ARTICLE IN PRESS

Current Paediatrics (2003) 13, 520 --528

c 2003 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.cupe.2003.08.008

Understanding and managing acute fluid and

electrolyte disturbances
Birgit Bockenkamp* and H.Vyasw
*
Paediatric Intensive Care Unit Fellow, Queen’s University Medical Centre, Nottingham, UK
w
Consultant in Intensive Care and Respiratory Medicine, C/O Paediatric Intensive Care Unit, University Hospital, Queens Medical Centre,
Nottingham, NG72UH, UK

KEYWORDS Summary Fluid and electrolyte balance is important in infants and young children
hypovolaemia; dehydration; because of their high total body water content and basal metabolic rate. Excessive fluid
electrolytes; losses lead to dehydration and hypovolaemia.Inadequate and delayed treatment lead to
hypernatraemia; progressive deterioration in tissue perfusion, vascular collapse and progressive multiple
hyponatraemia; organ failure. However, hasty rehydration may be just as devastating as dehydration in
hyperkalaemia; seriously ill paediatric patients with severe electrolyte imbalance. Rapid correction of
hypokalaemia; sodium imbalance can produce cerebral oedema or osmotic demyelination. As a rule,
hypophosphataemia; sodium correction of 1--2 mmol/l/h is recommended; rates higher than that may lead
hyperphosphataemia to death.Hyperkalaemia is an emergency that requires prompt correction medically or
with dialysis. Hypocalcaemia, hypokalaemia and hypophosphataemia are increasingly
recognized as critical, especially in septic patients.Fluid and electrolyte disorders should
be approached by considering the def|cit, the maintenance fluid and continuing losses,
and a rate of replacement which will not produce severe neurological def|cit.

c 2003 Published by Elsevier Ltd. All rights reserved.

