomes, such as clinically relevant throm-
(population ~1 million) where a standardised CRRT protocol for bocytopenia, bleeding episodes, need for blood product transfu-
management of ARF has been implemented. In a prospective sion or overall cost.
observational cohort design, patients were provided with either
systemic heparin or regional citrate anticoagulation during CRRT, Overall, this study is an important contribution to understanding
and filter circuit ‘lifespan’ was compared. Data were collected from methods for anticoagulation during CRRT, is useful reading and is
three adult multidisciplinary ICUs between October 2002 and very relevant to complement the information provided in this
September 2003. Patient demographic, clinical and laboratory chapter.

Support of Renal Function 503



Learning activities
Learning activities 1–4 relate to the Case study. 3. Construct a simple dot-point checklist of the machine and RRT
1. Construct a database for your ICU to collect the filter ‘life’ for circuit before connecting to the patient. The list should be no
CRRT using a common spreadsheet program (e.g. Microsoft longer than one page and should include machine power,
Excel). Include in this database: tubing connections, fluid balance, anticoagulation and alarms.
● the RRT circuit start and stop time If such a list or check routine exists, does it need modifying or
● the reason the RRT failed or was stopped updating?
● effective use time before clotting or ceasing 4. All staff enjoy case presentations. Review a patient throughout
● the type and dose of anticoagulation used his/her illness when treated with RRT, and construct a case
● the patient’s daily clotting results presentation. Even if the case is routine, it may be useful to
● the daily urea and creatinine results. compare and contrast with a problematic case. Include in the
From this database, determine the mean, median and range of case: medical history, diagnosis and ARF presentation, bio-
filter life. This is an important measure, as the median value is less chemistry and diagnostic test results. Include initiation of RRT,
influenced by outliers or data that are well outside the ‘average’.
The ‘mean’ filter life may be changed significantly if one filter life solute levels, effective treatment time, problems, successes
was 100 hours when most of them were 22 hours, for example. and outcomes. What could be improved for another patient
Relationships or correlations can then be made between filter life treatment?
and anticoagulation used and clotting indices. In addition, it is 5. Create a learning resource for staff caring for a patient during
possible to determine the time spent off the CRRT, and this can be
a measure of nursing expertise resetting the circuit and/or reflect RRT, for example, a ‘tips and tricks’ list to aid new users and also
delays when medical staff need to attend to the patient before the to ensure efficiency and safety. What are the most common
new circuit can begin. problems or errors when using your RRT in the ICU? List these
2. Compare data from two facilities that use a different method and devise a guide for their prevention and/or remedy.
or machine (e.g. anticoagulation). Locate a friend or colleague
from a different ICU, collect data and then compare.




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56(Suppl 72): s32–6. 106. Baldwin I, Fealy N. Clinical nursing for the application of renal replacement
97. Thomas AN, Guy JM, Kishen R, Geraghty IF, Bowles BJM, Vadgama P. Com- therapies in the Intensive Care Unit. Seminars in Dialysis 2009: 22(2):
parison of lactate and bicarbonate buffered haemofiltration fluids: use in 189–93.
critically ill patients. Nephrol Dial Transplant 1997; 12(6): 1212–17. 107. Phipps W, Monahan F, Sands J et al. Medical-surgical nursing, 7th edn.
98. Bellomo R, Baldwin I, Fealy N. Prolonged intermittent renal replacement St Louis: Mosby; 2003.
therapy in the intensive care unit. Crit Care Resusc 2002; 4: 281–90. 108. Mader S. Inquiry into Life, 11th edn. New York: McGraw-Hill; 2006.
99. Nattachai S, Lawsin L, Uchino S, Bellomo R, Kellum JA, BEST kidney Inves-
tigators. Cost of acute renal replacement therapy in the intensive care unit:

19 Gastrointestinal, Liver and

Nutritional Alterations





Andrea Marshall
Teresa Williams
Christopher Gordon





INTRODUCTION
Learning objectives
During episodes of critical illness, patients often experi-
ence disturbance in their metabolic and/or endocrine
After reading this chapter, you should be able to: function. The gastrointestinal system and the associated
● describe the changes in normal gastrointestinal physiology splanchnic circulation may be compromised without
and metabolism associated with critical illness overt signs being evident. This alteration in regional
● integrate theoretical knowledge of the nutritional blood flow and tissue oxygen delivery can compromise
requirements, assessment of and potential for malnutrition normal metabolic and endocrine function. In this chapter
in the critically ill with clinical practice and rationalise the effect of gastrointestinal physiology on critical illness
selected nutritional support strategies for specific patients is provided. Second, nutritional requirements and support
● identify patients at risk for the development of stress ulcers strategies for critically ill patients are described. Third,
and rationalise therapeutic interventions for their complications associated with the stress, including the
prevention development of stress-related mucosal diseases, are dis-
● discuss the effects of critical illness on hepatic function and cussed. Fourth, assessment and management of liver
evaluate the consequences of liver dysfunction dysfunction, including liver transplantation, is reviewed.
● describe the treatment of liver failure, including liver Finally, hyperglycaemia in critical illness, the role of gly-
support therapies and transplantation caemic control and the assessment and management of
● critically analyse the role of glycaemic control in the context diabetic ketoacidosis is addressed.
of critical illness
● describe the physiological changes that occur during GASTROINTENSTINAL PHYSIOLOGY
diabetic ketoacidosis and rationalise assessment and
treatment strategies. Digestion and absorption of nutrients such as carbohy-
drates, amino acids, minerals and water are key functions
of the gastrointestinal system. Digestive enzymes are
responsible for breaking down food into smaller sub-
stances that can be absorbed by the gastrointestinal tract.
While some digestion begins in the oral cavity (for
Key words example, the breakdown of starch into sugar by salivary
amylase), the stomach, pancreas, and small intestine
secrete the most enzymes responsible for digestion (Table
anabolism 19.1). The small bowel plays an important part in the
catabolism digestion and absorption of these nutrients, where the
hypermetabolism processes of diffusion, facilitated diffusion, osmosis and
enteral nutrition active transport are responsible for absorption of 90%
total parenteral nutrition of all nutrients. The remaining 10% of nutrients are
1
glycaemic control absorbed in the large intestine.
diabetic ketoacidosis The secretion of enzymes and absorption of these small
liver failure molecules produced during digestion is an energy-
hepatic encephalopathy consuming process that can be negatively influenced by
hepatorenal syndrome gastrointestinal hypoperfusion and the failure of the gas-
extracorporeal liver support trointestinal tract to receive sufficient oxygen and nutri-
506 tients required for cellular function.

Gastrointestinal, Liver and Nutritional Alterations 507

was described in relation to symptoms, such as gastro-
TABLE 19.1 Enzymes required for digestion intestinal bleeding, mechanical obstruction, and pancre-
17
18
of nutrients 2 atitis resulting from ischaemia. However, the presence
of covert ischaemia has resulted in a heightened interest
Location Enzymes Target substance in the prevention and early detection of gastrointestinal
ischaemia in the critically ill, in an attempt to minimise
Oral cavity Salivary amylase Starch and
(ptyalin) glycogen ischaemia-related dysfunction.
Bromelain Protein
Stomach Pepsin Proteins Gastrointestinal Mucosal Hypoperfusion
Gelatinase Proteoglycans in The gastrointestinal system is particularly susceptible to
meat (gelatine
and collagen) alterations in regional blood flow and oxygen delivery
Gastric amylase Starch because it has a higher critical oxygen delivery (DO 2 )
Gastric lipase Triglyceride than the rest of the body. Splanchnic vasoconstriction is
Chymosin Milk also proportionally greater than other vascular beds and
Pancreas Trypsin, Proteins the countercurrent O 2 exchange between vessels within
chymotrypsin, the villi further contribute to decreased regional oxygen
carboxypeptidase, delivery. 5
elasatases
Pancreatic lipase Triglycerides During shock states, decreased blood flow from vasocon-
Pancreatic amylase Carbohydrates striction occurs in this region first. It is the last place to
19
be restored following successful resuscitation. In shock
Small intestine Sucrase Sucrose states, the gastrointestinal system attempts to maintain
Lactase Lactose
Maltase Maltose (into 2 adequate cellular oxygenation by increasing the amount
molecules of of oxygen extracted from the blood. This increase in
glucose) oxygen extraction may prevent serious compromise of
Isomaltase Maltose into tissue oxygenation even in the presence of reduced oxygen
isomaltose delivery. 20
Intestinal lipase Fatty acid


Practice tip
The gastrointestinal tract also plays a role in immunity. It Remember, assessment of arterial blood pressure, heart rate
has a variety of mechanisms in place that prevent the and urine output provides information about the haemody-
movement of substances (other than nutrients, water and namic and oxygenation status of the whole body. A reduction
electrolytes) into the systemic circulation (see Table 19.2). in regional perfusion and oxygenation may occur despite con-
In the setting of critical illness, where gastrointestinal ventional clinical assessment findings being normal.
hypoperfusion may be present, these protective functions
may be diminished, so it is essential to understand the
alterations in normal gastrointestinal physiology that During periods of ischaemia and hypoxia, oxygen free-
occur during critical illness. radicals are generated as byproducts of anaerobic meta-
bolism. With successful resuscitation of the gastrointestinal
tract, blood flow and oxygen delivery are restored but the
ALTERATIONS TO NORMAL oxygen free-radicals are liberated, contributing to the
GASTROINTESTINAL PHYSIOLOGY IN microvascular and mucosal changes characteristic of isch-
CRITICAL ILLNESS aemia and reperfusion of the gut mucosa. 21
During critical illness, the digestion and absorption of
nutrients may be altered. Gastric acid production is com- Consequences of Gastrointestinal
monly thought to increase in critical illness, although Hypoperfusion
evidence suggests that many critically ill patients do not
hypersecrete gastric acid with increased gastric pH being The consequences of gastrointestinal hypoperfusion are
13
observed in some critically ill patients, even in the absence significant, and include disruption of the physical barrier
of pharmacological inhibition of gastric acid secretion. 14,15 to pathogens; disruption of chemical control of bacterial
The ability of the small intestine to absorb nutrients can overgrowth; decreased peristalsis; and reduced immuno-
be impaired during critical illness, although most criti- logical activities of gastrointestinal-associated lymphoid
16
cally ill patients appear to be able to tolerate enteral tissue. In health, all of these mechanisms work efficiently
nutrition, making the clinical significance of impaired to contain bacteria within the gastrointestinal tract.
absorption unclear. During critical illness, however, reduced oxygenation
contributes to decreased cellular function and failure of
Some alterations to normal gastrointestinal physiology in the protective mechanisms described in Table 19.2. Con-
critical illness relate to hypoperfusion and decreased oxy- sequently, bacterial proliferation and translocation from
genation in this area and have high metabolic demands. the gastrointestinal tract to the systemic circulation may
Historically, gastrointestinal dysfunction in critical illness occur. 22

508 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 19.2 Protective mechanisms of the gastrointestinal system and impact of critical illness 1,3-12

Mechanism Action
Motility Propels bacteria through the GI tract. In critical illness, motility may be altered because of enteric nerve
impairment and altered smooth muscle function, inflammation (mediated by cytokines and nitric oxide),
gut injury, hypoperfusion, medications (opioids, dopamine), electrolyte disturbances, hyperglycaemia,
sepsis and increased intracranial pressure. 3
Hydrochloric acid secretion Reduces gastric acidity and destroys bacteria. Parietal cells in the stomach produce hydrochloric acid and
keep the intragastric environment relatively acidic (pH approx 4.0). An acidic pH has bactericidal and
bacteriostatic properties, thus limiting overgrowth in the stomach.
4
Bicarbonate Bicarbonate ions bind with hydrogen ions to form water and carbon dioxide, preventing the hydrogen ions
(acid) from damaging the duodenal wall. 5
Bile salts Bile salts provide protection against bacteria by breaking down the liposaccharide portion of endotoxins, 6
thereby detoxifying gram-negative bacteria in the gastrointestinal tract. The deconjugation of bile salts
into secondary bile acids inhibits the proliferation of pathogens and may destroy their cell walls. 7
Mucin production Prevents the adhesion of bacteria to the wall of the GI tract. Mucous cells secrete large quantities of very
thick, alkaline mucus (approximately 1 mm thick in the stomach). Glycoproteins present in the mucus
prevent bacteria from adhering to and colonising the mucosal wall. 8
Epithelial cell shedding Limits bacterial adhesion. The mucosal lining of the entire gastrointestinal tract is composed of epithelial
cells that create a physical barrier to bacterial invasion. These cells are replaced approximately every 3–5
days limiting bacterial colonisation.
9
Zonea occludulns (tight junctions The junctions between epithelial cells provide a barrier to microorganisms. Intermediate junctions (zonula
surrounding each cell in the adherens) function primarily in cell–cell adhesion, while the tight junctions (zonula occludens) limit the
epithelial sheet) movement of bacteria and toxins across the gut wall. 10
Gut-associated lymphoid tissue Protection against bacterial invasion is provided by gut-associated lymphoid tissue, capable of cell-
11
mediated and humoral-mediated immune responses. 12
Kupffer cells Kupffer cells in the liver and spleen provide a back-up defence against pathogens that cross the barrier of
the gastrointestinal wall and enter the systemic circulation. 1




