Basic Concepts of Fluid and Electrolyte Therapy
Basic Concepts of Fluid and Electrolyte Therapy
Basic Concepts of Fluid and Electrolyte Therapy
Lobo
Andrew J. P. Lewington
Simon P. Allison
Basic Concepts
of Fluid and
Electrolyte Therapy
Preface
Despite the fact that fluid and electrolyte preparations are the most
commonly prescribed medications in hospitals, a number of studies
have shown that the knowledge and practice of fluid and electrolyte
balance among young doctors is suboptimal, possibly due to inadequate teaching. This is responsible for errors in management, which
continue to cause avoidable morbidity and even mortality. It is not the
intention of the authors of this book to write a comprehensive textbook dealing with complex problems, but to provide a pocket book for
students, nurses and young doctors to help them to understand and
solve some of the most common practical problems they face in dayto-day hospital practice. The authors hope that it will also stimulate
them to pursue the subject in greater detail with further reading and
practical experience. In difficult cases, the young doctor should never
hesitate to ask for advice from senior and experienced colleagues.
Dileep N. Lobo
Andrew J. P. Lewington
Simon P. Allison
Foreword
This book, Basic Concepts of Fluid and Electrolyte Therapy, fills a long
felt need for an up to date pocket guide to the subject. Water and
electrolyte balance is crucial for body homeostasis and is one of the
most protected physiological mechanisms in the body. While we can
survive for months without food, without water intake we die very
quickly. Similarly the body has very strong mechanisms to control salt
and water balance, an understanding of which has major implications
in clinical practice.
Despite salt and water balance being so fundamental for homeostatic
control, knowledge and practice of fluid and electrolyte therapy has
been shown to be appallingly poor among many health care professionals. The results of such knowledge surveys have been reported by
the authors and were surely the reason why they felt the urge to write
this book.
Dileep Lobo, Andrew Lewington and Simon Allison are all well
renowned experts in this field covering different aspects of the topic:
surgery, renal medicine and clinical nutrition. This allows for a broad
approach to the concepts of fluid and electrolyte management and
gives the book sufficient depth to fulfil the basic needs of all medical
specialties.
The book covers the basics in physiology and pathophysiology, how to
assess fluid and electrolyte status, a clear overview of fluids used in
clinical practice and how to prescribe them, and then moves on to
describe and discuss some of the most common clinical problems.
The book is rich in tables and figures that help the reader grasp the
fundamentals, both physiological and pathophysiological. It contains
examples of how to address clinical situations and to monitor treatment, often with the help of simple cartoons and figures. The authors
have also done a fine job in explaining some of the more complex
issues involved, making this book a very useful read for everyone
involved in patient care, as well as for students in training for any
higher qualifications in the medical professions.
Whether you are a professional in medicine or a student, enjoy this
very interesting read, and make use of it in your practice!
Table of Contents
1. Normal Physiology and Anatomy of the Body Fluids
2. Definitions
23
29
41
49
57
7. Acid-Base Balance
61
8. Oliguria
73
79
95
101
113
117
Selected References
121
Index
129
ever, contains large anions such as protein and glycogen, which cannot escape and, therefore, draw in K+ ions to maintain electrical neutrality (Gibbs-Donnan equilibrium). These mechanisms ensure that
Na+ and its balancing anions, Cl and HCO3, are the mainstay of ECF
osmolality, and K+ has the corresponding function in the ICF.
Interstitial space
(14% body weight)
Na+ 140 mmol/l
K+ 4 mmol/l
Cell membrane
Intracellular space
(40% body weight)
Na+ 8 mmol/l
K+ 151 mmol/l
Capillary membrane
Intravascular space (6% body weight)
Na+ 140 mmol/l
K+ 4 mmol/l (Plasma) Red blood cells
The ECF is further divided into the intravascular (within the circulation) and the interstitial (extravascular fluid surrounding the cells)
fluid spaces. The intravascular space (blood volume = 5-7% of body
weight) has its own intracellular component in the form of red
(haematocrit = 40-45%) and white cells and an extracellular element
in the form of plasma (55-60% of total blood volume).
10
The intravascular and extravascular components of the ECF are separated by the capillary membrane, with its micropores, which allow
only a slow escape rate of albumin (5%/hr), which is then returned to
the circulation via the lymphatics at the same rate, thereby maintaining a steady state of equilibrium (Fig. 2). While the hydrostatic pressure within the circulation tends to drive fluid out, the oncotic pressure of the plasma proteins, e.g. albumin, draws fluid in and maintains
the relative constancy of the plasma volume as a proportion of the
ECF (Starling effect).
capil
lar
y
Transcapillary
escape rate
of Albumin
4-5% per hour
mbrane
me
ISS
IVS
Albumin
40 g/l
Lymph
Albumin 35 g/l
Th
or
ac
ic
du
ct
11
Gastric juice
1.5 L
Pancreatic
secretions
1.5-2 L
Bile
1L
8 L enter
proximal
jejunum
1.5 L cross
ileo-caecal
valve
0.15 L
excreted in
faeces
3 L cross
jejunum and
ileum
12
The external fluid and electrolyte balance between the body and its
environment is defined by the intake of fluid and electrolytes versus
the output from the kidneys, the gastrointestinal tract, and the skin
and lungs (insensible loss). Since the external and internal balances
may be disturbed by disease, it is important to understand normal
physiology in order to appreciate the disorders, which may occur in
patients.
External balance
Values for the normal daily intake and output of fluid and electrolytes
are shown in Tables 1 and 2. These are only an approximate guide and
may have to be modified in the presence of excessive losses, e.g. of
water and salt through increased sweating and insensible loss in hot
climates. They may also need to be modified in the presence of disease, e.g. gastroenteritis, which causes abnormal losses of fluid and
electrolyte from the GI tract (Fig. 3 and Table 3).
Output (ml)
1200
Urine
1000
900
Faeces
100
300
1500
13
Water
25-35 ml/kg/day
Sodium
0.9-1.2 mmol/kg/day
Potassium
1 mmol/kg/day
Na+ (mmol/l)
K+ (mmol/l)
Cl (mmol/l)
40
20
40
70-120
10
100
Bile
140
100
Pancreatic juice*
140
75
110-120
5-10
105
120
15
90
30-70
0-5
30-70
Secretion
Saliva
Gastric juice
Small intestine
Diarrhoea (adult)
Sweat
Intake
Under normal circumstances most of our fluid intake is oral, but
remember that all food contains some water and electrolytes and also
that water and CO2 are end products of the oxidation of foodstuffs to
produce energy. This metabolic water is a small but significant contribution to net intake. Our drinking behaviour is governed by the
sensation of thirst, which is triggered whenever our water balance is
14
Kidney: this is the main organ for regulating fluid and electrolyte
balance as well as excreting the waste products of metabolism, e.g.
urea. In this function, its activity is controlled by pressure and
osmotic sensors and the resulting changes in the secretion of hormones. The modest daily fluctuations in water and salt intake
cause small changes in plasma osmolality which trigger osmoreceptors. This in turn causes changes in thirst and also in renal
excretion of water and salt. If blood or ECF volumes are threatened
by abnormal losses, volume receptors are triggered (see below) and
override the osmoreceptors. In the presence of large volume
changes, therefore, the kidney is less able to adjust osmolality,
which can be important in some clinical situations.
Water
Organs, which sense the changes in osmolality of plasma
(osmoreceptors), are located in the hypothalamus and signal
the posterior pituitary gland to increase or decrease its secretion of vasopressin or antidiuretic hormone (ADH). Dilution of
the ECF, including plasma, by intake of water or fluid of osmolality lower than plasma, causes ADH secretion to fall, so that
the distal tubules of the renal glomeruli excrete more water and
produce a dilute urine (this dilution requires the permissive
effect of glucocorticoid upon the distal tubules and is, therefore, lost in adrenal insufficiency - one of the reasons for the
hyponatraemia of Addisons Disease). Conversely, dehydration
causes the ECF to become more concentrated, ADH secretion
rises and the renal tubules reabsorb more water, producing a
concentrated urine. In response to dehydration, the normal
kidney can concentrate urea in the urine up to a hundred-fold,
so that the normal daily production of urea during protein
metabolism can be excreted in as little as 500 ml of urine.
16
In the presence of water lack, the urine to plasma urea or osmolality ratio is, therefore, a measure of the kidneys concentrating
capacity. Age and disease can impair the renal concentrating
capacity so that a larger volume of urine is required in order to
excrete the same amount of waste products. Also if protein
catabolism increases due to a high protein intake or increased
catabolism, a larger volume of urine is needed to clear the
resulting increase in urea production.
To assess renal function, therefore, measurement of both urinary volume and concentration (osmolality) are important, and
the underlying metabolic circumstances taken into account. If
serum urea and creatinine concentrations are unchanged and
normal, then, urinary output over the previous 24 hours has
been sufficient, fluid intake has been adequate, and the urinary
volume obligatoire has been achieved.
Sodium
Since the integrity of the ECF volume and its proportion of the
total body water are largely dependent on the osmotic effect of
Na+ and its accompanying anions, it is important that the kidneys maintain Na+ balance within narrow limits. If salt depletion occurs, then the ECF, and with it the plasma volume, falls.