* Tumour lysis syndrome will produce hyperphos-

PRACTICE POINTS
* Hypovolaemia refers to any state in which the ex-
tracellular fluid volume is reduced
* Hypernatraemia due to water loss is dehydration
* The plasma sodium concentration is maintained
within a very narrow range by changes in water in-
take, thirst and changes in ADH secretion
* Hyponatraemia arises due to volume depletion re-
placed with hypotonic fluid
* SIADH is a very important clinical cause of hypo-
natraemia
* Hyper- and hyponatraemia both present with neu-
rological signs and symptoms
* Rapid correction of sodium levels may produce
cerebral oedema or osmotic demyelination
* Hyperkalaemia can be effectively treated by nebu-
lized b-2-adrenergic agonists, insulin and glucose
* Hypocalcaemia and hypophosphataemia in sepsis
should be corrected aggressively
Correspondence to: HV. E-mail: harish.vyas@mail.qmcuh-tr.trent.nhs.
uk
phataemia which may respond to saline infusion
or dialysis
Fluid and electrolyte balance play a vital role in
maintaining homeostasis, helping to regulate and
maintain cellular function, control tissue perfusion and
maintain acid--base balance. In normal healthy indivi-
duals, intake and output are maintained at a steady
state, and the main role of the kidneys is the regulation
of water balance in the body. Osmoregulation is almost
completely mediated by osmoreceptors in the hypotha-
lamus, influencing both thirst and the secretion of
antidiuretic hormone (ADH). Under normal circum-
stances, the sensitive hypothalamic osmoreceptors
detect any change in extracellular tonicity, and respond
by altering secretion of ADH. However, when a child
becomes ill, the ability to regulate this f|ne balance is
perturbed, leading to either fluid retention or excessive
fluid loss. The resulting hypo-osmolality or hyperos-
molality may produce serious neurological conse-
quences due to rapid shifts of water into and out of the
brain.
 ARTICLE IN PRESS
ACUTE FLUID AND ELECTROLYTE DISTURBANCES
In this review, we will examine some of the most com-
mon fluid and electrolyte disturbances seen in the criti-
cally ill patient.
WATER BALANCE
Eighty percent of neonatal body weight is comprised of
water, with the proportion dropping to between 50 and
60% in adult women and men, respectively. Sixty percent
of body water is intracellular, and the rest is
extracellular. Water is required to replace losses from
urine, sweat, faeces and moist surfaces of the skin and
respiratory tract. Maintenance requirements are not di-
rectly proportional to weight, but to energy expendi-
ture per unit mass. Obligatory urine loss occurs due to
the need to remove various solutes from the body. The
minimum water required for urine is dependent on the
daily solute excretory load and the maximum urinary
concentration achievable. In infants, decreased concen-
trating and diluting capacity of the kidneys can lead to
abnormal water balance, and may explain the rapidity
with which infants dehydrate. The ability maximally to
concentrate urine is achieved between 3 and 6 months
of age.
ESTIMATIONOF DEFICIT
Hypovolaemia and dehydration
Hypovolaemia refers to a state in which the extracellular
fluid (ECF) volume contracts. In very severe cases, this
can lead to poor peripheral tissue perfusion. It can be
caused by salt and water loss alone, as in severe diar-
rhoea, vomiting and bleeding, or by water loss alone, as
in dehydration. Salt and water are primarily lost from
ECF. Pure water is lost from total body water, of which
only 40% is extracellular. It is for this reason that nearly
2.5 times as much fluid needs to be lost to result in the
same degree of ECF depletion as in salt and water loss.
Patients with water loss and dehydration will always be
hypernatraemic, whereas those with salt and water loss
will have a normal or even a reduced plasma sodium con-
centration.
Causes of volume depletion
The most common cause of acute severe volume loss is
gastroenteritis, with diarrhoea and vomiting. In very sick
children, gastric haemorrhage and surgery can cause vo-
lume losses that may not be recognized early, leading to
catastrophic consequences. Excessive renal losses may
occur from osmotic diuresis, e.g. diabetes mellitus, poly-
uria due to diabetes insipidus and salt-wasting nephropa-
thies. Iatrogenic volume depletion may be caused by
inappropriate use of diuretics. Skin losses due to exces-
521
sive sweating, high fever or high ambient environmental
temperature are a major concern, especially in hot
weather.The current fashion of extreme activity and ec-
stasy (3- 4 methylenedioxymethamphetamine, ‘MDMA’)
ingestion in teenagers may lead to a potentially fatal out-
come. Burns, hyperventilation and third-space losses
(e.g. multitrauma with crush injury, multiple fractures,
intestinal obstruction) cause severe hypovolaemia that
is often diff|cult to treat.
Conditions associated with reduced water
requirement
This is a relatively uncommon situation, most often ob-
served in hypothermic patients and those with extreme
inactivity, such as coma or vegetative states. Infants and