Changes in gastrointestinal perfusion also has the capac- decreased pepsin secretion. It is also possible that secre-
ity to affect hepatic perfusion, oxygenation and function. tion of digestive enzymes might also be influenced
In approximately 50% of critically ill patients, ischaemic by critical illness-induced pancreatitis, although clear
hepatitis or ‘shock liver’ occurs, which is evidenced by data demonstrating this level of dysfunction are
jaundice, elevation of liver function tests or overt hepatic unavailable. 16
23
dysfunction. Ischaemic hepatitis can vary from a mild
elevation of serum aminotransferase and bilirubin levels NUTRITION
in septic patients, to an acute elevation following haemo-
dynamic shock. Ischaemic hepatic injury influences Optimal nutritional support in the critically ill aims to
morbidity and mortality but remains underdiagnosed, prevent, detect and correct malnutrition, optimise the
probably because the clinical signs become apparent long patient’s metabolic state, reduce morbidity and improve
24
after hypoperfusion has occurred. Physiological changes recovery. The metabolic response of stress or injury is
contributing to ischaemic hepatitis include changes to hypermetabolism. There is an increased release of cyto-
the portal and arterial blood supply as well as hepatic kines (e.g. interleukin-1, interleukin-6, tumor necrosis
microcirculation. The degree to which the liver is damaged factor-α) and production of counter-regulatory hormones
is directly related to the severity and duration of hypo- (e.g. catecholamines, cortisol, glucagon and growth
perfusion, and both anoxic and reperfusion injury can hormone) that induce catabolism and oppose the ana-
25
damage hepatocytes and the vascular endothelium. 23 bolic effects of insulin. Hypercatabolism occurs with the
imbalance between anabolism (i.e. the chemical process
ALTERATIONS TO NORMAL METABOLISM by which complex molecules, such as peptides, proteins,
polysaccharides, lipids and nucleic acids, are synthesised
IN CRITICAL ILLNESS from simpler molecules) and catabolism (i.e. the conver-
There is little information describing the changes to the gent process, in which many different types of molecules
exocrine function in the gastrointestinal system during are broken down into relatively few types of end prod-
critical illness, and it is uncertain how critical illness ucts). To compensate for the altered metabolic regulation,
influences the metabolism of nutrients. While there is neuroendocrine stimulation increases the mobilisation
data to demonstrate that the secretion of hydrochloric and consumption of nutrients, such as glycogen and
acid by the parietal cells in the stomach is decreased, it is protein, from existing body stores. As the metabolic rate
not certain whether the exocrine failure also extends to a rises, nutritional requirements in critical illness are

Gastrointestinal, Liver and Nutritional Alterations 509

increased, characterised by a rise in resting energy expen-
diture and oxygen consumption, which in some critically TABLE 19.3 Nutritional indices
26
ill patients can be increased by over 50%. Depletion of
body energy stores result from alterations in protein, car- Assessment Limitations in critical illness
27
bohydrate and fat metabolism. In addition to the rise 40,43
in metabolic demands, patients who are critically ill often Subjective global Not validated in the critically ill
assessment
experience a concomitant fall in nutritional intake. The
metabolic and nutrition alterations vary with the stress Biochemical
markers:
level, severity of illness, type of injury, organ dysfunction ● albumin Decreased sensitivity because of 20-day
and nutrition status. 25 half-life; influenced by fluid balance/shifts 42
● transferrin Half-life of 8 days but lacks the sensitivity and
To maintain normal cellular function, body cells require specificity for determining nitrogen
adequate amounts of the six basic nutrients: carbohy- balance; influenced by fluid balance/shifts
43
drates, fats and proteins to provide energy, vitamins, min- ● prealbumin Most sensitive with a half-life of 2 days, but
44
erals and water to catalyse metabolic processes. Unlike changes may result from the metabolic
normal metabolism, which preferentially uses carbohy- response to illness rather than change in
drates and fats for energy, the hypermetabolic state asso- nutritional status; influenced by fluid
balance/shifts
ciated with critical illness consumes proportionally more
fats and proteins than carbohydrates to generate energy. Delayed Used to assess the patient’s immune status,
28
As a consequence of the gluconeogenesis and the synthe- hypersensitivity but alterations can be related to underlying
42
disease rather than nutritional status
sis of acute-phase proteins, there is a decrease in lean
body mass and negative nitrogen balance. Skeletal muscle Mechanical characteristics of skeletal muscle
function influenced by energy stores rather than
loss of muscle mass 42
CONSEQUENCES OF MALNUTRITION
When adequate and timely nutrition support is not pro-
vided, body energy and protein depletion can occur with importance of nutritional assessment and the impact of
negative consequences on patient outcome. Critically ill malnutrition in the critically ill informs management and
29
30
patients require adequate nutrition to limit muscle is likely to improve outcomes.
wasting, respiratory and gastrointestinal dysfunction and Determining Nutritional Requirements
alterations in immunity, all of which are associated with
30
malnutrition. Respiratory support is often necessary Determining caloric requirements is largely dependent
during critical illness, and changes in respiratory muscle on energy expenditure, influenced by patient activity,
function and ventilatory drive may contribute to an stage of illness, type of injury and previous nutritional
42
increase in the number of ventilator days. Furthermore, status. Indirect calorimetry is the ‘gold standard’ and
infection rates may be increased in malnourished criti- most precise way of determining the nutritional require-
45
cally ill patients. The decrease in lean body mass and ments in critical illness. Energy expenditure is measured
negative nitrogen balance is associated with delayed using the oxygen consumption obtained from carbon
wound healing and a higher risk of infection. 28 dioxide levels (PaCO 2 ), or using a metabolic monitor. It
is infrequently used in critical care settings, possibly
These complications contribute to increased length of because of the high equipment costs and unreliability in
31
stay, cost, morbidity and mortality. The degree of critical the critically ill. 46
illness and hypercatabolism varies between patients and
is often difficult to accurately determine. For this reason Calculating basal energy expenditure using the Harris-
it is necessary to assess, as accurately as possible, the Benedict equation is a common, but less precise, method
42,47,48
nutritional requirements of each individual patient. of determining nutritional requirements. The Harris-
Benedict equation, and others, takes into account the age,
NUTRITIONAL ASSESSMENT height, weight and gender of the patient, with adjust-
ments made for treatment, disease process and metabolic
The majority of studies report cumulative energy deficit state. Importantly, these equations fail to find any signifi-
or caloric debt is associated with worse clinical cant benefits in outcomes, most likely because they do
36
outcomes. 32-35 Krishnan and colleagues, however, not measure energy requirement. 49
describe better clinical outcomes for patients fed fewer
than the target nutrition goals when compared to those The Prognostic Inflammatory Nutrition Index (PINI) uses
who received near target goals. Nutritional assessment the elevations in acute phase proteins (alpha-1-acid gly-
includes patient history, physical examination and assess- coprotein and C-reactive protein [CRP]) that occur with
ment of nutritional indices (see Table 19.3), but is often simultaneous reductions in transport proteins (albumin
unreliable in the critically ill patient. 37,38 Clinical judge- and pre-albumin) in a simple formula to stratify critically
50
ment remains the most common way of assessing a ill patients by risk of complications or death.
patient’s nutritional status, and is shown to be as reliable NUTRITION SUPPORT
as biochemical tests. 39-41 Clinical judgement takes into
consideration recent weight loss, reduced dietary intake, For patients in ICU who are unable to take oral nutrition,
anorexia, vomiting, diarrhoea, muscle wasting and enteral nutrition (EN), parenteral nutrition (PN) or com-
42
signs of nutritional deficiency. Appreciation of the bined EN and PN is available. The best method of

510 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

providing nutrition to the critically ill who cannot have and institutions, 24,58,93-95 primarily as a consequence of
oral feeding is controversial. Infectious complications the shortage of reliable and valid research into the
51
have been associated with PN when used alone, but no effective delivery of enteral nutrition. In the absence of
differences in infectious complications were seen with strong research evidence, rituals are embraced and rarely
52
86
concurrent use of EN and PN. In a meta-analysis, PN challenged. Furthermore, the implementation and
was associated with reduced mortality when comparing sustainability of guidelines is influenced by multiple
PN with delayed EN despite the increased risk for infec- factors, e.g. clinicians, patients, context and contents of
51
tious complications associated with PN. Meta-analyses guidelines. 96
are limited by the quality of the studies included in the
analyses. 53,54 Recent guidelines advocate early enteral
nutrition 53,55-59 but better evidence is needed. 60 Management of Enteral Feeding
Routes of enteral feeding
ENTERAL NUTRITION The insertion of enteral feeding tubes into the correct
EN has benefits beyond the supply of nutrients to the place in the critically ill can be difficult because of reduced
61
body, including: cough reflex, altered sensorium and use of sedative
97
and narcotic medications. Wide-bore nasogastric tubes
62
● gut-derived mucosal immunity and decrease in
septic complications 63-65 (sump tubes) are most commonly used in the critically
● preservation of gastrointestinal mucosal integrity 66,67 ill in the early stages of enteral feeding. Because long-term
● improved gastrointestinal mucosal cell growth and use of wide-bore tubes can contribute to sinusitis, a fine-
replacement 68 bore feeding tube is often introduced if enteral feeding is
● increased gastric mucosal blood flow. 69 expected to continue beyond a few days. Should pro-
longed enteral feeding be anticipated (longer than 1
Absence of enteral nutrients (despite the provision of PN) month), gastrostomy, duodenostomy or jejunostomy
98
has been linked to atrophy of the intestinal villi, a reduc- tubes may also be used. Postpyloric feeding has not
tion in the number of epithelial cells produced, reduced been shown to be beneficial over gastric feeding, 99,100 but
gastrointestinal mucosal thickness, and ineffective func- is useful for later enteral feeding in patients if gastric
tioning of the intestinal brush border enzymes of the atony is present and the patient has persistent high gastric
gastrointestinal mucosa. 59,70-73 Stimulating and improving residual volumes. 101
gastrointestinal immune function is an important goal of
59
early EN. Early enteral feeding (within 48 hours) is For some critically ill patients, gastric secretions may
102
recommended. 55,56 increase when small bowel feeding is initiated. A
double-lumen tube is available, one lumen for gastric
Hypocaloric Intake in the Critically Ill aspiration and decompression and the second for simul-
taneous jejunal feeding, but these tubes are not widely
A significant number of hospitalised patients receiving used in the clinical setting. 103
EN do not have their nutritional needs met. 70,71 Hypoca-
loric feeding in the first few days of critical illness may be
beneficial, 36,74-77 but results are conflicting. 34,78-80 The Assessment of enteral feeding tube placement
belief that early enteral feeding prevents gut dysfunction Correct placement of enteral feeding tubes in the criti-
81
independently of calorie intake perpetuates the accep- cally ill can be difficult. 104,105 Misplacement of the feeding
tance of administration of EN below the nutrition tube into the tracheobronchial tree are important
target. 33,70,82,83 In most cases, hypocaloric feeding is unnec- complications of tube insertion. Additional complica-
106
essary and avoidable. 84,85 Severe underfeeding over a short tions such as infusion of tube feedings, pneumothorax,
time particularly during the initial week of ICU stay is pneumonitis, hydropneumothorax, bronchopleural
associated with the formation of an energy debt that leads fistula, empyema and pulmonary hemorrhage have been
to increased infections, complications and longer ICU reported. 107-112 While confirmation of tube placement is
34
stays. Factors that contribute to unintentional hypoca- routinely done with radiography, this approach does not
loric feeding include staffing shortages, unavailability of prevent incorrect placement occurring during insertion;
feeds/equipment, low priorities for feeding, fasting for less reliable methods of confirming tube placement
clinical investigations, blockages in feeding tubes and include the use of auscultation and aspiration, and other
86
variations in feed prescriptions. Delivery issues, such as novel methods such as capnography. 105,113
elective interruption for investigative procedures or oper-
ations, contributed to hypocaloric feeding with only 76% Assessment of feeding tube placement by auscultation of
87
of prescribed feeds delivered to critically ill patients. air insufflated into the stomach remains a common clini-
Similar results were observed in mechanically-ventilated cal practice. Auscultation should not be used as the sole
88
patients, where more than 36% of patients received less method to determine placement of the gastric tube
than 90% of their caloric requirements. because it is unreliable. Other important points are:
● Aspirate from critically ill patients who receive con-
Enteral Feeding Protocols tinuous feedings may have the appearance of
Enteral feeding protocols improve the delivery of enteral unchanged formula, regardless of the site of the
feeds 87,89,90 and have been shown to improve clinical feeding tube, therefore this method should not be
outcomes. 83,91,92 But protocols vary widely between units used. 114