Pressure sensors in the circulation are then stimulated and
these excite renin secretion by the kidney. This, in turn, stimulates aldosterone secretion by the adrenal gland, which acts on
the renal tubules, causing them to reabsorb and conserve Na+.
17
Conversely, if the intake of Na+ is excessive, the renin-aldosterone system switches off, allowing more Na+ to be excreted,
until normal balance is restored. The mechanism for salt conservation is extremely efficient and the kidney can reduce the
concentration of Na+ in the urine to < 5 mmol/l. On the other
hand, even in health, we are slow to excrete an excess salt load,
possibly because our physiology has evolved in the context of a
low salt environment and not until modern times been exposed
to excessive salt intake. The response of atrial natriuretic peptide to fluid infusions seems to be related more to volume
(stretching of the right atrium) than sodium load per se.
The mechanism for maintaining sodium balance may become
disturbed in disease, leading to Na+ deficiency or, more commonly, to excessive sodium retention, with consequent oedema
and adverse clinical outcome.
Potassium (K+)
Although only a small proportion of the bodys K+ is in the
extracellular space, its concentration has to be maintained
within narrow limits (3.5-5.3 mmol/l) to avoid the risk of muscular dysfunction or potentially fatal cardiac events. This is
achieved by exchange of K+ in the renal tubules for Na+ or H+,
allowing more or less K+ to be excreted. In the presence of K+
deficiency, H+ ion reabsorption is impaired, leading to
hypokalaemic alkalosis.
18
Pathophysiology
Diseases such as gastroenteritis, diabetic ketoacidosis or Addisons
disease cause their own specific changes in fluid and electrolyte balance, but there are non-specific changes which occur in response to
any form of injury or inflammation, which have important implications for management, particularly of surgical patients.
Response to injury
In the 1930s, Cuthbertson described the metabolic changes, which
occur in response to injury (including surgery and sepsis), as an
increase in metabolic rate and protein breakdown to meet the
requirements for healing. These changes were later shown to be due
to neuroendocrine and cytokine changes and to occur in three phases.
The ebb or shock phase is brief and is modified by resuscitation. This
gives way to the flow or catabolic phase, the length and intensity of
which depends on the severity of injury and its complications. As
inflammation subsides, the convalescent anabolic phase of rehabilitation begins. In parallel with these metabolic changes there are
changes in water and electrolyte physiology. During the flow phase,
there is an increase in ADH and aldosterone secretion leading to
retention of salt and water with loss of potassium. These changes are
exacerbated by any reduction in blood or ECF volume.
The normal, if somewhat sluggish, ability to excrete an excess salt and
water load is further diminished , leading to ECF expansion and oedema. The response to injury also implies that oliguria is a normal
response to surgery, and does not necessarily indicate the need to
increase the administration of salt and water or plasma expanders
unless there are also indications of intravascular volume deficit, e.g.
from postoperative bleeding. Salt and water retention after injury can
be seen as natures way of trying to protect the ECF and circulating
19
volume at all costs. It also explains why sick patients can be so easily
overloaded with excessive salt and water administration during the
flow phase. Since water as well as salt is retained, it is also easy to
cause hyponatraemia by giving excess water or hypotonic fluid. It is
important, therefore, to administer crystalloids, not only in the correct
volume but also in the appropriate concentration. In the presence of
the response to injury, the kidneys are unable to correct for errors in
prescribing.
The convalescent phase of injury is not only characterised by the
return of anabolism but also by a returning capacity to excrete any
excess salt and water load that has been accumulated. These periods
have been termed the sodium retention phase and the sodium diuresis phase of injury.
Transcapillary escape rate of albumin
The response to injury, stress and sepsis also results in an increase in
the size of the pores in the capillary membrane and the transcapillary
escape rate of albumin increases from about 5%/h in health to 1315%/h. This phenomenon can last from several hours to days. Albumin
leaks out from the intravascular compartment into the interstitial
space and along with it, water and sodium are also drawn into the
interstitial space. This results in a net contraction of the intravascular
compartment and expansion of the interstitial space (Fig. 4). As the
return of albumin to the circulation via the lymphatics is unchanged,
the net result is an intravascular hypovolaemia with oedema.
20
capillary
ISS
Transcapillary
escape rate
increased
mbrane
me
IVS
Albumin
<40 g/l
Albumin
Water and Salt
ISS = Interstitial space
IVS = Intravascular space
Potassium
K+ losses after surgery, sepsis and trauma are not only secondary to
increased excretion, but also to protein and glycogen catabolism. As
intracellular protein is broken down and its constituent amino acids
are released from cells, so intracellular negative charges are lost and
K+, with its balancing positive charges, passes out into the ECF to be
excreted. In situations where catabolism is extreme and renal function is impaired, the outflow of K+ from the cells may exceed the
kidneys capacity to excrete it, causing dangerous hyperkalaemia.
Conversely, in the convalescent phase, as net intracellular protein and
glycogen anabolism is restored, the cells take up K+ again and the
patients potassium intake has to be increased or else hypokalaemia
will develop.
21
Conclusion
Appropriate fluid therapy depends on an understanding of the underlying physiology and pathophysiology and a consideration not only of
external but internal fluid balance.
22
2. Definitions
Much confusion in the diagnosis and treatment of fluid and electrolyte disorders is caused by loose and ambiguous terminology. The
term dehydration, for example, meaning lack of water, is often used
carelessly and imprecisely to include salt and water lack or, even more
confusingly, intravascular fluid depletion. We therefore make a plea
for the use of precise diagnostic terms, which indicate clearly the
deficit or excess and the treatment required.
Anabolism the synthesis of large molecules from small ones, e.g.
protein from amino acids or glycogen from glucose.
Catabolism the breakdown of large molecules into small ones, e.g.
protein to amino acids or glycogen to glucose.
Total body water (TBW) percentage of body composition consisting
of water, approximately 60% of body weight, less in obesity and more
in infants.
Intracellular fluid (ICF) volume that part of the TBW contained within the cells, approximately 40% of body weight and 2/3rds of TBW.
Muscle cells contain 75% water and fat cells have <5% water.
Extracellular fluid (ECF) volume that portion of the TBW outside the
cells, approximately 20% of body weight and 1/3rd of TBW, sustained
osmotically mainly by sodium.
Interstitial fluid volume that portion of the ECF outside the circulation and surrounding the cells.
23
Colloid a fluid consisting of microscopic particles (e.g. starch or protein) suspended in a crystalloid and used for intravascular volume
expansion (e.g. 6% hydroxyethyl starch, 4% succinylated gelatin, 20%
albumin, etc.).
Balanced crystalloid a crystalloid containing electrolytes in a concentration as close to plasma as possible (e.g. Ringers lactate, Hartmanns solution, Plasmalyte 148, Sterofundin, etc.).
Osmosis this describes the process by which water moves across a
semi-permeable membrane (permeable to water but not to the substances in solution) from a weaker to a stronger solution until the
concentration of solutes are equal on the two sides.
This force is termed osmotic pressure or, in the case of colloids e.g.
albumin, oncotic pressure. It is proportional to the number of atoms/
ions/molecules in solution and is expressed as mOsm/litre (osmolarity)
or mOsm/kg (osmolality) of solution. In clinical chemistry the term
osmolality is the one most often used. For example, out of approximately 280-290 mOsm/kg in extracellular fluid the largest single contributor is sodium chloride. This dissociates in solution and therefore
its component parts Na+ and Cl exert osmotic pressure independently
i.e. Na+ (140 mmol/kg), contributes 140 mOsm/kg, and Cl (100 mmol/
kg) contributes 100 mOsm/kg. Additional balancing negative charges
come from bicarbonate (HCO3) and other anions. In the intracellular
space K+ is the predominant cation (see below).
Because glucose does not dissociate in solution, each molecule,
although much larger than salt, behaves as a single entity in solution
and at a concentration of 5 mmol/kg, contributes only 5 mOsm/kg to
the total osmolality of plasma.
The cell membrane and the capillary membrane are both partially permeable membranes although not strictly semi permeable in the
chemical sense (see below). They act, however, as partial barriers
26
dividing the extracellular (ECF) from the intracellular fluid (ICF) space,
and the intravascular from the interstitial space. Osmotic or oncotic
shifts occur across these membranes, modified by physiological as
well as pathological mechanisms.
Anion gap the difference between the plasma concentration of the
major cation Na+ (135-145 mmol/l) and the major anions Cl (95-105
mmol/l) and HCO3 (22-30 mmol/l), giving a normal anion gap of 5-11
mmol/l.
It is enlarged in metabolic acidosis due to organic acids as in diabetic
ketoacidosis, lactic acidosis, renal failure, and ingested drugs and toxins.
Anion gap (mmol/l) = [Na+] ([Cl] + [HCO3])
The anion gap is normal in hyperchloraemic acidosis (e.g. after excess
0.9% saline administration). It is, therefore, useful in the differential
diagnosis of metabolic acidosis, although specific measurement of
organic acids such as -hydroxy butyrate or lactate may also be necessary to define the problem.
Strong ion difference (SID) Stewart has described a mathematical
approach to acid-base balance in which the strong ion difference
([Na+]+[K+]-[Cl]) in the body is the major determinant of the H+ ion
concentration. A decrease in the strong ion difference is associated
with a metabolic acidosis, and an increase with a metabolic alkalosis.