children nursed in very high humidity may not require a
high fluid intake. Patients with renal failure associated
with oliguria or anuria may have their fluids restricted,
as will those with severe fluid retention due to cardiac
failure.
Clinical presentation
The history obtained from the parents will indicate the
duration and severity of unusually large fluid losses. Iden-
tif|cation of source of fluid loss, such as diarrhoea, as well
as documentation of fluid intake will help in clinical man-
agement. Although evaluation of water def|cit is usually
clinical, elevated serum creatinine and blood urea con-
centrations may indicate dehydration. Otherwise,
laboratory investigations are most useful in the assess-
ment of co-existing electrolyte abnormalities. Physical
examination can be misleading in the assessment of dehy-
dration of overweight and malnourished infants. Tachy-
cardia may be the only sign of dehydration in obese
infants, whilst dehydration is often overestimated in se-
verely emaciated infants. Neurological signs may be the
only clinical abnormalities present in hypernatraemic
dehydration, with skin and circulatory changes being
misleadingly absent.
Symptoms of volume depletion
The presenting symptoms will depend on the degree of
dehydration, the type of predominant fluid loss and the
associated electrolyte disturbances.
Volume depletion
(see Table 1)
The symptoms are due to reduced tissue perfusion. Se-
vere hypovolaemia will lead to ischaemia of the gut and
cerebral tissue. In addition, reduced blood flow asso-
ciated with hyperviscosity may lead to thrombotic
events, acidosis and multiple organ dysfunction. Delayed
 ARTICLE IN PRESS
522
Table 1 Signs and symptoms of hypovolaemia
Mild Moderate
Thirst Very thirsty
Mild oliguria Oliguric
Minimal physical Tachycardia
signs
Mild weight loss Sunken eyes/ infants with sunken
o5% fontanelle
5--10% weight loss
or inadequate resuscitation will lead to severe irreversi-
ble acidosis and death.
Type of fluid lost
When pure water loss predominates, for instance dia-
betes mellitus, the patient will demonstrate symptomatic
hypernatraemia rapidly. The symptoms are weakness, ir-
ritability and excessive tiredness, leading to seizures and
coma if untreated.
Allied symptoms
Depending upon the losses, associated electrolyte and
metabolic disturbances such as acidosis and hyperglycae-
mia may be present. Hypokalaemia is usually present,
although deterioration in renal function may produce
dangerous hyperkalaemia. Cardiovascular effects of hy-
pokalaemia include arrhythmias and hypotension in se-
vere cases. Marked muscle weakness will be present in
both hypo- and hyperkalaemia. Hypomagnesaemia is
commonly associated with hypokalaemia, further ex-
acerbating muscle weakness.
SODIUM IMBALANCE
Hypernatraemia
The kidneys are the main organ maintaining salt home-
ostasis, adjusting urine concentration to match salt in-
take and loss. Hypernatraemia due to a loss of free
water is rare in healthy children; any rise in plasma toni-
city stimulates ADH and increases thirst.The increase in
water intake returns the plasma sodium concentration
to normal levels. This mechanism maintains the sodium
level within a very narrow range, despite a very variable
intake of salt and water. However, in the very young and
children with developmental delay, thirst is often poorly
recognized by carers and may result in hypernatraemia.
It is def|ned as a serum sodium concentration exceeding
145 mmol/l.
CURRENT PAEDIATRICS
Severe
Too obtunded to drink
Severe oliguria or anuria
Marked, tachycardia, hyperpyrexia,
cyanosis
Loss of skin tone, sunken eyes
Abdominal pain, apathy, restless, fatigue,
delirium or comatose
Small heart size on chest X-ray
When hypernatraemia occurs, cells become dehy-
drated due to water moving extracellularly across the
osmotic gradient, as well as contributing to the total
body water loss. The shrinkage of brain cells, if severe
enough, will produce venous rupture and subarachnoid
haemorrhage. To prevent this contraction, cells respond
by moving electrolytes across the cell membrane, result-
ing in the alteration of the resting potential across the
cell membrane. Later, intracellularly generated organic
solutes help maintain cell volume and prevent damage.
Rapid correction of hypernatraemia will permit water
to move across this osmotic gradient into the cells, pro-
ducing cerebral oedema.
Major causes of hypernatraemia
Hypovolaemic hypernatraemia
This occurs when water loss is greater than sodium def|-
cit. Normally, a large quantity of fluid is produced by the
gastrointestinal tract; however, only a small quantity is
lost in the stools. Huge quantities of fluid may be lost if
the amount of fluid re-absorbed is impaired, as in vomit-
ing, losses from f|stula and secretory diarrhoea. Under
normal circumstances, more than 98 --99% of water f|l-
tered across the glomerular membrane is re-absorbed.
Osmotic diuresis from mannitol, high urea and diuretics
will reduce re-absorption. Following relief of renal ob-
struction, massive diuresis can occur and result in severe
volume depletion. Water lost by evaporation from the