Gastrointestinal, Liver and Nutritional Alterations 511

● Analysis of the pH of gastric secretions is not reliable.
A pH of 0–5 may be used to indicate gastric placement TABLE 19.4 Methods of feed delivery
of enteral feeding tubes, although this technique may
be problematic for patients receiving histamine-2- Method Description
receptor antagonists or proton pump inhibitors. If the
aspirated fluid has a low pH, it may be assumed that Bolus ● Delivery of a large volume of tube feed into the
stomach over a short period of time (>100 mL)
the fluid originated in the stomach but the pH of fluid ● Associated with complications, such as
115
from an infected pleural space can also be acidic, aspiration and vomiting 127,128
therefore pH testing as a sole method to determine
tube placement is not recommended. 116 Intermittent ● A several-hour infusion a few times a day (e.g.
150 mL/h for 3 hours, three times per day), or
● End-tidal CO 2 (ETCO 2 ) detectors: capnometry and delivered over a longer period (12–16 hours)
capnography. Capnometry and capnography use with an 8–12-hour rest period 127
ETCO 2 CO 2 detectors to evaluate enteral tube place- ● Allows gastric acidity and therefore limits
ment but they are not used in routine clinical bacterial overgrowth
practice. 107,117-122 Differentiating between oesophageal, ● Requires a higher hourly rate to meet caloric
stomach or intestinal placement is not possible. 116 requirements
● Pepsin/trypsin. Measuring the concentrations of Continuous ● The delivery of small amounts of formula per
pepsin and trypsin in feeding tube aspirates can be hour over a 24-hour period 129
used as a method of predicting tube placement ● May make caloric requirements more
however methods to measure pepsin and trypsin at achievable
the bedside are currently unavailable. 123 ● Continuous dilution of gastric acid may
contribute to bacterial overgrowth
Ongoing assessment of feeding tube placement is essen-
tial, as feeding tubes may migrate after initial placement. their daily caloric requirements should be employed.
Marking the feeding tube at the point where it exits the When a patient has experienced a prolonged period of
nose and measurement of tube length protruding from starvation or total parenteral nutrition, the approach
the anterior nares will facilitate detection of migration of to enteral feeding is somewhat more reserved, as the risk
the enteral tube. Radio-opaque tubes have markers to of refeeding syndrome is increased. 130-132 Although not
enable accurate measurement and documentation of common, this syndrome is associated with severe derange-
tube position. It should be used with the methods previ- ment in fluid and electrolyte levels (particularly hypo-
ously described for ongoing assessment. phosphataemia, hypomagnesaemia and hypokalaemia),
and may result in significant morbidity and mortality.
In the absence of X-ray, several approaches should be
used in combination to verify tube position. Metheny Managing complications of enteral feeding
114
and colleagues found measuring: (a) length of tubing Once enteral feeding is established, it is important to
extending from the insertion site, (b) volume of aspirate assess for such complications as:
from the feeding tube, (c) appearance of the aspirate, and
(d) pH of the aspirate were able to correctly differentiate ● feeding intolerance
between gastric and bowel tube placement during con- ● gastric distension
tinuous feedings in 81% of the predictions. Ongoing ● vomiting
assessment of feeding tube placement is also essential, as ● diarrhoea
feeding tubes may migrate after initial placement. ● pulmonary aspiration
● hyperglycaemia
Feeding regimens ● hypercarbia
● electrolyte imbalances
Once the enteral feeding tube is successfully placed, ● feed contamination.
administration of the feeding solution can begin using a
variety of methods, including bolus, intermittent and This intolerance to enteral feeding can result in gastric
continuous enteral feeding (see Table 19.4). Bolus enteral distension, diarrhoea and increased GRV. 87,133,134
feeding is rarely used in the critically ill, but it is less clear
whether intermittent or continuous feeding is more
beneficial. 124-126 Because of inconclusive evidence regard- Practice tip
ing feeding regimens, decisions are best based on indi-
vidual patient assessment and the clinician’s clinical When evaluating gastric residual volume in relation to the rate
judgement. of enteral feeding, remember to take into account the produc-
tion of gastric secretion, which can be as much as 2500 mL/day.
Commencing enteral feeding
The starting rate for enteral feeding is controversial, with Critically ill patients exhibit elevated gastric residual
86
suggestions in the range of 10–100 mL/h, and the com- volume for a variety of reasons including feeding
monest starting rate being 30 mL/h, despite there being intolerance 135-139 and reduced gastric motility. 135,136,140
no empirical data on which to base this recommenda- Monitoring tolerance to enteral feeding through the mea-
tion. Increasing the rate of enteral feeding is equally vari- surement of gastric residual volume has always been
able, but strategies to progress patients towards meeting viewed as an important aspect of nursing management,

512 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

although consensus on what constitutes a high gastric is difficult, even for experienced clinicians. High gastric
residual and any recommendations for interventions residual volumes have been linked to the potential for
remain controversial. Ceasing feeds in response to gastric pulmonary aspiration, although this has not been shown
141
141
residual volume is questionable, particularly as a bal- in research. Oropharyngeal secretions can contribute to
anced enteral diet in itself has a prokinetic effect. 142 nosocomial pneumonia and subglottic aspiration has
improved outcomes. 169 Nursing strategies to improve
gastric emptying includes elevation of the head of the bed
Practice tip 30–45 degrees (unless otherwise contraindicated),
170
In determining feeding intolerance, a single high gastric resid- reducing the likelihood of gastro-oesophageal reflux,
ual volume in the absence of physical examination or radio- which is present in up to 30% of patients in the supine
graphic findings should not result in the cessation of enteral position.
feeding. Persisting with enteral feeding has demonstrated ben- Prokinetic agents can improve gastric emptying and
efits. It is thought that a balanced enteral diet, in itself, has a feeding tolerance, and avoid gastro-oesophageal reflux
prokinetic effect. 143 and pulmonary aspiration. Cisapride, erythromycin and
metoclopramide have all been used clinically to improve
Development of diarrhoea is another complication for gastrointestinal motility. A systematic review noted that,
enterally fed patients, and is a common reason why as a class of drugs, promotility agents have a beneficial
enteral feeding is often reduced or ceased. Diarrhoea may effect on gastrointestinal motility in the critically ill
171
contribute to fluid and electrolyte disorders, patient (and patient. These prokinetic agents do, however, have
nursing) distress, and a higher cost of patient care. 144 undesirable effects. Use of erythromycin is associated
Unfortunately, defining diarrhoea is problematic, as it is with the development of bacterial resistance, and meto-
a subjective assessment that relies on nursing interpreta- clopramide is associated with numerous systemic side
tion rather than on quantifiable assessment of stool effects. Erythromycin is more effective than metoclo-
weight. 145 There are various aetiologies for diarrhoea in pramide in treating gastric intolerance among patients
the enterally fed, critically ill patient, including: receiving enteral nutrition. 172 However, combination
therapy with erythromycin and metoclopramide is more
● antibiotic use 146 effective than erythromycin alone in improving the deliv-
● hypoalbuminaemia 144 ery of enteral nutrition. 173
● use of histamine-2 receptor antagonists 147
● contamination of enteral feeding solution. 148 Assessment of pulmonary aspiration
Probiotic administration may limit the development Despite preventive strategies, pulmonary aspiration may
of diarrhoea, 149 although its efficacy is yet to be still occur in some patients, and accurate assessment is
established. 150,151 essential. Common methods that can be performed easily
at the bedside to determine whether a patient has expe-
Enteral feeding solutions present an excellent medium rienced aspiration of gastric contents and/or enteral
for the growth of microorganisms, 152 and bacterial con- feeding formula follow:
tamination of enteral feeds is common. 153-155 Strategies to
limit bacterial contamination of enteral feeding solutions ● The dye method involves the addition of blue food
include: colouring to the enteral feeding formula, theoretically
making it possible to visualise gastric contents if
● meticulous preparation of feeding solutions and they have been inhaled into the tracheobronchial
equipment 156 tree. However, the use of blue dye is poorly stan-
● commercially prepared formula used in preference to dardised and has a low sensitivity in detecting micro-
decanted feeds 157-159 aspiration. 174 The use of methylene blue is not
● use of closed feeding systems 93,160,161 recommended because of associated side effects and
● limiting the time feeding solution is kept at high costs. 175 There have been case reports of blue
room temperature once opened and hang dye absorption describing discolouration of the skin,
times 93,148,157,162-168 urine, serum and organs, 176 and refractory hypoten-
● meticulous attention to hand washing and limiting sion and severe acidosis, suggesting poisoning by a
manipulation of the enteral nutrition bags and deliv- mitochondrial toxin. 177,178 These safety concerns,
ery system at the bedside 153,155 coupled with minimal benefits, have resulted in the
Despite hesitancy by nurses to persist with enteral feeding recommendation that the practice of using blue
in the presence of diarrhoea, there is no evidence to food colouring in enteral feeding solutions be
179
support the withholding of enteral feeding in critically ill abandoned.
patients unless there are significant disturbances in fluid ● Measurement of glucose in tracheobronchial secre-
and/or electrolyte balance. tions is another method to detect pulmonary aspira-
tion. 180 As these secretions normally contain <5 mg/
dL glucose, higher amounts of glucose may indicate
Prevention of pulmonary aspiration the aspiration of glucose-rich enteral feeding
68
An important complication of enteral feeding is the formula. However, differences in enteral feeding
development of pulmonary aspiration and nosocomial solutions affect the sensitivity of this method, with
pneumonia. Determining whether aspiration has occurred low glucose solutions being more difficult to detect.

Gastrointestinal, Liver and Nutritional Alterations 513

Also, patients not receiving enteral feeding can have
181
detectable glucose in aspirates. This is further con- TABLE 19.5 Components of TPN solutions
founded by the presence of blood, which is closely
associated with glucose values >20 mg/dL; conse- Component Implication
quently, any blood in the respiratory tract could con-
181
tribute to a false-positive result. These findings led Carbohydrate ● This should supply approximately 70% of the
patient’s non-protein to prevent protein
to the consensus that glucose monitoring in respira- catabolism needs. 190
tory secretions should also be abandoned. 179 ● Insulin production will usually be increased to
● Measurement of pepsin in tracheobronchial secre- maintain normoglycaemia, although some
tions has been used in an animal study suggested that patients, such as those with diabetes, may
the detection of pepsin, a component of gastric secre- require an insulin infusion to maintain
normoglycaemia.
tions, may be useful in determining pulmonary aspi- ● Glucose solutions over 25% are hyperosmolar
ration. 182 however, further investigation in acutely ill and may cause thrombophlebitis.
patients receiving enteral feeding is necessary. ● Glucose solutions mixed with lipids can
protect the vein from thrombophlebitis,
PARENTERAL NUTRITION provided osmolality is <800 mOsmol/kg. 189
The appropriate use of PN in the context of critical illness Lipids ● More energy-dense than carbohydrate
continues to be debated. 183-185 EN is the preferred method (9 kcal/g), and should provide 30–40% of the
non-protein energy.
of nutritional support because it is less expensive and is ● Available as a 10% (1 kcal/mL) or 20%
associated with fewer infectious and metabolic complica- (2 kcal/mL) solution.
tions than PN. However, it is not uncommon for critically ● Necessary to maintain cell wall integrity,
ill patients to have difficulty in meeting daily caloric prostaglandin synthesis and the absorption of
intake 34,71 and this may necessitate supplementation of lipid-soluble vitamins. 191
enteral nutrition with PN or the sole provision of nutri- ● Isotonic, so can be given via a peripheral line if
tional support through parenteral means (as TPN). For necessary.
patients who are unable to be fed by the enteral route Nitrogen ● A balance of crystalline amino acids supplying
and who were healthy prior to ICU admission, with no 0.2 g nitrogen per kg body weight is required
evidence of protein-calorie malnutrition, then it is recom- to achieve a nitrogen balance in most patients,
mended that PN be initiated after 3–7 days 186 of hospi- although some patients may utilise more
nitrogen.
talisation. 187 The lack of agreement on the efficacy of PN ● Some critically ill patients may utilise more
means that the use of this therapy varies both within and nitrogen and thus have higher requirements.
between countries. 58,186,187
Electrolytes ● Content varies in amino acid solutions, so
PN solutions contain carbohydrates, lipids, proteins, elec- content in relation to patient requirements
trolytes, vitamins and trace elements. PN, whether sup- needs to be considered.
plementary or complete, provides daily allowances of ● Monitoring of electrolyte status is essential,
nutrients and minerals. The components of PN are listed particularly serum phosphate levels if the
amino acid solution used is phosphate-free.
in Table 19.5. The addition of vitamins and trace ele- ● The balance between chloride and acetate is
ments to PN solutions is necessary, particularly as water- monitored, as administration of additional
soluble vitamins and trace elements are rapidly depleted sodium or potassium may result in acid–base
(see Table 19.6). Glucose is the primary energy source in imbalances.
PN solutions. Concentrations of 10–70% glucose may be
used in PN solutions although the final concentration of
the solution should be no more than 35%. The high TABLE 19.6 Trace elements in TPN 192
concentration of PN solutions can cause thrombosis so
PN is normally infused via a central venous catheter Trace element Action
(CVC). Peripheral administration can be considered
when the final solution concentration is 10–12%, 188 but Zinc Wound healing
is not usually used in the context of critical illness because Iron Haemoglobin synthesis
high volumes of PN would be required to meet caloric Copper Erythrocyte maturation and lipid metabolism
requirements. 189
Manganese Calcium and phosphorus metabolism
Catheter insertion, ongoing care and replacement are
similar to that with any other CVC. A dedicated CVC, or Cobalt Essential constituent of vitamin B12
lumen of a multilumen CVC, should be used for PN. 191,193 Iodine Thyroxine synthesis
Manipulation of the CVC and tubing should be avoided Chromium Glucose utilisation
to minimise infection of the catheter.
Routine monitoring of the patient’s fluid balance, glucose, STRESS-RELATED MUCOSAL DISEASE
biochemical profile, full blood count, triglycerides, trace
elements and vitamins is necessary. The patient is also The reported incidence of stress-related mucosal damage
assessed for signs of complications associated with the is variable 194 and complicated by definitions of end
administration of PN (see Table 19.7). points, difficulty in measuring the end points, and the