A change in the chloride concentration is the major anionic contributor to the change in H+ homoeostasis. Hyperchloraemia caused by a
saline infusion, therefore, will decrease the strong ion difference and
result in a metabolic acidosis.
Strong ion difference (mmol/l) = [Na+] + [K+] [Cl]
e.g. If Na+ is 140 mmol/l, K+ is 4 mmol/l and Cl is 100 mmol/l, the SID
is 44 mmol/l. The normal range is 38-46 mmol/l.
27
Base excess - Base excess is defined as the amount of strong acid that
must be added to each litre of fully oxygenated blood to return the pH
to 7.40 at a temperature of 37C and a pCO2 of 40 mmHg
(5.3 kPa). A base deficit (i.e., a negative base excess) can be correspondingly defined in terms of the amount of strong base that must
be added.
Acidaemia and Alkalaemia An increase in the H+ ion concentration
or a decrease in the pH is called acidaemia; a decrease in the H+ ion
concentration or an increase in the pH is called alkalaemia.
Acidosis and Alkalosis Processes that tend to raise or lower the H+
ion concentration are called acidosis and alkalosis respectively. These
may be respiratory, metabolic or a combination of both. CO2 retention
causing a rise in pCO2 in respiratory failure leads to respiratory acidosis and hyperventilation with a consequent lowering of pCO2 leads to
respiratory alkalosis. Accumulation of organic acids such as lactate or
-hydroxybutyrate or of mineral acidic ions such as chloride cause a
metabolic acidosis in which arterial pH falls below 7.4, bicarbonate is
reduced and pCO2 falls as the lungs attempt to compensate by blowing off more CO2. This is called a compensated metabolic acidosis.
Similarly, ingestion of alkalis such as bicarbonate or loss of gastric
acid cause a rise in pH and a metabolic alkalosis.
Maintenance - Provide daily physiological fluid and electrolyte
requirements.
Replacement - Provide maintenance requirements and add like for
like replacement for on going fluid and electrolyte losses (e.g. intestinal fistulae).
Resuscitation - Administration of fluid and electrolytes to restore
intravascular volume.
28
Significance
History
Autonomic
responses
Pallor and sweating, particularly when combined with tachycardia, hypotension and oliguria are suggestive of intravascular
volume deficit, but can also be caused by other complications,
e.g. pulmonary embolus or myocardial infarction.
Capillary refill
Blood pressure
Skin turgor
Sunken facies
Dry mouth
Oedema
Parameter
Significance
Urine output
Weighing
Fluid balance
charts
Serum
biochemistry
Urinary
biochemistry
30
History
This gives the initial clue to the likely abnormality and the type and
degree of deficit, e.g. a background of poorly controlled diabetes, a
story of vomiting and/or diarrhoea, diuretics in an elderly patient who
is confused, blood loss, burn injury etc.
Examination
Physical signs of fluid deficit are indicative but not specific, and no
conclusion should be drawn from any single feature (Table 4). The first
indication of a falling intravascular volume is a decrease in central
venous pressure (JVP/CVP). With progressive severity, pulse rate
increases (Fig. 5), followed by a fall in blood pressure with pallor and
sweating. The full-blown picture is called shock. In contrast, pink
warm peripheries, with rapid capillary refill after pressure, are usually
suggestive of an adequate circulation. Serial measurements of
JVP/CVP, pulse, blood pressure and urine output are sufficient to monitor most patients, but in complex cases or critical illness, such bedside examination may need to be supported by invasive techniques for
assessing cardiovascular function.
It should also be remembered that shock states due to volume depletion, cardiac causes, or sepsis share many similar features which
require expert assessment to distinguish.
31
Figure 5: Example of a vital signs chart showing a rising pulse rate and a falling
blood pressure, indicating progressive intravascular hypovolaemia secondary to haemorrhage.
the need for colloid to expand the intravascular volume, improve renal
blood flow and allow the excretion of the salt and water overload. If,
on the other hand, the jugular venous pressure (JVP) is elevated, then
immediate cessation of crystalloid administration, with or without
diuretics, will correct the underlying imbalance.
33
34
Laboratory tests
Haematocrit
Changes in fluid balance cause increase or decrease in the concentration of red cells, e.g. in the acute phase of burn injury, plasma loss
may be monitored by frequent haematocrit measurements, which
therefore help to guide fluid replacement. Loss of ECF due to gastroenteritis or other causes similarly increases haematocrit. Conversely
fluid overload causes a fall in haematocrit due to dilution.
Albumin
The albumin concentration behaves similarly to the haematocrit in
response to fluid deficit or excess. Indeed, dilution by infused crystalloids is one of the main causes of hypoalbuminaemia in surgical
patients. Another major cause is the increased albumin escape rate
from the circulation in response to proinflammatory cytokines
(Chapter 1).
Urea
With renal impairment due to either fluid deficit (pre-renal AKI) or
intrinsic AKI, blood urea concentration rises, the rate of increase being
greater in the presence of post injury catabolism. Urine output measurements are important but are subject to misinterpretation unless
other parameters are also considered. It is useful to combine measurement of urine volume with plasma and urine urea or osmolality
(mOsm/kg) to assess renal function. The urine to plasma urea ratio has
been used in the past to measure renal concentrating function and in
normal health can be as high as 100 in the presence of dehydration.
With a rising blood urea and creatinine, accompanied by oliguria,
urine to plasma urea ratio of <15 can be helpful in defining the transition to intrinsic from pre-renal AKI.
35
Osmolality
In the presence of AKI, a urine osmolality of >500 mOsm/kg is indicative
of a pre-renal cause (e.g. fluid deficit), whereas one <350 mOsm/kg
suggests that intrinsic renal damage has developed. Urinary and
serum osmolalities are also used in the diagnosis and monitoring of
diabetes insipidus and in the monitoring of hyper- and hypo-osmolar
states, to ensure that treatment is carefully controlled in order to
avoid too rapid changes in serum osmolality with consequent risks of
central nervous system damage.
Creatinine
Serum creatinine is a product of muscle metabolism and reflects muscle mass. Normally, therefore, it is higher in a 100 kg muscular man
than in a 40 kg elderly woman. For any individual, however, changes
in serum creatinine reflect renal function, although this has to fall by
more than 50% before the serum creatinine starts to rise. A more
sensitive measure of changes in renal function is creatinine clearance,
measured as: Creatinine clearance = (4 or 24 hr) urine creatinine concentration times urine volume divided by plasma creatinine concentration.
Sodium
This is expressed as a concentration, i.e. the proportion of sodium to
water in the ECF. It is not a measure of the absolute amount of sodium in the body or the need for a higher or lower intake. In fact, the
commonest cause of hyponatraemia is dilution by overenthusiastic
administration of hypotonic fluids. If, however, water balance is
known from daily weighing, then changes in plasma sodium can usually be interpreted in terms of sodium balance. For example, if weight
is unchanged, a fall in plasma sodium usually implies that sodium
balance is negative and that intake should be increased in the next
prescription. On the other hand, if weight has increased by 2 kg and
36
the plasma sodium has fallen, the balance of water is positive and
hyponatraemia is dilutional. The next prescription should include less
water and the same sodium intake as before.
An alternative approach to sodium balance is to measure intake and
the sodium content of all fluids lost. This however, is difficult to do
accurately as well as being more demanding in staff time and
resources.
A falsely low serum sodium may be caused by hypertriglyceridaemia,
since triglycerides expand the plasma volume but contain no sodium.
Similarly hyponatraemia occurs in the presence of hyperglycaemia as
in decompensated diabetes, since glucose also acts as an osmotic
agent holding water in the ECF. This effect disappears as soon insulin
treatment causes cellular uptake of glucose and lowering of its concentration in the blood.
Potassium
The normal serum potassium concentration lies between 3.5 and
5.3 mmol/l. Concentrations rising above 5.5 mmol/l progressively
increase the risk of death from cardiac arrest and require urgent
treatment which may include extra fluids, intravenous glucose and
insulin, bicarbonate, calcium gluconate (to stabilise the myocardium),
intrarectal calcium resonium and even renal replacement therapy.
Conversely, concentrations below 3.0 mmol/l increase the risk of
arrhythmias and indicate the need for potassium supplementation by
the oral or intravenous route.
37
Chloride
Despite the fact that serum chloride measurements do not increase
the cost of biochemical screening, many laboratories no longer report
serum Cl. However, in the differential diagnosis of acidosis, particularly in patients receiving 0.9% saline (with its high chloride content
in relation to plasma) intravenously, it may be an important parameter to detect the development of hyperchloraemic acidosis in which
the plasma chloride is elevated and bicarbonate reduced.
Bicarbonate
Venous or arterial bicarbonate concentrations indicate acid-base
status as described above.
Serial data charts
The sticking of individual reports in the back of notes makes it difficult to detect clinically important trends. The only satisfactory way of
monitoring patients with fluid and electrolyte problems is the use of
serial data charts on which, each day, important data are recorded, so
that changes and trends can be seen at a glance. Our own practice is
to record daily weight, serum biochemistry and haematology, etc., on
charts, which are kept by the patients bedside. Although transferring
data to such charts is time consuming, it reduces time taken in clinical decision making as well as improving the accuracy of prescribing.
It also compels one to look at reports and think carefully about their
significance.