skin and respiratory tract can become substantial in a
hot, dry climate, febrile states and if thirst is impaired.
When the barrier property of skin is breached by burns
or exudative skin lesions, water loss is substantial. Pul-
monary losses can occur from losses into the pleural
space. Decreased thirst, either behavioural or secondary
to damage to the hypothalamic thirst centres, can lead to
dehydration. Any impairment in either ADH secretion
or excessive loss of dilute urine in nephrogenic diabetes
insipidus can lead to a comatose state.
Hypervolaemic hypernatraemia
This is present when sodium gain is greater than water
gain. It is caused iatrogenically when hypertonic saline
solutions are used to maintain sodium levels over
 ARTICLE IN PRESS
ACUTE FLUID AND ELECTROLYTE DISTURBANCES
170 mmol/l in the management of signif|cantly raised in-
tracranial pressure in traumatic head injury. Accidental
or non-accidental sodium poisoning in infants and young
children has been reported. Excessive sodium bicarbo-
nate administration and mineralocorticosteroid excess
(Cushing’s syndrome) can also lead to this state.
Euvolaemic hypernatraemia
This reflects water losses accompanied by inadequate
water intake. It is commonly seen when the renal collect-
ing duct fails to respond to ADH, e.g. in advanced renal
disease, hypokalaemia, hypercalcaemia, Fanconi syn-
drome and sickle cell disease. It also may be seen in cen-
tral diabetes insipidus, head injury, during and following
encephalitis, meningitis or Guillain-Barre! syndrome,
especially if thirst is severely impaired. It is occasionally
seen in the very young due to compulsive water drinking.
Hyponatraemia
Hyponatraemia is def|ned as serum sodium of less than
135 mmol/l and results from retention of excess water.
When there is excessive loss of free water, the associated
rise in the plasma sodium concentration produces thirst
to correct the abnormality. Dilution of plasma sup-
presses ADH, allowing dilute urine to be excreted. An
inability to suppress ADH release results in hyponatrae-
mia. More than one mechanism may play a part in produ-
cing hyponatraemia.
Major causes of hyponatraemia
The most common cause of hyponatraemia is ADH re-
lease following circulatory collapse. In severe diarrhoea,
replacement of sodium losses with relatively low-so-
dium-containing solution will produce hyponatraemia.
This may also arise in extreme athletes if they replace salt
and water losses with water only. In cirrhosis and conges-
tive heart failure, although the plasma volume may be
markedly increased, the fall in cardiac output and loss of
peripheral vascular tone will increase ADH levels. In ne-
phrotic syndrome, hyponatraemia is of renal origin. Thia-
zide diuretics, as opposed to loop diuretics, may produce
marked hyponatraemia. Hyponatraemia can occur in pa-
tients with adrenal insuff|ciency and with hypothyroid-
ism. In advanced renal failure, osmotic diuresis is
produced by increased solute excretion. Dietary causes
include poor nutrition and excessive water intake. Ec-
stasy ingestion associated with excessive water intake
and inappropriate ADH secretion may produce fatal
hyponatraemia.
There are two other disorders associated with hypo-
natraemia which are syndrome of inappropriate ADH
secretion (SIADH) and cerebral salt wasting (CSW).
These should be considered in any sick patient with hy-
ponatraemia. The diagnostic features are hypo-osmolal-
ity, a urine sodium concentration that is usually above
40 mmol/l and a urine osmolality above 100 mosmol/kg.
523
The acid--base balance and potassium may be normal
and low plasma uric acid is usually present. The most
common causes of SIADH are listed inTable 2.Treatment
involves water restriction, although, in severe cases, salt
administration with a loop diuretic may be necessary. In
CSW, intracranial disorders such as haemorrhage, trau-
ma, tumours and infection produce hyponatraemia in a
setting of volume depletion and natriuresis. Inappropri-
ate atrial natriuretic peptide (ANP) secretion has been
postulated as a possible mechanism for CSW. ANP has
been shown to inhibit both renin and angiotensin-II-
mediated aldosterone secretion. It is vital to differentiate
it from SIADH, since the wrong diagnosis and manage-
ment may be fatal. Aggressive replacement of urinary
salt and water losses using normal saline or 3% saline, if
necessary, is the mainstay of treatment of CSW. Minera-
locorticoids are not always effective.
Neurological symptoms of hypernatraemia and hypo-
natraemia are shown inTable 3.
Diagnosis and management of sodium
imbalance
Investigations: As a rule, repeat the test if the results are
abnormal to check its validity
Hypernatraemia
It is vital to check paired plasma and urine electrolytes
and osmolality. Blood and urinary glucose will identify
diabetes mellitus and ensure that an osmotic diuresis
has not taken place. Hypernatraemia is almost always as-
sociated with high urine osmolarity and reduced urine
output, and concentrated urine indicates hypotonic fluid
losses. High urine osmolarity is observed in salt overload