514 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 19.7 Short-term metabolic complications associated with total parenteral nutrition

Complication Cause Detection and treatment
Hyperosmolar coma Occurs acutely if a rapid infusion of hypertonic fluid is Daily blood samples, accurate measurements of fluid
administered. Infusion can cause severe osmotic diuresis, balance, routine blood samples. Reduce infusion
resulting in electrolyte abnormalities, dehydration and rate, correct electrolyte imbalances.
malfunction of the central nervous system.
Electrolyte Disturbances in serum electrolytes, particularly sodium Daily blood samples taken early in treatment to
imbalance potassium, urea and creatinine, may occur early in the detect abnormalities. Replacement fluid as
treatment of TPN. Electrolyte imbalances can be caused by required, extra intravenous fluids may be required
the patient’s underlying medical condition; requirements during the stabilisation period.
vary with individual patients’ needs. Can be caused by
inadequate or excessive administration of intravenous fluids.
Hyperglycaemia Critically ill patients may be resistant to insulin because of the Monitor the patient’s blood sugar 4-hourly after
secretion of ACTH and adrenaline. This promotes the commencement of treatment or as required.
secretion of glycogen, which inhibits the insulin response to Monitor daily urinalysis for glucose and ketones.
hyperglycaemia. An insulin infusion may be required to keep blood
sugar levels within prescribed limits.
Rebound May occur on discontinuation of TPN because hyperinsulinism Glucose infusion rate should be gradually reduced
hypoglycaemia may occur after prolonged intravenous nutrition. A rise in over the final hour of infusion before
serum insulin occurs with infusion, and thus sudden discontinuing. Some patients may receive a 10%
cessation of infusion can result in hypoglycaemia. glucose solution after cessation of TPN.
Hypophosphataemia Glucose infusion results in the continuous release of insulin, Monitor phosphate levels daily. Hypophosphataemia
stimulating anabolism and resulting in rapid influx of will usually appear after 24–48 hours of feeding.
phosphorus into muscle cells. The greatest risk is to Reduce the carbohydrate load and give phosphate
malnourished patients with overzealous administration of supplementation.
feeding. Patients who are hyperglycaemic, who require
insulin therapy during TPN or who have a history of
alcoholism or chronic weight loss may require extra
phosphate in the early stages of treatment.
Lipid clearance Lipids are broken down in the bloodstream with the aid of Blood samples should be taken after the first
lipoprotein lipase found in the epithelium of capillaries in infusion commences (within 6 hours) to observe
many tissues. A syndrome known as fat overload syndrome for lipid in the blood.
can occur when infusion of lipid is administered that is
beyond the patient’s clearing capacity, resulting in lipid
deposits in the capillaries.
Side effects of lipid Some patients suffer symptoms either during or after an Treat mild symptoms. If tolerated, the TPN solution of
infusion infusion of lipid mix parenteral nutrition. The exact cause is non-protein calories can be given in the form of
unknown. The patient may complain of headache, nausea or glucose. However, it is essential that the regimen
vomiting, and generally feels unwell. includes some fat to prevent the development of
fatty acid deficiency.
Anaphylactic shock This is a rare complication but may occur as a reaction to the It may be necessary to administer adrenaline and/or
administration of a lipid. steroids, and to provide supportive therapy as
required.
Glucose intolerance TPN using glucose as the main source of calories is associated Observe patients for signs of respiratory distress.
with a rise in oxygen consumption and CO 2 production. The Provide non-protein calories in the form of glucose
workload imposed by the high CO 2 production may lipid mix. Slow initial rate of infusion.
precipitate respiratory distress in susceptible patients,
particularly those requiring mechanical ventilation.
Liver function Abnormalities with liver function can be associated with TPN. Monitor liver function tests twice weekly. There are
May be attributable to hepatic stenosis with moderate several factors that may contribute to
hepatomegaly; patient may also develop jaundice. Liver development of abnormal liver function tests.
function tests often return to normal after cessation of These most often occur after a period of time and
therapy; however, TPN can lead to severe hepatic appear to be more of a problem when there is an
dysfunction in neonates. excess calorie intake or in glucose-based regimens.
ACTH = adrenocorticotrophic hormone.


heterogeneity of the patient populations. 195 With occult nasogastric lavage positive for bright red blood is used as
bleeding (drop in haemoglobin level or positive stool an endpoint to describe clinically overt bleeding. 198,199
occult blood test) as an endpoint, it is estimated that The incidence of clinically significant bleeding, that is
15–50% of critically ill patients would be reported to bleeding associated with hypotension, tachycardia, and a
have stress-related mucosal damage. 196,197 Reported inci- drop in haemoglobin level necessitating transfusion, is
dence is reduced to 25% or less when haematemesis or estimated to be 3–4%. 194

Gastrointestinal, Liver and Nutritional Alterations 515



TABLE 19.8 Factors contributing to stress-related mucosal disease 204

Factors Mechanism Action
Protective Mucosal prostaglandins Protect the mucosa by stimulating blood flow, mucus and bicarbonate production 205
mechanisms Stimulate epithelial cell growth and repair
Mucosal bicarbonate barrier Forms a physical barrier to acid and pepsin, preventing injury to the epithelium 206
Epithelial restitution and Epithelial cells rapidly regenerate but the process is highly metabolic and may be impaired
regeneration by physiological stress 206
Mucosal blood flow Mucosal blood flow helps remove acid from the mucosa, supplies bicarbonate and oxygen
to the mucosal epithelial cells 207
Cell membrane and tight Tight junctions between mucosal epithelial cells prevents the back diffusion of hydrogen
junctions ions 208
Factors Acid Acid is a key issue in the pathogenesis of stress-related mucosal injury however not all
promoting critically ill patients hypersecrete acid. 14,208 However small amounts of acid may still cause
injury injury and the prevention of acid secretion has led to a reduction in injury 209
Pepsin May cause direct injury to the mucosa 210
Facilitates the lysis of clots 211
Mucosal hypoperfusion Reduced mucosal blood flow results in reduced oxygen and nutrient delivery, making
epithelial cells susceptible to injury. 208
Contributes to mucosal acid-base imbalances
Results in the formation of free radicals
Reperfusion injury Nitric oxide, which causes vasodilation and hyperaemia, is released during hypoperfusion
and results in an increase in cell-damaging cytokines
Intramucosal acid–base The mucus layer protects the epithelium and traps bicarbonate ions that neutralise acid thus
balance a decrease in bicarbonate secretion results in intramucosal acidosis and local injury 206
Systemic acidosis Results in increased intramucosal acidity 207
Free oxygen radicals Generated as a result of tissue hypoxia, free oxygen radicals cause oxidative injury to the
mucosa 212
Bile salts Bile salts reflux from the duodenum into the stomach and may have a role in stress-related
damage although the exact mechanism is uncertain 213
Heliobacter pylori Conflicting results about the role of H. pylori as a cause of stress-induced mucosal disease in
the critically ill 214



Factors influencing the development of stress-related higher than for those who do not develop this complica-
200
200
mucosal disease include splanchnic hypoperfusion tion. Consequently, there is a strong imperative to
which may influence mucosal ischaemia and reperfusion implement stress-ulcer prophylaxis, particularly in those
201
injury, maintenance of the gastric mucosa by sufficient patients who are considered at risk.
202
microcirculation and the mucus-bicarbonate gel layer,
decreased prostaglandin levels which impairs mucus PREVENTING STRESS-RELATED
replenishment and increased nitric oxide synthase which MUCOSAL DISEASE
203
contributes to reperfusion injury and cell death. The Prophylaxis for stress-related mucosal disease is often
protective mechanisms and factors which promote injury part of the care of the critically ill although evidence
are detailed in Table 19.8. demonstrating an added benefit when this therapy is
applied to those patients who are not identified as at risk
RISK FACTORS FOR STRESS-RELATED for developing stress-related mucosal disease, is limited.
201
MUCOSAL DISEASE Nevertheless, it is common for the majority of critically
A number of risk factors are associated with the develop- ill patients to receive some form of stress-ulcer prophy-
ment of stress-related mucosal disease, including respira- laxis during their episode of critical illness. There are a
tory failure requiring at least 48 hours of mechanical variety of pharmacological strategies that can be used to
215
ventilation and coagulopathy, acute hepatic failure, prevent stress ulcers from developing. These include ant-
hypotension, chronic renal failure, prolonged nasogastric acids, sucralfate, histamine-2-receptor antagonists and
201
tube placement, alcohol abuse, sepsis and an increased proton pump inhibitors (PPIs).
serum concentration of anti-Helicobacter pylori (H. pylori) Antacids
immunoglobulin A. 216
Antacids directly neutralise gastric acid and have been
Mortality rates for critically ill patients who develop shown to be effective in reducing significant stress-related
stress-related mucosal disease approximate 50–77% and bleeding. One of the disadvantages of this therapy is
217

516 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

the time-intensive nature of administering antacids every gastric epithelium, stimulates mucus and bicarbonate
1–2 hours. Furthermore, antacids can contribute to secretion, stimulates epithelial renewal, improves mucosal
further complications (e.g. aluminium toxicity, hypo- blood flow and enhances prostaglandin release. 196 Given
phosphataemia, diarrhoea or hypermagnesaemia). These orally or via a nasogastric tube, sucralfate is well tolerated
factors have led to their infrequent use within the critical but appears to be less effective than H 2 RAs in decreasing
care setting. 200,218,219 clinically significant bleeding. 228 Earlier reports compar-
ing sucralfate with ranitidine showed a decrease in the
Histamine-2-Receptor Antagonists development of pneumonia in those patients receiving
sucralfate; however, these findings were not supported in
Histamine-2-receptor antagonists (H 2 RAs) are commonly 228
used in the critically ill to inhibit the production of gastric a subsequent Level I randomised controlled trial.
acid, which is achieved by the drug binding to the
histamine-2 receptor on the basement membrane of the Enteral Nutrition
parietal cell. 196 However, gastric acid secretion may also It is thought that the presence of enteral feeding solution
occur through stimulation of the acetylcholine or gastrin results in an increase in intragastric pH, thereby minimis-
220
receptors present in parietal cells; therefore complete ing acid injury. Several studies have demonstrated a lower
blocking of gastric acid production does not occur when incidence of stress-related bleeding in mechanically-
230
H 2 RAs are used. A further limitation of H 2 RA is the devel- ventilated 229 and burn patients, while others were
opment of tolerance that may occur within 72 hours unable to show a significant effect on increasing gastric
221
231
of administration. Nevertheless, this pharmacological pH. A lack of well-designed prospective studies examin-
strategy to prevent stress-related mucosal disease remains ing the role of enteral nutrition in stress-ulcer prophylax-
commonplace in critical care. 222 sis prevents the use of this therapy as a sole therapeutic
The decrease in gastric acidity as a result of H 2 RA use may agent for this purpose. 201
be beneficial from the perspective of preventing stress-
related mucosal disease, but changes in gastric pH could LIVER DYSFUNCTION
lead to bacterial overgrowth in the stomach, microaspira-
tion, and consequently an increase in the incidence of The liver performs the vital functions of controlling meta-
nosocomial pneumonia, 223 although there is some bolic pathways, participating in digestion, immunologi-
research that does not support this notion. 209 cal protection, detoxifying chemicals and clearing toxins
and drugs. Therefore, liver dysfunction can have broad-
Proton Pump Inhibitors ranging consequences, for example alterations in meta-
bolic processes (such as glucose homeostasis), failure to
Proton pump inhibitors (PPIs) have a greater ability to produce clotting factors (with resultant severe haemor-
maintain an increased intragastric pH than H 2 RAs. 224 rhage) and ‘other organ’ effects such as brain, lung and
These drugs work by irreversibly binding to the proton kidney dysfunction and injury. Accordingly, liver dysfunc-
pump, effectively blocking all three receptors responsible tion can impact substantially on the nursing care needs
for gastric acid secretion by the parietal cell. 196,201 PPIs of the critically ill patient.
are also able to limit vagally-mediated gastric acid
secretion. 200
RELATED ANATOMY AND PHYSIOLOGY
Clinical evaluation of the efficacy of PPIs is somewhat The liver is the largest internal organ, weighing approxi-
limited; few studies have specifically studied the prophy- mately 1200–1600 g in the adult. It receives approxi-
lactic use of PPIs for stress-related mucosal diseases 12,225-227 mately 25% of total cardiac output through a dual
and many are limited by small sample sizes. Although vascular supply consisting of the hepatic artery and portal
PPIs are similar to H 2 RA in the ability to raise the gastric vein. 232 About 75% of the hepatic blood flow arises from
pH above 4, a level considered adequate to prevent stress the portal vein with the remaining 25% from the hepatic
ulceration, PPIs are more likely to maintain the pH at artery. Anatomically, the liver consists of 4 lobes: the
greater than 6, which may be necessary to maintain major left and right lobes, and the minor caudate and
clotting in those patients at risk of rebleeding from peptic quadrate lobes. The right lobe is considerably larger than
ulcer. 201
the left lobe. Functionally, the liver is divided into eight
PPIs that may be administered intravenously include segments each with their own inflow and outflow blood
omeprazole, esomeprazole and pantoprazole. Omepra- supply and biliary drainage. Hepatic lobules, or liver
zole has the highest potential for drug interation and acini, are small units consisting of a single or double layer
interferes with the metabolism of some drugs commonly of hepatocytes arranged in plates interspersed with capil-
used in intensive care, including cyclosporine, diazepam, laries (sinusoids) that receive inflowing blood from the
phenytoin and warfarin. Pantoprazole has the lowest portal vein and hepatic artery. To safeguard the body from
203
potential for drug interactions. 200 the entrance of toxins absorbed from the intestines, the
sinusoids are lined by macrophages known as Kupffer
Sucralfate cells. The hepatic vein then drains effluent blood from
1
Sucralfate provides protection against stress-related the liver into the general circulation.
mucosal disease through a number of mechanisms. The liver has a drainage system for bile (used in the
Sucralfate provides a protective barrier on the surface breakdown and absorption of lipids from the intestine),