38
Plasma/Blood
Haemoglobin (g/dl)
Haematocrit (%)
13.0-18.0 (men)
11.5-16.5 (women)
40-54 (men)
37-47 (women)
Na+ (mmol/l)
135-145
Cl
(mmol/l)
95-105
[Na+]:[Cl] ratio
1.28-1.45:1
K+
(mmol/l)
3.5-5.3
HCO3 (mmol/l)
22-30
Ca2+
2.2-2.6
Total
(mmol/l)
1.1-1.4
Mg2+
0.8-1.2
(mmol/l)
Glucose (mmol/l)
3.5-5.5
Urea (mmol/l)
2.5-6.7
Creatinine (mol/l)
60-120
pH
7.35-7.45
PaO2 (kPa)
11-13
PaCO2 (kPa)
4.7-5.9
Lactate (mmol/l)
0.6-1.8
Albumin (g/l)
33-55
Osmolality (mOsm/kg)
275-295
39
40
Change in
interstitial fluid
volume (ml)
5% albumin
1400-1500
400-500
25% albumin
250
-750*
6% hydroxyethyl
starch
1400-1500
400-500
Succinylated
gelatin
1400-1500
400-500
4000-5000
3000-4000
12000-14000
3000-4000
5% dextrose
Change in
intracellular fluid
volume (ml)
9000-10000
* Fluid is drawn into the intravascular compartment from the interstitial compartment
41
to salt and water overload, but who still have a plasma volume deficit,
as it helps draw fluid from the interstitial space into the intravascular
space and improves renal perfusion allowing excretion of excess salt
and water. Albumin is also used in patients with hepatic failure and
ascites. However, the prescription of this expensive preparation
should be confined to senior clinicians.
Although, in theory, colloids that are isooncotic with plasma should
expand the blood volume by the volume infused, in practice, the volume expanding capacity of these colloids is only 60-80%. Nevertheless, a given volume of colloid results in greater volume expansion
and less interstitial oedema than an equivalent volume of crystalloid.
Although, in practice in the UK, we use a combination of crystalloids
and colloids for resuscitation, there is, in fact, no firm evidence that
the use of colloids rather than crystalloids in the acute phase of injury
results in better outcome.
Table 7: Volume effects of some colloids
Colloidal solution
Duration of action
Initial plasma
expanding effect (%)
24-36 h
5-6 h
100
100
Medium acting
6% HES 200/0.5
10% HES 200/0.5
6% HES 130/0.40-0.42
4% Gelatin
3-4 h
3-4 h
4-6 h
3-4 h
100
140
100
90
Short acting
3% Gelatin
5% Albumin
2-3 h
2-4 h
70
70-90
Long acting
6% HES 450/0.7
6% HES 200/0.62
HES = hydroxyethyl starch. Properties are dependent on concentration, the weightaveraged mean molecular weight (Mw), the number-averaged molecular
weight (Mn), the molar substitution (MS) and the degree of substitution.
44
Disadvantages
Allergic reactions/anaphylaxis
[<0.4% - least for albumin (0.1%) and
hydroxyethyl starch (0.06%)]
Renal toxicity
Conclusion
There are good theoretical grounds for using colloids for plasma volume expansion as they cause less salt and water overload and oedema
than crystalloids. In practice, we tend to use a combination of the two
in varying proportion according to the circumstances. There are very
few indications for using 0.9% saline (e.g. chloride deficit from vomiting) and balanced crystalloids are preferred in most circumstances.
45
0.9%
Hartmanns
Lactated
Ringers
(USP)
Ringers
acetate
NaCl
Na+
(mmol/l)
135-145
154
131
130
130
Cl
(mmol/l)
95-105
154
111
109
112
1.28-1.45:1
1:1
1.18:1
1.19:1
1.16:1
3.5-5.3
24-32
29
(lactate)
28
(lactate)
27
(acetate)
Ca2+
(mmol/l)
2.2-2.6
1.4
Mg2+
(mmol/l)
0.8-1.2
3.5-5.5
pH
7.35-7.45
4.5-7.0
5.0-7.0
6-7.5
6-8
Osmolarity
(mOsm/l)
275-295
308
278
273
276
[Na+]:[Cl]
ratio
K+
(mmol/l)
HCO3 /
Bicarbonate
precursor
(mmol/l)
Glucose
(mmol/l)
46
PlasmaLyte 148
Sterofundin
ISO
0.18%
NaCl / 4%
dextrose
Plasma-Lyte
56
Maintenance
0.45%
saline
5%
dextrose
140
145
31
40
77
98
127
31
40
77
1.43:1
1.14:1
1:1
1:1
1:1
13
27
(acetate)
23
(gluconate)
24
(acetate)
5
(malate)
16
(acetate)
2.5
1.5
1.5
222.2
(40 g)
277.8
(50 g)
277.8
(50 g)
4.0-8.0
5.1-5.9
4.5
3.5-6.0
4.5-7.0
3.5-5.5
295
309
284
389
154
278
47
48
)
es ge
ss a
lo rrh
d,
w o
m
te
Ne ae
ita
sc es
.h
.g
su ss
(e
re lo
ly g
te oin
ua ng
eq o
Ad no
In
ad
eq
ua
te
Ad
re
eq
pl
u
bu at
ac
t o el
em
y
ng re
en
oi su
t
ng sc
lo ita
ss te
es d,
Resusciation
Adequate replacement,
no ongoing losses
Replacement
Maintenance
Inadequate maintenance/
ongoing losses
Intravenous
fluids
no longer
required
Oral
maintenance
Figure 6: The relationship between resuscitation, replacement and maintenance.
50
52
Table 10: Examples of maintenance fluid regimens (2-2.5 l/day) suitable for a 70 kg
person
0.18%
0.45% Plasmalyte
saline in saline maintenance
4%
(1-1.5 l)
dextrose
+ 5%
(2-2.5 l) dextrose
(2-2.5 l)
(1 l)
Ringers
lactate
(1 l) + 5%
dextrose
(1-1.5 l)
Hartmanns
(1 l) + 5%
dextrose
(1-1.5 l)
Sterofundin
ISO
(1 l) + 5%
dextrose
(1-1.5 l)
Water
(l)
2-2.5
2-2.5
2-2.5
2-2.5
2-2.5
2-2.5
Na+
(mmol)
60-75
77-116
80-100
130
131
145
Cl
(mmol)
60-75
77-116
80-100
109
111
127
Should
be
added
Should
be
added
26-33
50
100-125
K+
(mmol)
Dextrose
80-100
(g)
4
5
4
(Additional (Additional (Additional
K should
K should
K should
be added
be added
be added
to the 5% to the 5% to the 5%
dextrose)
dextrose)
dextrose)
50-75
50-75
50-75
Ca2+
(mmol)
2.5
Lactate
(mmol)
28
29
Acetate
(mmol)
32-40
Malate
(mmol)
Mg2+
(mmol)
24
5
3-4
53
54
Hypovolaemia
Clinical response
Yes
Continue IV fluids
guided by assessment
of volume status
No
Clinical response
Yes
No
55
56
57
58
Central
Modern single or multi lumen polyurethane or silastic cannulae
inserted via the internal jugular or subclavian vein have even greater
potential than peripheral cannulae to cause morbidity and mortality
unless inserted and maintained by skilled staff observing strict protocols.
Sub-cutaneous route (Hypodermoclysis)
This method has been used in paediatrics and geriatrics for many
years, but it is so effective for replacing small or medium fluid and
electrolyte losses in patients unable to maintain balance by the oral
route, that it deserves wider use. One of its virtues is that patients or
their carers can be taught to manage it at home. We have found it
particularly useful for domiciliary use in adult and elderly patients
with salt and water losses from gastrointestinal diseases.
0.9% saline (500-2000 ml daily) or 5% dextrose (500 ml) containing
up to 20 mmol K+ and/or 4 mmol Mg2+ per litre may be infused over
3-4 hours via a fine butterfly cannula inserted into the subcutaneous
fat, usually over the torso.
Infusion pumps
When fluid is delivered by either the enteral or parenteral route, what
is prescribed is not necessarily what is delivered and patients may
receive either too much or too little as a result of inaccuracies in
delivery rates. It is now recommended that fluids should be delivered
with infusion pumps at predetermined rates, which can be up to
999 ml/h. This increases the accuracy of fluid delivery. Nevertheless,
delays in changing fluid bags once they are empty may still lead to
inaccuracies.
59
Rate of infusion
41.7 ml/h
24 h
55.6 ml/h
18 h
83.3 ml/h
12 h
100 ml/h
10 h
125 ml/h
8h
166.7 ml/h
6h
250 ml/h
4h
500 ml/h
2h
999 ml/h
1h
Conclusion
In planning fluid replacement it is important to select the safest, simplest and most appropriate route and to monitor this carefully to
avoid over- or under-treatment and any potential complications of
the method. The aphorism, if the gut works, use it is as appropriate in
fluid therapy as it is in nutritional care.
60
7. Acid-Base Balance
Introduction
Maintenance within narrow limits of the normal acid base composition of the milieu interieur is essential for the optimal function of
tissues. The kidneys together with the lungs and liver play an essential
role in the maintenance of normal acid-base balance and arterial
blood pH (Table 12). The kidneys remove acid and regenerate bicarbonate, the lungs can regulate the removal of acid (CO2) by varying
respiratory rate and the liver removes and recycles lactate. Therefore,
patients with advanced chronic kidney disease (eGFR < 30 ml/min/
1.73 m2), liver disease or underlying respiratory disease are at
increased risk of developing acid-base abnormalities at times of acute
illness.