states; however, the urine output may continue to re-
main high. Diuretic administration and CSW will pro-
Table 2 Causes of syndrome of inappropriate anti-
diuretic hormone secretion
* Central nervous system
--Trauma
--Intracranial bleeding
--Meningitis
--Intracranial tumours
* Pulmonary
--Infection, either bacterial or viral (e.g. bronchiolitis)
--Asthma
--Pneumothorax
* Post-abdominal or--thoracic surgery
* Drugs.Chemotherapeutic drugs, e.g.
cyclophosphamide and vincristine,Hormonal
treatment, e.g. desmopressin and vasopressin
 ARTICLE IN PRESS
524
Table 3 Symptoms of hypernatraemia and hyponatrae-
mia (the predominant symptoms of sodium imbalance are
neurological)
Hypernatraemia Hyponatraemia
* Lethargy * Apathy, nausea and malaise
* Weakness * Weakness
* Irritability * Lethargy
* Convulsion * Headaches
* Twitching * Convulsions and obtundation
* Coma * Hyper-reflexia
duce isotonic urine osmolality. Hypotonic urine, polyuria
and serum sodium levels of over 170 mmol/l will conf|rm
diabetes insipidus. Water deprivation is only performed
once the patient has normal sodium and osmolarity. It is
a complex test which needs to be carried out with great
care and detail.Neuro-imaging is suggested in all patients
with severe hypernatraemia to rule out any central
cause.
Hyponatraemia
Rule out factitious factors producing hyponatraemia
such as high proteins, hypertriglyceridaemia and high
blood sugar.Urinary sodium levels will depend on the un-
derlying cause of hyponatraemia (see Table 4). Cortisol
levels and thyroid function tests need to be performed,
and neuro-imaging may be necessary for initial diagnosis
as well as for prognostication.
Management
Resuscitation
In the presence of circulatory failure, infusion of fluids is
essential to prevent tissue dysfunction and organ failure.
The current practice is to use normal saline, 20 ml/kg, as
a rapid infusion; greater volumes are administered if tis-
sue perfusion remains poor. Ventilatory support may be
required if there is a poor response and larger volumes
are required. As a rule, ventilate patients when replace-
ment fluid during initial resuscitation is over 50% of circu-
lating volume.
General rules on rate ofcorrection of sodium
* Rapid correction is potentially dangerous in both hy-
pernatraemia and hyponatraemia.
* Mortality in patients with sodium levels exceeding
160 mmol/l is very high.This may be due to the under-
lying cause, but can be aggravated by rapid correction
of hypernatraemia.
CURRENT PAEDIATRICS
Table 4 Urinary sodium losses in hyponatraemia
Urinary sodium Urinary sodium 420
o20 mmol/l mmol/l
Diarrhoea Diuretics including osmotic
diuresis
Excess sweating Water intoxication
Third space Salt-wasting nephropathy
losses
Congestive Proximal renal tubular
heart failure acidosis
Nephrotic Adrenal insuff|ciency, e.g.
syndrome Addisonian crisis
Cirrhosis Syndrome of
inappropriate ADH
secretion
Hypothyroidism
Acute or chronic renal
failure (440 mmol/l)
* Speedy onset of hyponatraemia with sodium concen-
trations below 120 mmol/l generally results in more
severe symptoms and poorer outcome.
* A rate of correction of1--2 mmol/l/h is recommended.
Higher rates may lead to fatal cerebral oedema or an
osmotic demyelination syndrome.The presentation of
this syndrome may be delayed for a few days and may
be irreversible and even lead to death.
POTASSIUM IMBALANCE
Potassium is the most abundant intracellular cation and
is necessary for maintaining the normal charge differ-
ence between intra- and extracellular compartments.
Ninety-eight percent of total body potassium is found
within cells at a concentration of 150 mmol/l, a situation
that is maintained by membrane-bound Na+-K+-ATPase.
Potassium transport towards the intracellular space may
be decreased during hypoxia and induced hypoglycaemia.
Acidosis decreases the renal excretion of potassium and
potentiating arrhythmogenicity of hyperkalaemia.
Ninety percent of potassium is excreted in urine, with
stool and sweat losses contributing the rest. Almost all
the f|ltered potassium in the kidney is re-absorbed pas-
sively in the proximal tubule and loop of Henle. Most ur-
inary potassium is derived from potassium secretion in
the distal nephron in the cortical collecting tubule. This
process is primarily influenced by aldosterone which pro-
motes sodium absorption and promotes potassium ex-
cretion. When hypokalaemia is present, the kidney
lowers potassium excretion by decreasing the secretion
and increasing the active potassium re-absorption via
H+-K+-ATPase pumps in the luminal membrane of the
cortical collecting tubule.
 ARTICLE IN PRESS
ACUTE FLUID AND ELECTROLYTE DISTURBANCES
Hypokalaemia
Hypokalaemia is caused by losses from gastrointestinal
and urinary tracts or due to increased translocation into
cells. Diarrhoea is the most common cause of hypokalae-
mia in children worldwide. Loss of secretions from the
lower gastrointestinal tract is usually associated with bi-
carbonate loss and acidosis; however, decreased potas-
sium intake and hypovolaemia-induced hyperaldostero-
nism will increase urinary potassium excretion leading