Gastrointestinal, Liver and Nutritional Alterations 517

which is secreted by the hepatocytes. Bile drains from the areas of surviving cells to restore the lost tissue whilst
hepatocytes into bile ducts and then into the common maintaining homeostasis during hepatic regenera-
hepatic duct, before passing into the gall bladder via the tion. 234,239,240 However, with chronic injury, fibrosis or
common bile duct. scarring occurs, resulting in the loss of the functional
architecture and cell mass and ultimately in cirrhosis.
The arrangement of the circulation to the liver with its
rich vascular architecture enables it to perform the vital Cirrhosis results in destruction of the normal liver vascu-
functions of carbohydrate, fat and protein metabolism; lature, increased resistance to blood flow, and back pres-
production of bile to aid in digestion; the production, sure into the portal circulation. Dilation of the venous
conjugation and elimination of bilirubin; immunologi- system leading into the liver results in the formation of
241
cal and inflammatory responses; glycogen storage; and varices.
detoxification of toxins and drugs. 1 Liver cell injury may occur to such a degree that a critical
amount of hepatic necrosis results in the failure of the
As the kidneys are responsible for clearance of water- liver to maintain metabolic, synthetic and clearance func-
soluble toxins from the body, the liver clears protein tions leading to death. Liver cell injury may also occur
(largely albumin)-bound toxins and excretes them into more slowly, giving rise to chronic liver injury. 236
the gastrointestinal tract for elimination, or reabsorption
in water-soluble form for subsequent renal excretion. EPIDEMIOLOGY OF VIRAL HEPATITIS

MECHANISMS OF LIVER CELL INJURY In developed countries such as Australia and New
Zealand, viral infection, primarily from hepatitis B and
Liver cell injury and death can occur either as a direct hepatitis C viruses, is the major cause of liver cell injury
result of injury to the cell, resulting in cell necrosis, or as leading to liver failure. 242,243 Although viral hepatitis can
a result of ‘cellular stress’ and the triggering of apoptotic result in acute liver failure, it more often results in chronic
pathways, leading to ‘programmed cell death’. 233 Major disease that may lead to cirrhosis and hepatocellular
factors for the triggering of the apoptotic pathway are carcinoma. 243 While the prevalence of hepatitis B in Aus-
hypoxia with resulting ischaemia and reperfusion; reac- tralia and New Zealand is generally low, infection rates
tive oxygen metabolites resulting from alcohol or drug among social subgroups, such as the socially disadvan-
ingestion; accumulation of bile acids resulting from cho- taged, migrants from Asian countries, injecting drug
lestasis; and inflammatory cytokines such as tumour users, homosexual males, and those with a history of
necrosis factor alpha (TNF-α). 233 The apoptotic pathway incarceration, are high. 244,245 Hepatitis C is blood-borne,
results in the deconstruction of the cellular structure from with intravenous drug use the cause of about 80% of
the inside out, while necrosis results in cell rupture and hepatitis C infections. Blood screening has greatly reduced
release of cellular contents. Although these processes may the incidence of hepatitis C infections. 246 In Australia in
overlap, it is thought that the apoptotic pathway is a way 2009, approximately 217,000 people were living with
of preventing the inflammatory response that is triggered chronic hepatitis C infection, with 46,000 in the moder-
with cell necrosis. The activation of the inflammatory ate to severe liver disease category. 247 However, about
response results in secondary liver cell injury and contrib- 25% of people with exposure to hepatitis C virus have
utes to the multiple organ dysfunction seen in liver cleared the virus and are not chronically infected. It is
failure. 233,234 estimated that the number of people with hepatitis C will
The degree and time course of liver cell damage from viral increase in Australia and New Zealand due to lack of
247-249
hepatitis depends on the immune response. Immune rec- access to antiviral therapy. Vertical transmission
ognition and destruction of infected cells may result in (transmission from the mother to the child during the
either clearance of the virus or ongoing inflammation, perinatal period) at birth is a major cause of such infec-
243
cell death and fibrosis if the virus is not cleared. This tions in children.
process may progress over 20–40 years to cirrhosis and
hepatocellular carcinoma. 235 Chronic excessive alcohol Practice tip
intake may also result in a slower chronic course of liver
injury that eventually results in cirrhosis, liver failure or Use appropriate infection control practices and personal pro-
hepatocellular carcinoma. 236 tective equipment for patients at high risk of hepatitis B virus
(HBV) and hepatitis C (HCV) infections.
Liver cells may also be injured by the toxic effects of drugs
or their metabolites, as in paracetamol overdose, or by
drugs at therapeutic doses (e.g. non-steroidal anti- LIVER DYSFUNCTION/FAILURE
inflammatory drugs, phenytoin, antimalarial agents). Liver dysfunction can be acute or chronic. Chronic liver
Other poisoning from the ingestion of mushrooms (e.g. disease is usually associated with cirrhosis and can
Amanita phalloides), and from recreational drug use (e.g. develop from viral (hepatitis B and C), drug (alcohol),
ecstasy and amphetamines), may result in liver cell death metabolic (Wilson’s disease), or autoimmune (primary
and liver failure. 237 Diseases of the biliary system such as biliary cirrhosis) conditions. Acute liver failure (ALF) is
primary biliary cirrhosis and primary sclerosing cholan- an uncommon condition associated with rapid liver dys-
gitis also result in liver dysfunction and failure. 238
function leading to jaundice, hepatic encephalopathy and
250
The liver has a remarkable regenerative capacity. After coagulopathy. The term ‘fulminant hepatic failure’ is
injury and necrosis, liver cells rapidly regenerate around often used synonymously; however, it has been proposed

518 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

that ‘hyperacute’, ‘acute’ and ‘sub-acute’ liver failure
251
should be used instead. In this classification, hyper- TABLE 19.9 West Haven grading of hepatic
acute refers to patients who develop encephalopathy encephalopathy 258,261
within 7 days of the onset of jaundice, acute liver failure
should be used in patients between 8–28 days from jaun- Grade Characteristics
dice to encephalopathy and sub-acute liver failure when
encephalopathy occurs within 5–12 weeks of the onset I Trivial lack of awareness
Euphoria or anxiety
251
of jaundice. This has not received universal acceptance Shortened attention span
with the terms fulminant and sub-fulminant hepatic Impaired performance of simple tests e.g. addition
failure still used in clinical practice. II Lethargy or apathy
ALF without preexisting liver disease can result from Subtle personality changes
drug reactions, toxins or viral infection, or from the Inappropriate behaviour
effect on inflammatory mediators released in response III Somnolence to semi-stupor, but unresponsive to
to tissue injury. Liver failure can also occur as an acute verbal stimuli
decompensation of chronic liver disease (acute-on- Confusion
Gross disorientation
chronic liver failure: AoCLF) or as an end-stage decom-
pensation in chronic liver failure. AoCLF can be IV Coma: unresponsive to verbal or painful stimuli
precipitated by bacterial or viral infection, bleeding or
intoxication, and results in the same clinical syndrome
as seen in ALF. 234
End-stage decompensation of chronic liver failure repre-
sents irreversible deterioration with inadequate residual which leads to the development of cerebral oedema.
function to maintain homeostasis, and liver transplanta- Ammonia levels also seem to be related to the disruption
tion is the only viable treatment (see later in the chapter). of neurotransmission, resulting in decreased cerebral
234,236,256
However, in AoCLF, the function of the residual liver cell function. In addition, reactive oxidative species
mass may be adequate to maintain hepatic homeostasis causing oxidative stress and inflammatory cytokine
if the precipitating event can be treated. 234,236 release have been suggested, and the exact pathophysio-
257
logy is yet to be fully elucidated.
Liver dysfunction is also a common consequence of criti-
cal illness, 252,253 and may be caused by inadequate perfu- Previously, hepatic encephalopathy has been classified
258
sion leading to ischaemic injury or as a result of the using the West Haven criteria, a four-stage scale accord-
inflammatory response in sepsis. Given the number of ing to the severity of clinical signs and symptoms (Table
234
drugs that critically ill patients receive, the possibility of 19.9). However, the West Haven system has poor sensitiv-
liver injury as a result of drug reactions and toxicity ity and no inherent metric component. For instance, for
should always be considered. patients with grades III–IV encephalopathy, the Glasgow
Coma Scale (GCS) is probably a more sensitive tool for
CONSEQUENCES OF LIVER FAILURE neurological assessment. 256 Accordingly, other grading
259,260
criteria have been proposed
but are yet to be vali-
The consequences of liver failure manifest as a syn- dated in large clinical trials.
drome of hepatic encephalopathy (HE), hepatorenal
syndrome (HRS), oesophageal and gastric varices, ascites, Hepatorenal Syndrome
respiratory compromise, haemodynamic instability, sus- Hepatorenal syndrome (HRS) is the development of
ceptibility to infection, coagulopathy and metabolic renal failure in patients with severe liver disease (acute or
derangement. 234,236,237,254
chronic), in the absence of any other identifiable cause
of renal dysfunction. 262 HRS that develops rapidly in the
Hepatic Encephalopathy setting of ALF or AoCLF is classified as type 1 HRS, while
Hepatic encephalopathy is a reversible neuropsychiatric type 2 HRS is slowly progressing and is usually associated
complication due to metabolic dysfunction associated with diuretic-resistant ascites. 262,263
with liver disease. 255 The cerebral effects of liver failure
may manifest as an altered sleep–wake cycle, mild The pathophysiological features of HRS appear to be
confusion/disorientation, asterixis (i.e. abnormal tremor, caused by an inflammatory response from the injured
especially in the hands) and coma. Patients with liver, resulting in upregulation of nitric oxide production
234,236,262,263
AoCLF may develop a mild degree of cerebral oedema, (a vasodilator) and splanchnic vasodilation.
while a differential feature of ALF is the risk of Splanchnic vasodilation results in redistribution of circu-
death from cerebral oedema and raised intracranial lating blood volume and a lowered mean arterial pres-
pressure. 256 sure. The reduction in perfusion pressure results in an
enhanced sympathetic nervous system response and local
The exact mechanisms responsible for the development renal autoregulatory responses. The net result of these
of hepatic encephalopathy are unknown, although raised effects is a reduction in renal blood flow and increased
ammonia levels resulting from the failure of the liver urea activity of the renin–angiotensin–aldosterone system,
cycle are thought to be central to the pathogenesis. The resulting in sodium (aldosterone) and water retention
raised ammonia levels disrupt the blood–brain barrier, (arginine vasopressin; see Chapter 18).