Table 12: Normal arterial blood acid-base measurements
pH
7.35 - 7.45
PaO2 (kPa)
10.7-16.0
PaCO2 (kPa)
4.7-6.0
HCO3 (mmol/l)
22 - 26
2 - +2
5 - 11
61
[ HCO3 ]
0.03 pCO2
haemoglobin
phosphate (organic and inorganic)
bone and its calcium salts
The kidney buffering system which
controls hydrogen (H+) and bicarbonate (HCO3) excretion or reabsorption as well as the conversion of ammonia (NH3) to ammonium
(NH4+) in the urine.
The lung buffering system which controls
the carbon dioxide (CO2) in the blood, increasing expired CO2 when
more is produced or to compensate for metabolic acidosis.
The liver buffering system which
removes and recycles the large amounts of lactate produced by
anaerobic respiration (the Cori cycle).
Disease states can disrupt this finely balanced system resulting in a
dangerously low (pH <7.1) or dangerously high pH (pH >7.6). Specific
patient management will depend upon the clinical status of the
patient and correction of the underlying cause. This chapter will pro62
63
65
Effect on pH
Metabolic acidosis
HCO3
Pco2
pH
Metabolic alkalosis
HCO3
Pco2
pH
Respiratory acidosis
Pco2
HCO3
pH
Respiratory alkalosis
Pco2
HCO3
pH
Ketoacidosis
diabetes
Lactic acidosis
tissue hypoxia
liver failure
metformin
Drug toxicity
ethylene glycol
methanol
salicylate
Kidney disease
chronic kidney disease
acute kidney injury
66
Table 15: Causes of metabolic acidosis (hyperchloraemic) with a normal anion gap
Fluid depletion
vomiting
gastric suction
diuretics
Hyperaldosteronism
Cushings syndrome
70
72
8. Oliguria
Introduction
Oliguria is defined as a urine output < 0.5 ml/kg/h. It may be physiological (a normal response to surgery/injury) or pathological (secondary to acute kidney injury (AKI). It is important to establish the
cause of AKI with the most common cause being hypovolaemia and/or
sepsis resulting in hypoperfusion of the kidneys (Chapter 9). There are
other causes of renal hypoperfusion (e.g. cardiac causes), but this
chapter will focus on that caused by hypovolaemia.
Physiological oliguria
Oliguria occurring soon after uncomplicated surgery is usually part of
the normal physiological response to injury, conserving salt and water
in an attempt to maintain intravascular volume. Isolated oliguria in
the first 48 hours after uncomplicated surgery does not necessarily
therefore reflect hypovolaemia, although it may do so if confirmatory
features of intravascular hypovolaemia are present, e.g. tachycardia,
hypotension, low central venous pressure (CVP/JVP), decreased capillary refill, etc. (Table 17).
The key clinical question is whether or not the oliguria is secondary to
significant intravascular hypovolaemia requiring treatment. It is,
therefore, essential that the patients volume status is assessed carefully (Table 17). Remember that serial changes give more information
than single observations. Also remember the importance of charting
data in a serial manner and in a way that is easily accessible to the
clinician. In difficult cases, particularly intra-operatively, invasive
monitoring may be required additionally to guide optimal treatment.
73
74
75
76
Diuretics
A common clinical question with oliguric AKI is whether the administration of loop diuretics (furosemide, bumetanide) improves renal
recovery by increasing urine output. Studies have demonstrated that
the use of high-dose loop diuretic to increase urine output in patients
with established AKI does not decrease the need for renal replacement therapy or improve survival.
Loop diuretics may have a short-term role in managing fluid overload
and pulmonary oedema. In these patients intravenous loop diuretics
may be used cautiously to try and establish a diuresis and treat the
pulmonary oedema. If the patient fails to respond, referral to the renal
team is recommended. It must be remembered that high-dose loop
diuretics are not without side-effects and may cause permanent hearing loss.
77
Hypovolaemia
Yes
No
IV fluids to correct
hypovolaemia
Exclude obstructed
urinary tract
Oliguria is fluid
responsive
Continue with
maintenance fluids
Yes
No
Continue with
maintenance fluids
Stop iv fluids
Consider iv loop diuretics if
fluid overloaded
Regular review of
volume status
Monitor electrolytes
Regular review of
volume status
Monitor electrolytes
Figure 9: Flow chart for the management of the oliguric surgical patient.
78
No
79
Definition
AKI is a result of a rapid fall in glomerular filtration rate occurring
over hours or days. The consequences include a failure to regulate
fluid and electrolyte balance and a failure to excrete metabolic waste
products and drugs.
AKI is defined when one of the following criteria is met;
Serum creatinine rises by 26 mol/l within 48 hours or
Serum creatinine rises 1.5 fold from a baseline value measured
within the previous week or
Urine output is < 0.5 ml/kg/h for > 6 consecutive hours
If serum creatinine concentration has not been measured in the previous week, use the most recent creatinine concentration measured
within the last three months. AKI can be staged according to the
criteria in Table 19.
Table 19: Stages of acute kidney injury
Stage Serum creatinine (SCr) criteria
80
Any patient who meets the criteria for AKI should have a thorough
clinical evaluation, which includes an assessment of volume status,
fluid balance and medication chart in order to identify any potential
causes for the AKI. In the majority of cases, AKI may be reversible if
the cause is identified and appropriate management implemented.
Aetiology of Acute Kidney Injury
If the criteria for diagnosing AKI have been satisfied, it is important to
identify its underlying aetiology as this will determine the most
appropriate therapy and influence whether early referral to nephrology is necessary. AKI can be considered as pre-renal, intrinsic and
post-renal (Fig. 10). Pre-renal and post-renal can both be considered
as functional processes that may progress to damage to the
parenchyma if not treated promptly.
Figure 10: Classification of AKI
ACUTE TUBULAR
INJURY
ISCHAEMIA / SEPSIS
INTERSTITIAL
NEPHRITIS
(10%)
ACUTE
GLOMERULONEPHRITIS
(5%)
TOXINS
81
Intrinsic AKI
Post-renal AKI
tubular injury
ischaemia/
reperfusion injury
nephrotoxins
aminoglycosides
cisplatin
intravenous
iodinated
contrast media
myoglobin
myeloma light
chains
blocked urinary
catheter
glomerular
glomerulonephritis
interstitial
interstitial nephritis
drugs
infections
vascular
atheroembolic
disease
cholesterol
embolisation
retro peritoneal
fibrosis
kidney stones
prostatic disease
pelvic tumour
renal vein
thrombosis
iatrogenic injury
to both ureters
Clinical Features
There should be a high index of suspicion for AKI, particularly in an
acutely ill patient with risk factors. Information about the patients
previous kidney function (e.g. serum creatinine), particularly over the
preceding 3 months, is a vital part of the evaluation. As in every other
clinical condition, diagnosis is achieved by weighing all the evidence
derived from a full history, examination and appropriate investigations. Serial changes in clinical features are often more revealing than
single measurements taken at any one time. AKI should be considered
as part of the differential diagnosis in patients presenting with the
following clinical features (Table 21).
Table 21: Clinical features of patients with suspected AKI and recommended baseline investigations
History
Examination
Investigations
general
weight
temperature
skin turgor (over
clavicle)
mucous membranes
(misleading if
mouth breathing)
skin rash (vasculitis)
joint swelling
(vasculitis)
uveitis (vasculitis)
symptoms
predisposing to
hypovolaemia
vomiting
diarrhoea
poor oral intake
blood/plasma loss
symptoms suspicious
of vasculitis
uveitis
skin rash
joint pains
haemoptysis
ultrasound of renal
tract within 24 hours
if obstruction
suspected
83
History
Examination
urinary symptoms
anuria
frequent dribbling
or passage of small
volumes of urine
suprapubic
discomfort
volume status
capillary refill
pulse rate
jugular venous
pressure
BP (lying and
standing)
heart sounds
(gallop rhythm)
lungs (pulmonary
oedema)
peripheral oedema
full medication
history including
over-the-counter
medications
herbal remedies
Investigations
abdomen
bladder distension
intra-abdominal
hypertension
rectal or pelvic
examination if
obstruction
suspected
84
Urinary electrolytes
The measurement of urinary electrolytes and osmolality can be used
to distinguish pre-renal AKI from intrinsic AKI (Table 22). The measurements of urinary sodium are not accurate if loop diuretics have
been administered within the previous 12 hours or there is pre-existing chronic kidney disease.