to hypokalaemia.The urinary potassium wasting seen in
this setting is only present for a few days. Subsequently,
the bicarbonate re-absorptive capacity increases sub-
stantially, thus reducing urinary sodium and potassium
losses.Vomiting and loss of gastric acid leads to alkalosis
with increased urinary potassium secretion. Laxative
abuse is an uncommon but important cause of hypoka-
laemia in children.
Diuretics increase distal delivery of potassium, leading
to increased urinary losses. Volume depletion activates
the renin--angiotensin--aldosterone system, thus increas-
ing urinary potassium losses. Mineralocorticoid excess,
e.g. Cushing’s syndrome, is characterized by urinary po-
tassium wasting. These patients are often hypertensive
and may be on diuretics which would further exacerbate
hypokalaemia.Renal disease with elevated secretion of re-
nin leads to hyperaldosteronism. In many clinical settings
(high-dose penicillin, glue sniff|ng), large quantities of so-
dium are re-absorbed in exchange for potassium, leading
to high potassium loss, a condition worsened by volume
depletion. In metabolic acidosis (e.g. diabetic ketoacidosis),
hypovolaemia-induced hyperaldosteronism and excessive
non-reabsorbable anions lead to potassium losses. The
process is often countered by potassium leakage out of
cells due to acidosis. Hypomagnesaemia leads to hypoka-
laemia. Hypokalaemia is produced by amphotericin ad-
ministration, polyuria and salt-losing nephropathies.
Increased potassium translocation into cell is pro-
duced by alkalosis, increased insulin and elevated b-adre-
nergic activity. Other causes include an increase in blood
cell production, hyperthermia, and drugs such as theo-
phylline and in chloroquine toxicity. Table 5 shows a com-
plete list of other causes of hypokalaemia.
Investigations
Clinical evaluation should include blood pressure and
12-lead electrocardiogram (ECG). Serum and urinary
electrolytes, osmolality, and glucose and renal function
tests are a prerequisite. Blood gas analysis and magne-
sium are essential if a metabolic condition is suspected.
Renin, cortisone and 17-ketosteroids should be per-
formed if endocrine dysfunction is suspected. Drug
screening may be appropriate in persistent hypokalaemia.
Signs and symptoms
(seeTable 6)
525
Assessment and monitoring
Monitoring of vital signs, including continuous cardiac
monitoring, is essential in all hypokalaemic patients. Re-
spiratory rate and pattern should be monitored and early
respiratory support may be necessary if hypoventilation
is present. Meticulous fluid balance is indispensable.
Management
Treatment depends on the severity and aetiology.
Asymptomatic hypokalaemia, e.g. due to gastroenteritis,
usually resolves spontaneously. In other patients, emer-
gency treatment needs to be initiated even before per-
forming an ECG. A variety of oral and intravenous
potassium preparations are available, and potassium
chloride is the most commonly used. This raises the ser-
um potassium concentration more rapidly than potas-
sium bicarbonate, and can also correct an underlying
chloride depletion that is often observed in metabolic al-
kalosis. Potassium phosphate could be of benef|t in the
treatment of diabetic ketoacidosis (DKA) and severe hy-
pophosphataemia seen in severe sepsis. Potassium bicar-
bonate is the preferred salt in renal tubular acidosis.
Enteral replacement is preferable if feasible, except in
life-threatening abnormalities such as ventricular ar-
rhythmias, digitalis intoxication or paralysis. It is impor-
tant to note that the total def|cit might be signif|cantly
higher than expected from the measured serum potas-
sium concentration (e.g. DKA). It is crucial to correct as-
sociated fluid and electrolyte disorders; for instance, if
hypomagnesaemia is not recognized and treated, hypo-
kalaemia will remain refractory to replacement therapy.
Also, correction of acid--base disorders will alter the ser-
um potassium concentration.
Hyperkalaemia
The origin is often multifactorial although renal failure,
drugs and acidosis are among the main causes in hospita-
lized patients. Hyperkalaemia is a life-threatening medi-
cal emergency. The main mechanism of hyperkalaemia is
increased potassium release from cells. In metabolic
acidosis, potassium exits cells to maintain electroneu-
trality, and in addition, there is impairment of the potas-
sium-reducing effects of insulin and b-adrenergic
agonists. Insulin def|ciency and hyperglycaemia prevent
potassium movement into cells. Hyperosmolality, for ex-
ample in uncontrolled diabetes mellitus and administra-
tion of mannitol, will produce osmotic water movement
out of the cells followed by passive potassium movement
through potassium channels and via solvent drag through
water pores. Increased tissue breakdown (e.g. large mus-
cle mass injury, cytotoxic drugs, radiation therapy) will
produce marked potassium release, often producing
life-threatening arrhythmias. b-Adrenergic blockers in-
terfere with b2-adrenergic facilitation of potassium up-
take. Succinylcholine in patients with burns, extensive
 ARTICLE IN PRESS