Gastrointestinal, Liver and Nutritional Alterations 519

circulation (low systemic vascular resistance and high
265
Practice tip cardiac output) seen in liver failure. Other factors, such
as pleural effusions or severe ascites, may impinge on
Avoid using lactate- or citrate-buffered substitution/dialysis ventilation.
fluid for renal replacement therapy in patients with liver dys-
function, as they will be unable to metabolise the lactate or Haemodynamic Instability, Susceptibility
citrate and will develop an increasing metabolic acidosis. to Infection, Coagulopathy and
Metabolic Derangement
Varices and Variceal Bleeding The hyperdynamic, low vascular resistance picture, similar
to that associated with sepsis, is seen in liver dysfunction.
The development of varices and variceal bleeding arises This probably results from the production of vasodilator
from portal hypertension. This manifests when blood substances (nitric oxide) from the inflammatory response
flowing from an area of high pressure (i.e. the cirrhotic of the injured liver cells. 234 Sepsis may also be a complica-
liver) to areas of lower pressure (i.e. the collateral circula- tion of liver dysfunction because of the failure of the liver
tion, involving veins of the oesophagus, spleen, intestines to produce acute-phase proteins and the impaired func-
and stomach), causes the tiny, thin-walled vessels to tion of Kupffer cells. 237
become engorged and dilated, forming varices that are
vulnerable to gastric secretions, resulting in rupture and Hepatocyte damage leads to a decreased production of
haemorrhage. 241,264 Variceal haemorrhage is a major cause the majority of clotting factors and, therefore, haemosta-
of acute decompensation and a reason for admission to sis. Therefore, the risk of bleeding is elevated. 266 Disor-
the ICU. It is an acute clinical event characterised by dered metabolic function and failure of synthetic function
severe gastrointestinal haemorrhage presenting as hae- can manifest as unstable blood glucose levels.
matemesis, with or without melaena, and haemodynamic
instability (tachycardia and hypotension). 241,264 Practice tip

Patients in ALF or AoCLF are at risk of hypoglycaemia, and
Practice tip blood glucose levels should be measured routinely.
Coagulation state and the risk of trauma to varices should be
carefully considered before insertion of nasogastric or orogas- NURSING PRACTICE
tric tubes, or suctioning of the upper airway. Trauma may result The management of patients with liver dysfunction is
in epistaxis with significant bleeding or variceal bleeding. complex and involves multisystem organ support, and
as such requires a multidisciplinary and collaborative
Ascites approach to patient care.
Ascites is usually present in the patients with chronic liver INDEPENDENT PRACTICE
disease. In the ICU setting it becomes an issue when Early signs of the patient presenting with ALF are malaise,
abdominal pressures rise, resulting in reduced cardiac loss of appetite, fatigue, nausea, jaundice, bruising, bleed-
output due to decreased venous return and renal impair- ing, inflamed/enlarged liver, possibly epigastric and right-
ment. Pressure on the diaphragm causes loss of lung upper-quadrant pain, high or low blood glucose levels
volume, resulting in increased work of breathing and (which require monitoring, at least every 4 hours; patients
compromised oxygenation. may require insulin infusion or 10–50% dextrose infu-
sion), deranged liver function tests (LFTs) and fluctuating
GCS due to cerebral oedema. 237 If acute liver failure is
Practice tip suspected, admission to an ICU is recommended to
Patients with AoCLF may develop ascites, causing a rise in intra- monitor for further deterioration, and provide supportive
abdominal pressure (IAP). Raised IAP has negative effects on management and airway protection. The patient present-
work of breathing, cardiac preload and intra-abdominal organ ing with AoCLF will have similar symptoms but will
perfusion. IAP should be measured (see Chapter 23). present with other unique characteristics. Cirrhosis and
portal hypertension will often lead to oesophageal and
gastric varices, ascites, hepatorenal and hepatopulmonary
Respiratory Compromise syndrome, malnutrition, bone disease, sepsis, palmar ery-
Patients with liver failure may have poor oxygen exchange, thema, spider naevi and feminisation in males. 267
fluctuating GCS that requires intubation for airway pro- If liver failure is suspected, investigating ingestion of
tection and hepatopulmonary syndrome (HPS). HPS is hepatotoxic substances (paracetamol, steroids, ethanol),
found in 15–20% of patients with cirrhosis. 265 It is defined oral or intravenous recreational drug use, and any recent
as pulmonary microvascular dilation resulting in impaired travel (viral infections) is required.
oxygenation, and it is generally assumed that vascular
production of vasodilators, specifically nitric oxide, Neurological Considerations
underlies the vasodilation in HPS. It has also been Cerebral oedema is present in 80% of patients with
hypothesised that the mechanisms that trigger HPS are grade IV encephalopathy and is the leading cause of
the same as those that result in the hyperdynamic death due to brain herniation. 268 Patients with cerebral

520 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 19.10 Testing and classifying liver function 269,273

Blood test Normal value Description
Alanine aminotransferase ALT: <35 U/L ● ALT and AST are enzymes that indicate liver cell damage; they are produced within the liver
(ALT) and aspartate AST: <40 U/L cells (hepatocytes) and leak out into the general circulation when the liver cells are damaged.
aminotransferase (AST) ● ALT is a more specific indication of liver inflammation.
● In acute liver injury, ALT and AST may be elevated to the high 100s, even 1000s, U/L.
● In chronic liver damage such as hepatitis or cirrhosis, there may be mild to moderate
elevation (100–300 U/L).
● ALT and AST are commonly used to measure the course of chronic hepatitis and the
response to treatments.
Alkaline phosphatase ALP: 25– ● These are enzymes that indicate obstruction to the biliary system.
(ALP) and gamma- 100 U/L ● They are produced in the liver, or within the larger bile channels outside the liver.
glutamyl-transpeptidase GGT: Males ● The GGT is used as the supplementary test to be sure that a rise in ALP is indeed coming
(GGT) <50 U/L from the liver or biliary tree.
Females
<30 U/L ● A rise in GGT but normal ALP may indicate liver enzyme changes induced by alcohol or
medications, causing no injury to the liver.
● ALP and GGT are commonly used to measure bile flow obstructions due to disorders such as
gallstones, a tumour blocking the common bile duct, biliary tree damage, alcoholic liver
disease or drug-induced hepatitis.
Bilirubin < 20 µmol/L Results from the breakdown of red blood cells. Thus bilirubin is protein-bound and circulates in
the blood in an unconjugated form. The liver processes bilirubin to a water-soluble
conjugated form that is excreted in the urine and faeces.
● Liver injury or cholestasis results in an elevated bilirubin level.
● Raised unconjugated bilirubin without an accompanying rise in conjugated bilirubin is
consistent with red blood cell destruction (haemolysis).
● Raised bilirubin levels result in jaundice.
● In cases of chronic liver disease, bilirubin levels usually remain normal until significant
damage occurs and cirrhosis develops.
● In cases of ALF, bilirubin levels will rise rapidly and result in marked jaundice; the degree of
rise is indicative of the severity of illness.
Albumin 32–45 g/L ● Albumin is a major protein formed by the liver; it provides a gauge of liver synthetic function
(i.e. albumin levels are lowered in liver disease).
Clinical assessment: Model Developed to predict mortality risk and assess disease severity in patients with cirrhosis. The
for end-stage liver score is calculated from a mathematical model using values of bilirubin, INR, creatinine, and
disease (MELD) score aetiology (whether cholestatic or alcoholic).



oedema and raised intracranial pressure due to ALF are Transplantation). 270,271 These tests have been summarised
managed primarily as patients with acute head injury in Table 19.10. 253,272
(see Chapter 17).
Treatment
COLLABORATIVE PRACTICE ALF or AoCLF therapy often involves the support and

The collaborative management of ALF focuses on provid- treatment of the consequences of liver failure, such as
ing interim support until either hepatic recovery occurs sepsis, encephalopathy, renal failure and coagulopathy
or liver transplantation is undertaken. (see Table 19.11). One specific support therapy that may
be used to prevent further liver cell injury is administra-
Assessment of Liver Function tion of N-acetylcysteine (NAC), a glutathione donor that
Patients presenting with ALF require a careful history to acts to replenish liver cellular stores of this scavenger of
establish the cause of liver injury. The well-known signs toxic oxygen free-radicals. Inflammation, the accumula-
of chronic liver disease (e.g. palmar erythema, spider tion of bile acids, and ischaemia/reperfusion results in
naevi and ascites) may not be present. Biochemical and the build-up of oxygen free-radicals, which can induce
237
haematological tests determine whether liver cell injury hepatic necrosis if not controlled.
is occurring, with liver synthesis and clearance functions Oesophageal balloon tamponade and
assessed by albumin level and prothrombin time, and
bilirubin level respectively. 269 These measures have been transjugular intrahepatic portosystemic
incorporated into a scoring system to determine stent/shunt
liver dysfunction and prognostic information for liver There are two types of balloon tamponade devices available
transplantation suitability (model for end-stage liver on the market: the Sengstaken-Blakemore tube (see Figure
disease [MELD], see later in this chapter under 19.1) and the Linton tube. The Sengstaken-Blakemore is a

Gastrointestinal, Liver and Nutritional Alterations 521



TABLE 19.11 Treatment of liver failure complications

Condition Treatment
Hepatic encephalopathy ● Treatment revolves around general supportive therapy until liver function recovers or liver transplant is
undertaken. 236,256
● Cerebral oedema and raised intracranial pressure are treated as for an acute head injury (see Ch 17).
● Reduce production and absorption of ammonia by preventing/controlling upper gastrointestinal bleeding and
gastrointestinal administration of non-adsorbable disaccharides such as lactulose or lactitol to remove protein
derived from dietary intake or bleeding. 274
Hepatorenal syndrome ● Liver transplant is the primary treatment for type 1 HRS in patients with cirrhosis.
(HRS) ● If transplant is contraindicated or delayed, vasocontrictors (e.g. terlipressin) may be effective in constricting the
dilated splanchnic arterial bed, thus improving renal perfusion pressure and renal function. Vasocontrictors may
be given in association with intravenous albumin in order to increase intravascular volume. 262,263
Variceal bleeding A successful outcome, as in all cases of gastrointestinal haemorrhage, hinges on prompt resuscitation,
haemodynamic support, and correction of haemostatic dysfunction, preferably in the intensive care setting.
● The patient is intubated for airway protection.
● Adequate IV access in inserted, preferably large, wide-bore cannulas for rapid fluid resuscitation.
● Haemodynamic instability is corrected with volume expanders initially and then blood products.
• The source of bleeding is identified by endoscope, and varices are banded/ligated (latex bands placed around the
varices to ‘strangle’ the vessel), or sclerotherapy or diathermy (heat used to cauterise bleeding vessel) is used.
● Terlipressin and octreotide infusions may be used to reduce portal circulation pressure.
● If bleeding is uncontrollable, a balloon tamponade device is inserted.
Ascites Salt and water restrictions along with diuretic therapy are methods that have been used to control ascites in the
preliminary phases of end-stage liver failure; however, in the intensive care setting these measures are impractical
and usually unsuccessful.
● Paracentesis is very effective at reducing ascites and is a simple procedure to remove fluid and an aid in diagnosis.
● Correction of coagulopathy or thrombocytopenia should be considered when the INR is greater than 2.5 or the
platelet count markedly reduced.
● Paracentesis may aid in determining the cause of ascites (ascites-serum albumin gradient, ascitic cytology,
microscopy and culture for acid-fast bacilli, chylous ascites) and in establishing or excluding primary or secondary
peritonitis in patients with ascites (ascitic WCC and neutrophil count, culture).
● Litres of ascites are normally removed, and the volume is replaced with IV concentrated albumin to prevent fluid
shifts and hypotension.
● Mean arterial pressures, central venous pressures, heart rate and urine output are carefully monitored during the
procedure. For every litre of ascites removed, 6–8 g albumin is infused. 275




four-lumen tube with oesophageal and gastric balloons, ● ensuring that correct traction is maintained, with
and oesophageal and gastric aspiration ports. The benefit regular checking of tube migration and checking posi-
of this tube is that direct pressure can be applied on gastric tion at nares/lips at regular intervals (4/24 hours).
and oesophageal varices by balloon inflation and trac- Tamponade is generally maintained for 24–48 hours,
tion. 276 The Linton tube has one lumen for inflation of the then traction is removed and the balloon deflated to
pear-shaped gastric balloon and two additional lumens for assess for further bleeding. If the patient is
oesophageal and gastric aspiration.
stabilised, endoscopy can be performed. If bleeding
Prior to insertion (oral or nasal), balloons are lubricated, persists, the balloon(s) is/are reinflated and traction
checked for leakage, and the distance to the cardio- reapplied. 264,276
oesophageal junction is estimated (nose to ear, then to
xiphisternum). Once inserted, the gastric balloon is Once the patient has been stabilised, a transjugular intra-
inflated with 50 mL air and pulled back until resistance hepatic portosystemic stent/shunt (TIPS) may be con-
is felt. Position (lying compressed against the cardio- sidered to control variceal haemorrhage. TIPS is a metal
oesophageal junction) is confirmed by X-ray. Then the expandable stent inserted to decompress the portal
277
gastric balloon is inflated according to the manufacturer’s venous system.
instructions and traction is applied using a weight (500 Extracorporeal liver support
or 1000 mL IV fluid bag) attached to rope; traction is
applied via a pulley and IV pole at the foot of the bed. The aim of extracorporeal liver support therapy is to allow
Nursing care 276 of patients involves: time for liver recovery or to provide support until a
234
liver transplant is possible. Either biological or non-
● sedation for comfort biological systems are available for liver support. Biologi-
● head of the bed raised at least 30 degrees to facilitate cal systems utilise pig hepatocytes or hepatoma cells to
gastric emptying and prevent aspiration achieve removal of toxins, 234 but this requires complex
● ensuring that gastric/oesophageal ports are on free technical support in specialist centres. Non-biological
drainage, with regular monitoring of type and amount systems are similar to renal replacement circuits, and use
of drainage albumin as a dialysis medium or dialyse against an