Parameter
Pre-renal
Intrinsic
<20
>40
>500
<350
Urine/plasma urea
>8
<3
>40
<20
<1
>2
85
Management
Prevention
Any patient admitted to hospital who is acutely ill or undergoing
major surgery who has been identified as at risk of developing AKI
(Table 18) should
Treatment
Once a patient has developed AKI, treatment is initially supportive but
ultimately dependent upon the underlying cause. Treatment involves
the following:
Identify and treat the underlying cause (not all AKI will be secondary to hypovolaemia and/or sepsis)
Volume status assessment
If hypovolaemic
consider insertion of a central venous pressure (CVP) line and
urinary catheter (not mandatory and could introduce infection) to aid with the assessment of volume status
resuscitate with IV fluids
stat 500 ml bolus (250 ml if cardiac failure) of a balanced
crystalloid (e.g. Hartmanns solution or Ringers lactate)
rapidly. If hyperkalaemia is present (K+ >5.5 mmol/l) or
suspected oliguric AKI or rhabdomyolysis 0.9% saline is
preferred initially (no potassium in crystalloid). However,
there is no evidence that administration of crystalloids
containing 3-5 mmol/l of K+ worsen the hyperkalaemia.
assess clinical response to fluid in terms of
capillary refill time
pulse (reduction in pulse if tachycardic)
jugular venous pressure (rise in JVP)
blood pressure (rise in BP)
pulmonary oedema
urine output (increasing if oliguric)
87
88
Immediate treatment
iv 10 ml 10% calcium gluconate over 2-5 minutes (cautiously, as extravasation can cause tissue damage). This stabilises
the myocardium rapidly, but has no effect on serum potassium concentration. Further doses may be required until
reduction in plasma potassium concentration is achieved.
Onset of action 2-4 minutes. Duration of action 30-60 minutes.
Further treatment
10 u fast acting insulin (actrapid) added to 50 ml of 50%
dextrose infused iv over 20 minutes to increase cellular
potassium uptake. Blood glucose must be monitored closely.
Onset of action 15-30 minutes. Duration of action 4-6
hours.
5 mg salbutamol nebuliser (up to a maximum of 10-15 mg
back to back) to stimulate cellular potassium uptake. Avoid
in patients on beta blockers and/or who have a history of
cardiac arrhythmias. Onset of action 30 minutes. Duration of
action 2-4 hours.
Medication review - stop any drugs that contain potassium
or interfere with renal excretion of potassium (ACE inhibitors, angiotensin receptor blockers, beta-blockers, potassium sparing diuretics)
Review potassium intake including intravenous fluids and
enteral or parenteral feeds
89
acidosis
pH 7.2-7.4 there is very little evidence to support correction with bicarbonate.
pH < 7.2 isotonic sodium bicarbonate 1.4% solution can be
used in stable patients not imminently requiring RRT. Bicarbonate therapy may worsen intracellular acidosis and deliver
excessive sodium load. In presence of hypocalcaemia bicarbonate can cause a further reduction in calcium and provoke
convulsions. Bicarbonate should only been used when calcium is known, and near normal, and following senior advice.
Renal replacement therapy will be required if the patient is
hypervolaemic and /or refractory to medical treatment
pulmonary oedema
sit the patient up and provide supplementary oxygen (up to
60%) via venturi face mask. A non-rebreathing (reservoir)
mask (15 l/min O2) may be required if severe pulmonary
oedema is present.
buccal glyceryl trinitrate 2-5 mg works rapidly and can be
repeated as frequently as required. If intolerable headache or
hypotension develops, this resolves rapidly after removing
the tablet from the mouth.
iv glyceryl trinitrate 50 mg in 50 ml 0.9% saline. Commence
at 2 ml/hr and titrate up to 20 ml/hr maintaining systolic
BP > 95 mmHg.
iv furosemide can be tried if the patient is haemodynamically stable and adequately intravascularly filled. The dose is
dependent on the severity of AKI. Furosemide 160 mg (slow
infusion over 1 hour) may be required for severe AKI
(stage 3) (Table 19).
renal replacement therapy if the patient is in extremis
being ventilated
90
uraemic encephalopathy
renal replacement therapy
uraemic pericarditis
renal replacement therapy
Medication management
In patients with AKI it is important to identify medications that are
normally metabolised and/or excreted by the kidneys, and either avoid
or make appropriate dose adjustments. Common examples include:
penicillins
cephalosporins
vancomycin
morphine (metabolites will accumulate)
low molecular weight heparin
If the patient is hypotensive there should be a low threshold for withholding antihypertensive therapy which will only exacerbate renal
hypoperfusion. Common examples include:
angiotensin-converting enzyme inhibitors
angiotensin receptor blockers
diuretics
Nephrotoxic medications should be avoided if possible (unless lifesaving) and include:
non-steroidal anti-inflammatory drugs (NSAIDs)
gentamicin
amphotericin
91
Referral to nephrologist
NOT all patients diagnosed with AKI need to be referred
Prior to referral the following should be performed
a thorough clinical history and examination (including fluid
balance/volume status assessment)
initial investigations (as recommended above)
initial supportive management (as recommended above)
Early renal referral is recommended in the following patients
AKI stage 3 (SCr 3 baseline value) (Table 19)
persistent oliguria and/or rising serum creatinine despite supportive therapy
complications refractory to medical treatment
Recovery
The first signs of recovery from oliguric AKI may be an increase in
urine output. Alternatively recovery may be heralded by a reduction in
the rise in the daily serum creatinine followed by a plateau in its value
prior to a fall. Recovery from AKI can result in a polyuric state in some
patients with the production of large urine volumes until the capacity
of the renal tubule to concentrate urine returns. There must therefore
be careful attention to the patients volume status and fluid requirements.
Patients can be at risk of developing a free water deficit which manifests as hypernatraemia and requires an increased intake of water
(intravenous 5% dextrose if unable to take water orally). Failure to
address the free water deficit promptly will not only slow renal recovery but will also put the patient at risk of neurological complications.
Another potential complication is the development of hypokalaemia,
which requires appropriate therapy due to the risk of cardiac arrythmias and ileus. A balanced crystalloid containing potassium is recommended in this clinical context. If further potassium is required consider infusing dextrose saline (4%/0.18%) with added potassium
93
Follow up
Acute kidney injury is a recognized antecedent for chronic kidney disease and patients require follow up.
The discharge summary to primary care should summarise:
the cause of AKI
risk factors for AKI
medications stopped and started
blood pressure (longer term monitoring required)
kidney function
Refer patients to nephrology left with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2.
94
95
96
Table 23: Features of DKA and HONK compared (approximate values only)
Parameters
Normal
range
Mild
DKA
Moderate
Severe
HONK
Blood glucose
mmol/l
3.5-11.1
(random)
> 14
>14
> 14
> 30
Arterial pH
7.35-7.45
7.2-7.3
7.0-7.2
<7.0
>7.3
HCO3 mmol/l
22-30
15-18
10-15
<10
Normal to
slightly
reduced
Urine ketones
Absent
++++
++++
++++
5-10
>10
>12
>12
Variable
280-295
280-320
280-320
280-320
>320
3-4
4-5
>5
6-10
Sodium (mmol)
200-280
280-350
> 350
350-700
Potassium (mmol)
200-280
280-350
> 350
> 350
Treatment
Aims
These are similar in both DKA and HONK, although with differences of
emphasis.
Restore the circulation and the ECF deficit by initially rapid fluid
infusion. This also has a beneficial metabolic effect reducing the
blood glucose, addresses circulatory failure and prerenal AKI,
reducing both acidosis and serum K+.
Seek the underlying cause of the diabetic decompensation (e.g.
sepsis) and treat it.
97
98
Monitoring
Monitor blood glucose, urinary ketones, acid-base status, serum
potassium, sodium, chloride and, if appropriate, osmolality, every
hour or two initially. Watch particularly for a fall in serum potassium and correct this with increased potassium input to maintain
serum K+ in the range of 3.3-4.5 mmol/l. Monitor clinical status,
vital signs, kidney function and urine output.
Fluid prescription
Traditionally, 0.9% saline has been used for resuscitation, followed by
0.45% saline with 5% dextrose and KCl as the volume deficit nears
restoration. Recent studies suggest that using a balanced electrolyte
solution avoids the hyperchloraemic acidosis associated with administration of 0.9% saline.
Hypotonic solutions pose a risk of too rapid a fall in osmolality unless
the plasma sodium and osmolality are monitored carefully and the
infusion rate controlled accordingly. It should be remembered that
glucose acts like Na+ as an ECF osmotic agent, so that as the blood
glucose falls with insulin treatment, water passes from the ECF to the
ICF, thereby concentrating the ECF sodium by 1.6 mmol/l for every
5.6 mmol/l fall in blood glucose. It is common, therefore, particularly
in HONK, to see the plasma Na+ rise with treatment necessitating a
switch to a more hypotonic solution. It is at this point that switching
from 0.9% to 0.45% saline may be useful gradually to reduce the
plasma Na+ to normal.
Although there is a phosphate deficit in decompensated diabetes, and
phosphate levels fall with treatment, phosphate supplementation has
not been shown to be beneficial.
99
100
101
102
With normal water balance and negative salt balance. This classically occurs in Addisons disease with its loss of both mineralocorticoid and glucocorticoid secretion and clinical features of weakness, weight loss, pigmentation and hypotension. Hyponatraemia
occurs not only due to renal salt loss, but also due to the kidneys
impaired ability to correct osmolality; firstly because salt loss
causes ECF hypovolaemia, which excites ADH secretion and secondly because hydrocortisone has a permissive role in the distal
tubule, allowing urinary dilution. In its absence, free water clearance is impaired, the basis for the old Kepler water load test for the
condition. Nowadays diagnosis is made simply by measuring serum
cortisol levels and their response to Synacthen.