526 CURRENT PAEDIATRICS

Table 5 Major causes of hypokalaemia and hyperkalae- Table 6 Signs and symptoms of hypokalaemia and hy-
mia perkalaemia
Hypokalaemia Hyperkalaemia Hypokalaemia Hyperkalaemia
Gastrointestinallosses Potassium release from
cells * Numbness of * Drowsiness
extremities
* Diarrhoea and vomiting * Metabolic acidosis
* Decreased bowel * Decreased cardiac output
* Surgical drains * Insulin def|ciency sounds

* Hyperglycaemia * Ileus * Apathy, confusion

Urinary losses Catabolic states * Nausea and vomiting * Bradycardia

* Diuretics * Large muscle mass * Flabby muscles * Depression of STsegment

injury
* Paraesthesia * Prolonged PR interval
* Steroids * Cytotoxic drugs
* Digoxin toxicity * Flattening and widening of
* Hypomagnesaemia * Tumour lysis the P wave
syndrome
* STsegment depression * Tall, peaked, tented
* Drugs, e.g. amphotericin B T waves

* Salt-losing nephropathies * Flattened T waves * Abdominal cramping,

and polyuria nausea and diarrhoea

Other causes Other causes * U waves * Muscle flaccidity

* Plasmapheresis * Acute or chronic

renal disease are best avoided in hyperkalaemic states. It is important
to rule out factitious hyperkalaemia due to lysis of cells,
* Elevated -adrenergic * Acidosis e.g. leucocytosis and hereditary spherocytosis or throm-
activity, e.g. b-agonist bocytosis.Table 5 lists other causes.
therapy