522 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

reduced overall hospital length of stay. Survival rates of
all patients who have undergone liver transplantation
exceed 80% at 5 years, 283 with children having superior
survival rates to adults. 282
INDICATIONS FOR TRANSPLANTATION
oesophageal
balloon lumen Indications for liver transplantation are patients with
severe liver disease in whom alternative treatments have
been exhausted. Categories consist of acute liver failure,
end-stage liver disease, metabolic liver disease and
oesophageal and primary liver cancer. 284 Timing and patient selection is of
gastric aspiration critical importance, as this has contributed to the success
lumens of transplantation. Re-transplantation for any disorder is
considered only in patients with acceptable predicted
gastric balloon lumen survival. 283
CONTRAINDICATIONS FOR
oesophageal balloon
TRANSPLANTATION
Generally, Australian centres set upper age limits of
around 65 years for liver transplantation, but occasion-
gastric balloon ally older patients are considered. Patients with extra-
hepatic malignancy and uncontrolled systemic infection
(contraindication to high-dose immunosuppressive
therapy) are unsuitable for transplantation. In addition,
FIGURE 19.1 Sengstaken-Blakemore tube.
patients with alcoholic liver disease with social instability
and patients with inadequate or absent social support are
relative contradictions due to increased risk of non-
activated charcoal medium as a mechanism for toxin adherence to immunosuppressive therapy. 283
removal and liver support. 278

Albumin plays a key role as a transporter of substances RECIPIENT SELECTION
that are toxic in the unbound state and normally cleared
by the liver. Albumin binds to a number of substances The model for end-stage liver disease (MELD) and paedi-
that accumulate in liver failure and have been implicated atric end-stage liver disease (PELD) scoring systems are
in the development of the hepatorenal syndrome, hepatic used for liver transplantation eligibility in Australia and
283,285
encephalopathy, haemodynamic instability, ongoing New Zealand. The MELD score is a mathematical
liver injury and inhibition of liver cell regeneration. The model that includes bilirubin, creatinine and INR which
286
use of albumin as a dialysis medium to clear albumin- was originally devised to predict survival after TIPS. The
bound toxins can also be used in extracorporeal therapy. MELD score is the best predictor of pre-transplant mortal-
ity, and eliminates the subjectiveness of the CTP score
regarding the presence and degree of ascites and hepatic
LIVER TRANSPLANTATION encephalopathy. 285,287,288
Liver transplantation is the definitive treatment for Once the need for transplantation is established, the deci-
patients suffering acute and chronic end-stage liver failure sion to allocate a donor liver to a patient is based on
when other supportive critical care therapies have been donor and recipient blood group; donor size and size of
exhausted. 250,279 recipient; suitability of donor liver for splitting; severity
of disease; matching of functional status of donor with
In Australia, the first liver transplant was undertaken in severity of liver disease; and hepatitis B and C status of
Brisbane in 1985. 280 Liver transplantation commenced in donor and recipient. 283
281
1998 at Auckland Hospital in New Zealand. Between
1985 and December 2009, 3533 orthotopic liver trans- Extensive testing and consultation is part of the liver
plants were performed in Australia and New Zealand on transplant process. Clinical consultation occurs with hep-
3277 patients. 282 There are six liver transplant units in atologists, clinical nurse consultants, social workers, dieti-
Australia and New Zealand: the Royal Prince Alfred and tians, psychiatrists, psychologists and drug and alcohol
Children’s Hospitals, Sydney; the Austin and Royal professionals if required.
Children’s Hospitals, Melbourne; the Princess Alexandra
and Royal Children’s Hospitals, Brisbane; Flinders SURGICAL TECHNIQUES
Medical Centre, Adelaide; Sir Charles Gairdner Hospital, The common liver transplant techniques – orthotopic
Perth; and Auckland Hospital, New Zealand. 282
(using either portal bypass or a piggyback approach),
Surgical refinement and postoperative management of split-liver or adult living donor transplantation – are
liver transplantation has reduced time in critical care and discussed below.

Gastrointestinal, Liver and Nutritional Alterations 523

Orthotopic Liver Transplantation Within the first few months, a split liver will regenerate
Orthotopic liver transplantation (OLTx) is the replace- until it is a full-sized liver; in children it also grows and
ment of the diseased liver. Current surgery times are now develops at the same rate as the children. This technique
6–8 hours, having previously been 12–18 hours. This has significantly reduced the number of children waiting
reduction in surgical time and improvement in technique for liver transplantation, although little impact has been
273,296
has led to reductions in intra- and postoperative made on adult waiting lists.
complications.
Adult Living Donor Liver Transplantation
Two main techniques are used for OLTx: portal bypass or
the piggyback technique. Portal bypass occurs where an Living donor liver transplantation (LDLT) is an estab-
internal temporary portocaval shunt or external veno- lished option for paediatric patients with end-stage
297
venous bypass is used. 289-291 In the piggyback technique, liver disease. This technique involves removal of
the recipient’s inferior vena cava (IVC) is left and the the left lobe from the live donor, usually the recipient’s
donor IVC is piggybacked onto the recipient’s IVC. The parent, which is then transplanted into the child. It is a
advantages of this technique include haemodynamic relatively straightforward procedure, with little risk to the
297,298
stability during the anhepatic phase, reduced operating donor.
times and reduced use of blood products, enabling a Adult-to-adult LDLT involves transplantation of the right
292
shorter length of hospital stay. The use of T tubes, to lobe of the liver from a donor to an adult recipient, offer-
monitor bile outflow, leaks, stenosis, and to provide ing hope to patients with end stage liver disease (ESLD).
direct access to the biliary system to perform controlled The operation has been performed with some success,
cholangiograms and interventional radiographic proce- although there are significant risks to the donor, includ-
dures 293,294 are now not common. It has been shown that ing death and morbidity. 298
there were fewer biliary complications and costs were
reduced (there were fewer radiographic interventions) POSTOPERATIVE MANAGEMENT
without insertion of a T tube. 295
The postoperative management of liver transplant
patients is not dissimilar to other critical care surgical
Split-liver Transplantation patients yet the combination of hepatic-specific
The disparity between the increasing number of people issues and immunosuppressive therapy can make the
on transplant waiting lists and the shortage of donor management challenging.
livers available has led to several innovative strategies.
Split-liver transplantation occurs when the cadaver organ Initial Nursing Considerations
is divided for two recipients, with the larger right segment The initial postoperative care of liver transplant patients
going to an adult and the smaller left lobe to a child (see on return to critical care involves stabilisation, manage-
Figure 19.2). 273,296 The complication rate is higher in split- ment of positive pressure ventilation, continuous haemo-
liver than whole-liver transplants due to biliary leaks and dynamic monitoring and physical assessment, as with all
anastomosis strictures. The risk of complications and the critically ill surgical patients. It is common for patients to
potential for small-sized grafts are taken into consider- be hypertensive post-surgery, displaying systolic blood
ation when selecting a recipient patient for transplant. pressure (SBP) above 160 mmHg with a mean arterial
Furthermore, not all donor livers are suitable for splitting. pressure (MAP) of 110 mmHg. Aggressive treatment is
required due to the risk of stroke, which is compounded
by low platelet counts and abnormal clotting. Once pain
is controlled and excluded as a cause of hypertension,
clonidine or hydralazine is considered. Oliguria is
commonly related to intraoperative fluid losses and
fluid shifts.
Once initial stabilisation is achieved, treatment is gov-
erned by clinical progress. Patients who have uncompli-
cated surgery and return to critical care in a stable
condition with good graft function are rapidly weaned
from mechanical ventilation within 12–24 hours. Typi-
cally, the critical care stay for a routine postoperative liver
transplantation does not exceed 24–48 hours; as long as
physiological systems are maintained, discharge to the
ward can be anticipated. An abdominal CT scan may be
considered at 7–10 days postoperatively or when clini-
cally indicated.
The initial postoperative care is similar for all liver trans-
plant patients. However, progress, stability and discharge
FIGURE 19.2 Split-liver transplantation (Courtesy Australian National from critical care can be affected by the patient’s preop-
Liver Transplantation Unit). erative condition and severity of liver failure. The unique

524 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

pathophysiology inherent in the end-stage liver failure often experience bibasal collapse and consolidation, and
patient will predispose to varying effects on coagulopathy are prone to infection. Incentive spirometry, chest phys-
and cardiopulmonary, neurological, haemodynamic and iotherapy, early mobilisation and adequate pain relief are
metabolic functions. 299,300 These issues are discussed recommended. 300
below.
Gastrointestinal
Blood loss and coagulopathy Patients with end-stage liver disease often have malnutri-
The major risk during and post-surgery is massive blood tion and bone disease, which may influence post-operative
loss, due to a combination of factors. The surgical process management. Fluid overload and ascites can quite often
itself involves anastomosis of major arteries and veins, mask signs of malnutrition. Early nutrition is imperative
usually in the setting of significant portal hypertension, in the postoperative period. If caloric intake is inade-
predisposing the patient to bleeding and hypovolaemia quate, consultation with a dietitian will assist with enteral
291
during surgery and anastomotic leaks post-surgery. supplementation. Total parenteral nutrition is rarely
Patients with ESLD will also be coagulopathic from required. 304
hepatic synthetic dysfunction, leading to failure of syn-
thetic clotting factors. Correction of coagulopathy with Renal
blood products such as FFP, platelets, cryoprecipitate and Renal dysfunction is a significant posttransplantation
factor VIIa may control minor postoperative bleeding, problem. Risk factors include preexisting renal disease
but if bleeding continues an exploratory laparotomy may or hepatorenal syndrome, intraoperative hypotension,
be required. Conversely, it is not desirable to overcorrect extensive transfusion of blood products, nephrotoxic
coagulopathy, due to the potential for vascular complica- drugs such as cyclosporin and tacrolimus, sepsis, and
305
tions such as hepatic artery thrombosis. Careful monitor- graft dysfunction. Hepatorenal syndrome is reversible
ing is required to identify and manage hypotension, post-transplantation. Patients who are receiving renal
tachycardia, excessive blood loss from drains, falling hae- support such as CRRT usually require continuation of
moglobin, abdominal swelling and oozing from inser- renal support postoperatively for a period of time until
tion sites. Thrombocytopenia is a common postoperative recovery of kidney function is evident (see Chapter 18).
problem, with platelet counts often falling in the first
week post-transplant. If platelet counts are low, a platelet Graft dysfunction and rejection
transfusion may be necessary, especially prior to removal Acute graft rejection was the most challenging obstacle in
of drains, lines, cannulae and sheaths.
the early years of transplantation, but with the develop-
ment of current immunosuppressive therapy, acute
Cardiovascular rejection can be avoided, resulting in improved success
306
Haemodynamic instability in the early postoperative rates of transplantation. Immunosuppressive therapy is
period may be due to hypovolaemia or haemorrhage. commenced intraoperatively with a high-dose steroid
Treatment includes fluid boluses to increase preload and such as methylprednisolone and antibiotic (ticarcillin).
301
the initiation of inotropes may be necessary. The patient Patients are then placed on a triple-therapy regimen
with ESLD may present with a hyperdynamic profile: consisting of steroids such as methylprednisolone and,
high cardiac output, low systemic vascular resistance, later, prednisone, azathioprine and either tacrolimus or
302
and low mean arterial pressure, although this usually cyclosporin. 306,307
reverses one week after transplantation. 300
Allograft dysfunction occurs within 48 hours of trans-
plantation, and is characterised by varying degrees of
Neurological coma, renal failure, worsening coagulopathy, poor bile
The most frequent neurological complications relate to production and marked elevation in the liver enzymes
patients with preexisting encephalopathy and seizures. In (AST, ALT) and worsening acidosis. The cause of allograft
ALF patients, cerebral oedema with raised intracranial dysfunction is not always known; possible causes are
pressure (ICP) is common, and after liver transplanta- injury to the liver, either before or during the donor
tion, cerebral oedema may take up to 48 hours to subside. operation procedure, ischaemic-reperfusion injury or
Therefore, continuation of preoperative measures to graft stenosis. Acute rejection is generally evident in the
reduce ICP are necessary. These include the head of the second week posttransplant, and is generally suspected
bed at 30 degrees, head, neck and body alignment, ensur- with a rise in liver enzymes, a decline in bile quality
ing that endotracheal tapes are not constrictive, aiding (accessible only if a T tube is present), occasional fever
venous return and preventing cerebral congestion, reduc- and tachycardia. 308
ing neurological stimuli and timing activities to prevent
spikes in ICP (see Chapter 17). 302,303 Primary graft non-function is defined as failure of the
graft to function in the first postoperative week. It is
Respiratory manifested by failure to regain consciousness, sustained
elevated transaminases, increasing coagulopathy, acidosis
Preexisting pulmonary complications associated with and poor bile production. Causes include massive
liver disease can affect postoperative recovery and need haemorrhagic necrosis, ischaemia-reperfusion injury and
to be considered when weaning ventilation and main- hepatic artery thrombosis. It may be difficult to distin-
taining adequate oxygenation. Patients posttransplant guish allograft dysfunction, which may recover, from