With water excess and negative sodium balance. This occurs when
excess salt losses from the GI tract or the kidneys (diuretics or
tubular disease) are combined with excess water or hypotonic fluid
intake by mouth or other routes. The sodium depletion causes
hypovolaemia, which, in turn, stimulates not only the renin
angiotensin aldosterone system but also ADH secretion, thereby
impairing free water clearance and any osmolar correction.
In critical illness
In severe catabolic illness e.g. burns, septicaemia etc., cell membrane function may be impaired and the sodium pump affected so
that intracellular Na+ levels rise and those in the ECF fall despite
considerable positive Na+ balance. This has been called the sick
cell syndrome. With improved tissue perfusion and oxygenation
and correction of underlying sepsis this may resolve. In the past,
insulin, glucose and potassium have also been used with effect.
Hypernatraemia
The most common cause is net loss of hypotonic fluid from the GI
tract e.g. vomiting and diarrhoea, so that in relation to plasma, pro103
portionately more water is lost than sodium, even though sodium balance is also negative. The same occurs with renal losses due to the
osmotic diuresis associated with uncontrolled diabetes. Large fluid
losses from sweat, e.g. in the tropics, may also produce the same
effect. The rare primary hyperaldosteronism also causes mild hypernatraemia.
Treatment is with hypotonic fluids orally, enterally or intravenously
with frequent monitoring of serum biochemistry. Oral water may be
sufficient in mild cases. In the presence of diarrhoea oral rehydration
solutions may be appropriate. Severe cases should be treated cautiously with hypotonic intravenous fluids (e.g. 5% dextrose, 0.18%
saline in 4% dextrose) taking care to avoid too rapid reduction in
plasma sodium or osmolality. Correction should be achieved during
48 hours at a rate no greater than 2 mmol/l/h to avoid cerebral oedema.
Chloride (Cl)
This is the main anion of the ECF at a concentration of 95105 mmol/l. Unfortunately, because most clinical chemistry laboratories gave up reporting the serum chloride as part of routine screening,
abnormal states such as hyperchloraemic acidosis have sometimes
gone undetected. As a consequence, metabolic acidosis due to chloride has not infrequently been mistaken for other causes of acidosis
and inappropriate treatment given. We, therefore, advise that serum
chloride should always be measured in the presence of a metabolic
acidosis or whenever large volumes of saline have been administered.
It is important to remember that while the concentration of Na+ in
0.9% saline is 10% higher than that in plasma, the concentration of
Cl is 50% higher. This solution also has a pH of 5.5.
The main cause of hypochloraemic alkalosis is loss of gastric juice
(with its high HCl content) by vomiting or gastric aspiration. This is
the main indication for giving 0.9% saline.
104
Potassium (K+)
The total body K+ lies between 3000 and 3500 mmol and is contained
largely in the intracellular space at a concentration of 120145 mmol/l, where it is the chief cation, balancing the negative
charges on proteins and other non-diffusible anions. Only a very small
proportion is in the ECF, where its concentration lies crucially in the
narrow range 3.5-5.2 mmol/l. The balance of K+ across the cell membrane is maintained by the sodium pump combined with the GibbsDonnan equilibrium as described in Chapter 1. The normal daily
requirements are 1 mmol/kg body weight. The following points are of
clinical importance:
Hyperkalaemia: the serum K+ rises with renal failure and catabolic
states, e.g. the response to injury. During the flow phase of injury, as
glycogen and protein are broken down, K+ linked to them is released
from the cells into the ECF. Conversely, during the convalescent or
anabolic phase of injury, the cells take up K+ again as glycogen and
protein are resynthesised, causing a fall in ECF levels. Serum K+ levels
also rise in response to internal haemorrhage or tissue damage, e.g.
muscle necrosis, as K+ is released from dead cells. If acute kidney
injury (AKI) and a catabolic state are combined, serum K+ levels rise
rapidly to dangerous levels, usually accompanied by a metabolic acidosis.
A rise above 6.0 mmol/l risks cardiac arrest and necessitates urgent
treatment. With fluid depletion and pre-renal AKI, intravenous fluids
may be sufficient, but additional treatment includes bicarbonate as
well as insulin and glucose, both of which drive K+ back into the cells,
but only temporarily (4-6 hours). This is a useful emergency measure
which may need repeating. Calcium gluconate also helps to stabilize
the heart. If these measures fail or oliguria persists, then calcium
resonium rectally or renal replacement therapy should be carried out
without delay (Chapter 9).
105
Hypokalaemia: a fall in serum concentrations below 3.5 mmol/l nearly always reflects K+ deficiency and is usually accompanied by alkalosis because of the interchange of K+, Na+, and H+ in the distal tubule,
although, with renal tubular defects and laxative abuse, acidosis may
be present. Although the relationship between the degree of
hypokalaemia and the total K+ deficit is not a precise one, in general
it takes a loss of 200-400 mmol to reduce the serum K+ from 4.0 to
3.0 mmol/l and a further loss of the same amount to reduce serum K+
to 2.0 mmol/l.
Symptoms include muscle weakness and, in more severe cases, as
serum K+ falls below 2.5 mmol/l, paralysis and cardiac arrhythmias.
The most common causes of hypokalaemia are GI fluid loss and
diuretic therapy. It should also be remembered that patients with diabetic keto-acidosis may have a deficit in excess of 400 mmol even
though at presentation the serum K+ may be high due to acidosis and
pre- renal AKI from fluid loss. As the acidosis is corrected and insulin
is given, K+ moves rapidly back into the cells and serum K+ concentrations plunge to dangerous levels unless adequate K+ replacement is
given (Chapter 9). A similar phenomenon is seen with the refeeding
syndrome (Chapter 12).
Immediate treatment should be aimed at raising the serum K+ to a
safe level above 3.0 mmol/l rather than correcting the whole deficit,
which can then be done more slowly over the next few days. With
mild hypokalaemia (3-3.5 mmol/l), oral supplements at an initial dose
of 60-80 mmol/day should be tried, although many patients find oral
supplements difficult to tolerate. KCl is preferred to provide Cl to
correct any accompanying alkalosis. The more easily tolerated effervescent K+ preparations provide undesirable bicarbonate.
In the presence of alkalosis, the distal tubules continue to excrete K+
in exchange for H+ even in the face of a K+ deficit. In long-term
diuretic therapy, a K+ sparing diuretic or spironolactone should be
106
107
108
110
In mild cases of hypomagnesaemia, oral replacement may be sufficient, using magnesium oxide or glycerophosphate. However Mg2+
salts are not well absorbed, and in more severe cases it may be
necessary to give as much as 160 mmol of MgSO4 intravenously in
saline over 48 hours to restore normal concentrations. In patients
undergoing intravenous feeding for gastrointestinal failure, daily
requirements are 8-12 mmol. An alternative method of replacement, which we have found extremely effective in restoring and
maintaining Mg2+ levels, as well as replacing salt and water losses,
is to give MgSO4 in 0.9% saline subcutaneously (hypodermoclysis)
at a concentration of 6-12 mmol/l in up to 2 litres over 4-6 hours
every day. This is particularly useful in short bowel syndrome or
inflammatory bowel disease and can readily be administered at
home by patients or their carers.
Phosphate (PO42)
This is an important constituent of food, the normal intake being
800-1400 mg/day. Most is in the ICF, and the normal serum concentration lies between 0.89 and 1.44 mmol/l. Severe hypophosphataemia (< 0.32 mmol/l) such as may occur acutely in the refeeding
syndrome (Chapter 12) or chronically in diseases of bone and mineral
metabolism, risks symptoms of myopathy, dysphagia, ileus, respiratory
failure, impaired cardiac contractility and encephalopathy. Severe
cases may necessitate cautious intravenous administration of 300500 ml of Phosphate Polyfusor (Fresenius Kabi, 100 mmol PO42, 19
mmol K+ and 162 mmol Na+/l) or 30-50 mmol of PO42 in 1 litre 0.9%
saline over 6-12 hours with frequent monitoring of serum PO42 and
other electrolytes. Excessive or too rapid intravenous administration
risks precipitating acute hypocalcaemia and deposition of Ca2+ in soft
tissues. Less severe cases can be treated orally with 1 g/day phosphate
(e.g. Phosphate-Sandoz) replacement.
111
112
113
114
Thiamine deficiency
Alcoholic and severely malnourished patients are particularly liable to
this complication as they already have low thiamine reserves. Since
this is consumed as a cofactor in carbohydrate metabolism, refeeding
particularly with carbohydrate may precipitate symptoms of thiamine
deficiency including confusion, cerebellar signs with nystagmus, and
peripheral neuropathy. These are irreversible once established so that
identification of patients at risk and the giving of prophylactic treatment are vital. This latter may be achieved by giving 200 mg of thiamine intravenously at the start, followed by 300 mg daily by mouth
or 100 mg intravenously. Thiamine deficiency may also present as wet
beri-beri with heart failure.
Hypomagnesaemia, mild 0.5-0.7 mmol/l, severe < 0.4 mmol/l:
(normal range 0.7-1.0 mmol/l)
Magnesium, being involved in the formation of ATP is taken up by
cells during refeeding. Deficiency leads to muscle weakness, may
cause cardiac arrhythmias, and may cause hypocalcaemia by reducing
parathormone levels. It is not necessary in most cases to give prophylaxis except in those cases with prior Mg2+ deficiency such as those
with short bowel syndrome. Monitoring Mg2+ concentrations in
patients at risk and giving supplements if levels fall below 0.7 mmol/l
is usually sufficient. Daily requirements are 0.2 mmol/kg/d intravenously or 0.4 mmol/kg/d orally. If Mg2+ concentrations fall below
0.5 mmol/l then give 24 mmol MgSO4 iv over 24 hours.
115
116
Postoperative morbildity
Figure 11: The dose-response curve for fluid therapy showing the ill effects of
imbalance. (With permission from: Varadhan KK, Lobo DN. Perioperative
fluid management in enhanced recovery. In: Francis N, et al (eds) Manual of Fast Track Recovery for Colorectal Surgery. Springer, London, 2012)
Reduced circulating
blood volume
Increased
cardiopulmonary
complications
Decreased renal
perfusion
Altered coagulation
Microcirculatory
compromise
Hypoaemia
Release of reactive
oxygen species
Mitochondrial
dysfunction
Endothelial
dysfunction
Multiple organ
failure
Fluid deficit
Normovolaemia
Hyperchloraemic acidosis
Pulmonary oedema and
decreased gas exchange
Splanchnic oedema
Raised intra-abdominal
pressure
Decreased mesenteric and
renal blood flow
Decreased tissue oxygenation
Intramucosal acidosis
Ileus
Impaired wound healing
Anastomotic dehiscence
Decreased mobility
Altered coagulation
Microcirculatory compromise
Reactive oxygen species
Mitochondrial dysfunction
Endothelial dysfunction
Multiple organ failure
Fluid overload
117
position to postoperative parotitis, and an increase in viscosity of pulmonary mucus resulting in mucous plug formation and ateletactasis.
Induction of anaesthesia in patients with a fluid deficit further
reduces the effective circulatory volume by decreasing sympathetic
tone. Inadequate fluid resuscitation and decreased tissue perfusion
can lead to gastrointestinal mucosal acidosis and poorer outcome.
A recent meta-analysis of patients undergoing major abdominal surgery has shown that patients managed in a state of fluid and electrolyte balance had a 59% reduction in risk of developing complications when compared with patients managed in a state of fluid
imbalance (deficit or excess). There was also a 3.4 day reduction in
hospital stay in the fluid balance group. Moreover, maximum weight
gain was seen in the studies in which the standard group received an
excessive amount of fluid. It appears that patients need to gain at
least 2.5-3 kg in weight, as a result of salt and water overload, in the
postoperative period in order to have a worse outcome than those
maintained in a state of zero fluid balance. Avoidance of fluid overload, rather than fluid restriction seems to be the key to better postoperative outcome.
Moore and Shires wrote in 1967, The objective of care is restoration
to normal physiology and normal function of organs, with a normal
blood volume, functional body water and electrolytes. This can never
be achieved by inundation. This recommendation has never been bettered.
120
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128
Index
0.9% saline
abdominal
acetate
46, 53
acute phase
albumin
anaphylactic shock
anatomy
arterial
blood flow
blood glucose
capillary membrane
10, 11, 20
21, 24, 26, 42
57, 113, 114, 115
cardiac arrest
111, 119
cardiac failure
51, 55, 75
79, 82, 86, 87
62
cardiac output
119
82
cardiovascular
31, 114
7, 9
cell membrane
9, 10, 26
103, 105, 110
19, 51, 76
blood viscosity
119
10, 24, 25, 29
41, 42, 44, 74
117, 120
7, 9, 10, 52
cerebral oedema
36
blood pressure
body fluid
101, 113
carbohydrate
blood loss
blood volume
brain damage
central venous
bleeding
bowel
ammonia
body weight
34
31, 73
75, 87
98, 101, 104
chloride
circulation
citrate
coagulation
coagulopathy
57
43, 45, 51, 117
119
129
colloids
compensatory
continuous monitoring
creatinine
creatinine concentrations
17
crystalloid administration
32, 33
daily maintenance
86
dehydration
dextrans
43
dextrose
diuresis
fasting
118
fluid administration
fluid balance
fluid depletion
fluid infusion
30, 97, 98
fluid replacement
fluid resuscitation
fluid spaces
9, 10
fluid therapy
43, 51
diuretics
drugs
encephalopathy
endothelial dysfunction
energy
gas exchange
gastrointestinal
70
15
13
49, 119
gelatin
glucose
117
evaporation
117, 118
3, 11, 12, 13, 14, 42
49, 51, 52, 54, 59
67, 68, 108, 110, 111
119, 120
gastrointestinal function
epidural analgesia
130
extravascular
52, 118
daily weights
electrolytes
76
crystalloids
extracellular fluid
glycogen
haematocrit
Hartmanns solution
hypoalbuminaemia
29, 35, 65
109, 123
41
headache
90,119
heart
heart failure
heart sounds
hypokalaemia
hypokalaemic
74, 84
heparin
91
hepatic
44
66, 67
hydrocortisone
103
hydrogen
62, 63
hydrostatic pressure
11
hydroxybutyrate
hydroxyethyl starch
hypodermoclysis
69, 104
hyperchloraemia
18
hyponatraemia
hypoparathyroidism
hypoperfusion
109
30, 73, 75, 82, 91
hypothalamus
hypotonic fluid
16
20, 36, 102, 103, 104
hypotonic saline
42
hypovolaemia
hypovolaemic
26, 43, 45
hyperaldosteronism
59, 111
21, 30, 87, 93, 96
106, 107, 113, 114
27, 30, 42
hyperchloraemic acidosis
27, 38, 42
99, 104, 117
118, 119
immunoglobulin
43
indications
infants
inflammation
19, 58
hyperglycaemia
inflammatory
hyperkalaemia
hyperkalaemic
hypernatraemia
hyperparathyroidism
hypertension
hypertriglyceridaemia
hyperventilation
hypervolaemia
insulin
75, 87
30, 93, 101
103, 104
108, 109
79, 84
37
28, 70, 119
74, 102
23
insulin infusion
98, 100
insulin resistance
insulin secretion
95
95, 96, 107, 113
insulin treatment
intracellular component
intracellular fluid
intracellular protein
37, 96, 99
10
9, 23, 27, 41
21
131
morbidity
intravascular space
mortality
muscular
intravascular volume
myocardial infarction
29
myocardium
37, 88
non-steroidal
86, 91
invasive monitoring
34, 73
invasive techniques
31, 34
iodinated contrast
84, 86
irritability
isotonic
42, 86, 89
normovolaemia
117
oedema
oncotic pressure
laboratory tests
29, 35
lactate
osmolality
osmoreceptors
92
osmotic effect
17
83
osmotic sensors
16
lithium
liver function tests
lymphatics
11, 20
108, 113, 114, 118
mechanical ventilation
metabolic acidosis
70
metabolic alkalosis
metabolic water
metabolism
microcirculatory compromise
117
microvascular perfusion
119
132
oxygenated blood
oxygenation
paediatrics
pathophysiology
perfusion
13, 14
6, 16, 36, 64, 68
95, 111, 115
16
oxygen saturations
oxygen species
malnutrition
76, 88
117
28
103, 117, 118
59
5, 19, 22
perioperative fluid
physiology
5, 7, 9, 13, 18, 19
22, 120
plasma proteins
11, 24
plasma sodium
plasma urea
plasma volume
renal tubules
respiratory acidosis
28, 66, 69
respiratory alkalosis
respiratory disease
61, 70
respiratory failure
polyurethane
respiratory process
59
polyuria
109
positive charges
21, 24
post-operatively
post-renal
81, 82
postoperative bleeding
19, 76
postoperative morbildity
postoperative period
pre-renal
preoperative fluid
pruritus
45
pulmonary oedema
pulse rate
rehydration solutions
renal function
renal perfusion
57, 104
27, 79, 105
119, 120
resuscitation
Ringers lactate
risk factors
saline infusion
sepsis
septic shock
shock
67, 82
19, 31, 55, 64, 67, 82
98, 122, 123, 127
sodium balance
sodium bicarbonate
sodium chloride
sodium concentration
sodium depletion
30, 103
sodium pump
9, 103, 105
sodium retention
sodium transport
119
starch
61, 76, 88
restriction
118
protein catabolism
renal failure
118, 120
pre-renal AKI
pressure
117
respiratory rate
65
Starling effect
26, 41, 43
44, 45, 57
11
133
Stewart approach
63, 71
sympathetic tone
120
systolic
29, 90
tachycardia
33, 73, 74
tachypnoea
33
temperature
28, 29, 83
tissue damage
88, 105
tissue hypoxia
66
tissue oedema
42
tissue perfusion
total blood volume
total body sodium
total body water
transcapillary escape
trauma
vasodilatation
82
vasopressin
16
venous catheters
34
venous pressure
volume deficit
volume of colloid
44
volume of crystalloid
volume replacement
43, 76
volume status
water balance
5, 13, 14, 30
34, 36, 54, 74
101, 102, 103
101
9, 10, 17, 23, 41
11, 20, 21
21, 79, 102, 118
weight
134
42, 44
135
Dileep N. Lobo
Andrew J. P. Lewington Simon P. Allison
Basic Concepts
of Fluid and
Electrolyte Therapy