Gastrointestinal, Liver and Nutritional Alterations 525

primary graft non-function, which will not recover, and those studies that appear to have used similar methods,
the only solution is retransplant. 308 has continued to fuel the debate on tight glycaemic
control with some experts urging caution and others
Confirmation of rejection is by liver biopsy but this is not
always possible if the patient is coagulopathic; if the diag- seeing tight glycaemic control as a marker of quality prac-
322
nosis is positive, rejection is treated with high-dose steroid tice. The discrepancies in these studies have been attrib-
pulse therapy, followed by reducing doses of oral predni- uted to many factors including the variability in target
sone. The majority of rejection episodes respond well to ranges for blood glucose, methods of blood glucose mea-
pulse steroid therapy. Previously, treatment with a course surement, difficulty for some studies to achieve separa-
of antilymphocyte (e.g. monoclonal antilymphocyte tion of the treatment and control groups, compliance
globulin, OKT3) 306,307 was recommended, but has now with the therapy, and employment of different nutri-
323
been shown to increase the risk of hepatitis development tional strategies.
in patients with transplants for hepatitis C infections. 309 Our knowledge of tight glycaemic control in the context
of critical illness continues to develop, however, the
Late Complications definitive target for blood glucose in tight glycaemic
Readmission to critical care after liver transplantation is control remains unclear. Nevertheless it is recognised that
not uncommon, with 1 in 5 patients returning due to hyperglycaemia is associated with poorer outcomes and
complications. The most common factors include cardio- therefore should not be neglected. The implications for
pulmonary dysfunction from infection or fluid overload, nursing practice of implementing tight glycaemic control
respiratory failure from collapse and consolidation, in critical care practice are considerable. Incorporating
tachypnoea, recipient age, preoperative liver function, tight glycaemic control into a dynamic setting where
bilirubin, the amount of blood products administered patient acuity regularly and rapidly fluctuates can be chal-
intraoperatively, graft dysfunction, severe sepsis and post- lenging, and consequently requires critical care nurses to
operative surgical complications such as bleeding and have the requisite knowledge and expertise to manage
310
biliary anastomotic leaks. Outcomes are affected by this complex therapy.
intraoperative and postoperative complications, renal
failure, advanced liver disease and malnutrition. 311 Practice tip
GLYCAEMIC CONTROL IN The use of intravenous insulin for tight glycaemic control can
CRITICAL ILLNESS contribute to rapidly changing blood glucose levels therefore
vigilant monitoring is required.
Hyperglycaemia and increased insulin resistance are char-
acteristics of the stress response and activation of the Of particular importance when implementing tight
sympathetic nervous system: adrenal and hypothalamic– glycaemic control, is monitoring for hypoglycaemia.
312
pituitary–adrenal (HPA) axis responses to critical illness. Two large clinical trials of tight glycaemic control –
Hyperglycaemia has been considered a beneficial adap- NICE-SUGAR and the COIITSS Study 324 – reported
314
tive response to stress to provide energy substrate to the reasonably high rates of hypoglycaemia (6.8% and 16.4%
313
organs involved in the ‘fight or flight’ response. respectively), highlighting the need for vigilance in assess-
However, there is some, although inconsistent, evidence ing blood sugar levels. The time and frequency of blood
of the association of hyperglycaemia with high mortality glucose measurement that may be required for some
and morbidity. 313-317 Hyperglycaemia has been associated patients may impact on the provision of patient care, and
with: poor wound healing and higher rates of infection the inability to perform the testing as often as required
after surgery in diabetic patients; higher risk of death after may potentially contribute to underdetection of hypogly-
myocardial infarction in diabetic and non-diabetic caemia. Another potentially important factor that
patients; and poor outcomes after stroke. 313,318,319
may contribute to underdetection of hypoglycaemia is
fatigue in nurses caring for the critically ill. Louie and
Practice tip colleagues. 325 reported the results of a single-centre study
that found the increased number of antecedent shifts
If blood glucose is being maintained at normoglycaemic levels, worked by bedside nurses was associated with an
there is an increased risk of hypoglycaemia. The signs of hypo- increased incidence of hypoglycaemia.
glycaemia are altered mental state, sympathetic stimulation
(tachycardia, sweating) and, in extreme cases, fitting. The validity of blood glucose measurement is also an
important consideration. Many of the studies to date
have measured blood glucose sampled from arterial,
The complexity of the physiological processes associated venous and capillary blood. The use of capillary blood in
with hyperglycaemia in critical illness and the sophisti- testing blood glucose may be problematic, particularly in
cated research required to generate valid information those patients for whom hypoperfusion is an issue. 326-329
renders clinical decision-making related to glycaemic Techniques to measure blood glucose include point-of-
control challenging. Since the first landmark study of care testing meters, blood gas analysers and formal labo-
320
glycaemic control in the critically ill, there have been ratory testing. Formal laboratory testing is considered
at least 26 randomised controlled trials investigating tight ‘gold standard’ for blood glucose measurement although
321
glycaemic control. Contradictory results, even from the delay in receiving has resulted in point-of-care testing

526 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

330
meters being common in clinical practice. An impor- pathological consequences of extreme dehydration.
tant consideration with formal blood testing is the poten- Unlike DKA, where there is insufficient insulin, in HHNS
tial drop in glucose concentration of up to 6% within the insulin excretion is maintained, so lipolysis and keto-
331
first hour after the blood is taken, highlighting the acidosis do not feature. Although DKA and HHNS are
importance of ensuring blood specimens are delivered to considered separate entities, DKA and HHNS may coexist
the laboratory in a timely fashion and priority is given to in about a third of cases, especially among older
sample testing. patients. 342 Additionally, DKA is increasingly being iden-
tified in patients with type 2 diabetes. 343
Point-of-care testing of blood glucose is common in criti-
cal care setting. Research examining the measurement of PATHOPHYSIOLOGY
blood glucose using these devices is conflicting with
some studies reporting good performance of devices The metabolic profile seen in DKA is similar to that seen
while others report that the devices are unsatisfactory. A in the fasting state, with substrate utilisation shifting
problematic aspect of evaluating point-of-care devices is from glucose to fat in insulin-sensitive tissues (fat, liver,
the failure of many of these to conform 332 with quality muscles). The brain is insulin-insensitive, and requires a
guidelines for conducting and reporting glucose monitor continuous supply of glucose to support metabolism
evaluation studies. 333,334 even in a fasting state or DKA. 344
It is clear that hyperglycaemia should be avoided, however, Inadequate production (or administration) of insulin to
the inconsistencies in published studies mean that an meet metabolic need (or a rise in metabolic demand
agreed specified target for blood glucose in the critically resulting from the stress of infection, trauma or surgery,
323
ill patient population is difficult to achieve. The optimal for instance) is associated with a rise in the secretion of
target blood glucose level is unknown and may differ the counterregulatory hormones glucagon, the catechol-
depending on the patient’s clinical presentation. 335 Rec- amines and cortisol. 344 The effects of the counterregula-
ommendations for patients with sepsis suggest that blood tory hormones are presented in Box 19.1.
glucose levels be kept lower than 180 mg/dL with a goal Hyperglycaemia results from increased gluconeogenesis
blood glucose approximating 150 mg/dL. 336 (glucose production from precursors other than carbo-
hydrates, e.g. amino acids), the conversion of glycogen
INCIDENCE OF DIABETES stores to glucose (glycogenolysis) and the reduced uptake
IN AUSTRALASIA of glucose resulting from insulin deficiency. 344 Free fatty
acids (FFAs) and glycerol are produced by the break-
Diabetes is known to cause substantial morbidity and down of triglycerides that results from increased cate-
mortality in Australia. The prevalence of diabetes in Aus- cholamine secretion. 344 Metabolism of FFA results in
tralia is rising and follows a global trend. 337 Reasons for accumulation of ketone bodies or ketoacids (acetone,
this include an increase in the rates of obesity, physical beta-hydroxybutyrate, acetoacetate). 344 These compensa-
inactivity, the ageing population, better detection of dia- tory mechanisms are ultimately responsible for the patho-
betes and longer survival of affected individuals. 338,339 In logical effects seen in DKA (see Table 19.12). The
2004–05, the prevalence of diagnosed diabetes among pathophysiology of DKA is illustrated in Figure 19.3.
Australians was 3.6%. 337 The rate of diabetes generally
increased with age for both males and females, although NURSING PRACTICE
declining slightly for both sexes at age 75 years and over. Management of HHNS is similar to that for DKA, and
Males had higher rates of diabetes than females at ages includes respiratory support, fluid replacement,
45–54 years, 65–74 years and 75 years and over, and insulin treatment to turn off ketogenesis and the
ranged from 0.8% vs 0.7% (0–44 years) to 16.3% vs accompanying metabolic derangement, electrolyte
11.7% (65–74 years). New Zealand is experiencing a dia-
betes epidemic that has the biggest impact in the Māori
and Pacific ethnic groups. The incidence of diabetes was
forecast to nearly double by 2011, and to be accompanied BOX 19.1 Effects of counterregulatory
by a rise in mortality. 340 hormones in DKA 345,346

DIABETIC KETOACIDOSIS ● Catecholamines:
● Promote lipolysis, resulting in the production of FFA and
Diabetic ketoacidosis (DKA) is a metabolic derangement glycerol; FFA and glycerol used as precursors for
resulting from a relative or absolute insulin deficiency, gluconeogenesis
characterised by hyperglycaemia (>11.1 mmol/L), meta- ● Glucagon:
bolic acidosis (pH <7.3) and ketosis (raised blood ketone ● Stimulates gluconeogenesis
bodies or ketonuria). It is usually precipitated, in insulin- ● Cortisol:
and non-insulin-dependent diabetics, by infection or the ● Promotes lipolysis
omission (or inadequate dosing) of insulin. It may also ● Promotes protein breakdown and release of amino acids
341
be the cause of the first presentation in new-onset diabe- ● Promotes hepatic gluconeogenesis
tes. Hyperglycaemic hyperosmolar non-ketotic state
(HHNS) is seen more often in older patients with type 2 DKA = diabetic ketoacidosis; FFA = free fatty acids
diabetes, and is characterised by hyperglycaemia and the

Gastrointestinal, Liver and Nutritional Alterations 527



TABLE 19.12 Pathological effects of diabetic ketoacidosis (DKA)

Mechanism Action
Cellular dehydration and ● Hyperglycaemia increases the extracellular fluid osmolality and results in water movement from the cell.
intravascular volume ● Osmotic diuresis results from obligatory excretion of glucose in the urine.
depletion ● Osmotic diuresis results in reduction of total body water and severe dehydration.
Metabolic acidosis ● Ketoacids are fully dissociated at physiological pH (strong acids). Because of the complete dissociation,
acetoacetate and beta-hydroxybutyrate are strong ions (anions). 345
● The metabolic acidosis is explained by extracellular (and intracellular) buffering of the dissociated H , resulting
+
in a decrease in bicarbonate. Alternatively, the acidosis can be explained by accumulation of strong anions
166
(acetoacetate and beta-hydroxybutyrate) with resulting reduction of the strong ion difference, causing an
+
increased H dissociation from plasma water and thus a metabolic acidosis. 347,348
● The presence of ketone bodies widens the anion gap, strong ion gap and base excess gap. These ‘gaps’ can be
used to assess the degree of ketonaemia. As ketosis resolves, an acidosis caused by high chloride relative to
sodium levels is often seen and probably results from administration of normal saline in the initial
resuscitation, especially in the setting of decreased renal function where the ability to excrete chloride is
reduced.
Electrolyte imbalances ● The osmotic diuresis results in potassium, phosphate and magnesium loss.
● Total body potassium losses are particularly significant, as potassium shifts from the intracellular to the
extracellular space in concert with the osmotically driven water shift. Acidosis and lack of insulin exacerbates
the potassium shift. The final pathway for potassium loss is via the urine. 345







Insulin deficiency
(relative or absolute)


Decreased glucose
uptake Counterregulatory
hormones
Hyperglycaemia
Increased protein Increased lipolysis
catabolism Increased FFA
Increased serum
osmolality
Increased production Increased
of amino acids ketogenesis
Transcellular fluid
shift
Increased hepatic Increase in blood
glucose production ketone bodies
Cellular dehydration (gluconeogenesis)
Metabolic acidosis
Glycosuria

Ketonuria
Osmotic diuresis


Decreased extracellular Kussmaul breathing
Urinary electrolyte loss volume Nausea and vomiting


+
Decreased whole body K
Decreased phosphate
Decreased magnesium

FIGURE 19.3 Pathophysiology of diabetic ketoacidosis. 345,349