* Sodium depletion
* Low cardiac output
states
* b-blockers
* Factitious in
leukaemia with very
high count
trauma or neuromuscular disease produces potentially
lethal hyperkalaemia. Reduced urinary potassium excre-
tion is a major cause of hyperkalaemia. In the oliguric
state, a high potassium diet, increased tissue breakdown
and hypoaldosteronism combine to produce severe
hyperkalaemia. Hypoaldosteronism, congenital adrenal
hyperplasia, Addison’s disease and low cardiac output
states can all reduce potassium excretion.Certain drugs,
such as potassium-sparing diuretics and ACE inhibitors,
Signs and symptoms
(seeTable 6)
Investigations
Serum electrolytes, urea and creatinine, glucose,
blood gas analysis and ECG are essential, although
ECG is not a sensitive method for detection of hyper-
kalaemia.
Management
Treatment depends upon the cause and severity. In mild
cases, it might be suff|cient to enhance excretion,
whereas in severe cases, administration of intravenous
calcium is urgently required. It is generally agreed, that a
plasma potassium concentration above 7.0 mmol/l, se-
vere muscle weakness or marked ECG changes are po-
tentially life threatening, and immediate treatment
should be initiated.
Treatment consists ofthree major components
Stabilization of electrically excitable membranes
Calcium directly antagonizes the membrane effects of
hyperkalaemia. Although 10% calcium chloride contains
 ARTICLE IN PRESS
ACUTE FLUID AND ELECTROLYTE DISTURBANCES
about three times more elemental calcium than an equal
volume of calcium 10% gluconate, it is more damaging to
tissue if extravasated. It is therefore important to infuse
it through a central vein. The onset of effect of both
preparations is rapid (within 1--3 min) and lasts for up to
1h. A continuous infusion may be required.
Shift from the extracellular to the intracellular compartment
* Insulin increases the activity of the Na+-K+-ATPase
pump, facilitating potassium transport into the cell.
The dose-related effect begins within 15 min and
peaks at 30 -- 60 min, lasting for 4 -- 6 h.
* Sodium bicarbonate raises the systemic pH, and the
resulting hydrogen ion release from the cells will be
exchanged for potassium. It works synergistically
with insulin and glucose.The effect begins within 30 --
60 min and lasts for several hours.
* In children with renal failure, nebulized salbutamol is
effective in lowering hyperkalaemia, although there is
a possibility of a secondary rise of the serum potas-
sium concentration after an initial response.
Removal from body
* Diuretics such as frusemide will produce kaluresis;
however, in the presence of oliguria, it may not be ef-
fective.
* The cation exchange resin binds potassium and re-
leases sodium in the gastrointestinal tract. It can be
given orally or as an enema. Due to its slow onset,
variable eff|cacy and rare but serious toxicity, the ca-
tion exchange resin with sorbitol is not the f|rst choice
for severe hyperkalaemia.
* Dialysis or haemof|ltration are the most eff|cient
ways of treating refractory and symptomatic hyper-
kalaemia.
CALCIUM IMBALANCE
Calcium homeostasis in the body is maintained by close
interaction between parathyroid hormone (PTH) and vi-
tamin D.
Hypocalcaemia
The mechanisms that produce hypocalcaemia are de-
creased PTH or low vitamin D. In neonates, the main
causes are birth asphyxia, low-birthweight pre-term ba-
bies and those delivered to diabetic mothers.Conditions
such as DiGeorge’s syndrome will have typical facies,
congenital cardiac anomaly and immunodef|ciency hypo-
calcaemia.The majority of cases will have microdeletions
involving chromosome 22. Late hypocalcaemia may be
found in certain mitochondrial cytopathies.
In older children, the causes include autosomal hypo-
parathyroidism and auto-immune type. Hypoparathyr-
oidism is an increasingly recognized complication
of sepsis. Hypocalcaemia associated with vitamin D de-
527
f|ciency is observed in dark skinned populations due to
reduced sun exposure. Malabsorption, as in coeliac dis-
ease and cystic f|brosis, produces vitamin D def|ciency.
Hypocalcaemia, hypoparathyroidism, and bone disease
occur in patients with end-stage renal disease. Resistance
to PTH in hypomagnesaemia leads to hypocalcaemia.
Signs and symptoms
Jitteriness and convulsions are observed in the newborn.
There may be numbness and tingling of f|ngers and lips.
Stiffness of joints and clumsiness may be noted early. Mus-
cle spasms, cramps, tetany and myalgia are very disabling
and painful. Laryngeal spasm is rare and frightening. Hy-
peractive reflexes, Trousseau’s sign and prolonged QT in-
terval are noted. Steatorrhoea can be a cause of, as well
as an effect of, hypocalcaemia. Symptoms reflect not only
the degree of hypocalcaemia, but also the acuteness of
the fall in serum calcium concentration. Children with
chronic hypocalcaemia may show few symptoms.
Treatment
The treatment of hypocalcaemia depends on the
underlying cause and varies with its severity. Intravenous
calcium alone may only be useful in conditions such
as sepsis, and may be transiently effective. The calcium
solution should be diluted, not mixed with phosphate
or bicarbonate, and administered into a large central
vein. In mild asymptomatic hypocalcaemia, diet alone
may be suff|cient or vitamin D may be required. Oral
phosphate binder to lower serum phosphate concentra-
tions is the treatment of choice in renal failure. In chil-
dren with renal failure, calcium can be added to the
dialysis fluid.
Hypercalcaemia
This is a rare situation in paediatrics. Conditions such as
hypervitaminosis D or excessive intake of calcium are in-
frequently observed. Malignancy induced hypercalcaemia
is rarely seen. The symptoms include lethargy, nausea,
polyuria, confusion, paraesthesias and coma. Shortening
of the QT interval is seen on ECG. Management requires
treatment of the underlying cause. Normal saline infu-
sion may be necessary to reduce levels by dilution.
PHOSPHATE IMBALANCE
Hypophosphataemia
In sick patients with sepsis, hypophosphataemia is com-
mon and is due to intracellular shift following inotropic
use. It occurs in DKA, following severe burns and due
to diuretic use. Decreased serum phosphates are
observed in patients with malnutrition, vomiting and
 ARTICLE IN PRESS
528
diarrhoea.Oral antacids in a sick patient may precipitate
hypophosphataemia.
Signs and symptoms
In an acute severe state, it produces confusion, seizures
and may lead to coma. Numbness and tingling of f|ngers
and lips are seen in mild cases. Decreased muscle
strength is common, and myocardial dysfunction is well
recognized in sepsis.
Treatment
Phosphate supplementation, either orally or intrave-
nously, may be necessary. Rapid infusion may precipitate
tetany due to a rapid drop in calcium.
Hyperphosphataemia
The kidneys are highly eff|cient at maintaining phosphate
balance; any increase in phosphate levels reduces proxi-
mal tubular phosphate re-absorption, and PTH also pos-
sibly contributes to this.
There are three general conditions in which this
occurs:
* Renal failure will initially diminish phosphate f|ltration
and excretion, with PTH helping to decrease proxi-
mal re-absorption. However, with further deteriora-
tion in renal function, phosphate intake will exceed
the kidneys, ability to excrete phosphate.
* Massive acute phosphate load, e.g. tumour lysis fol-
lowing chemotherapy, rhabdomyolysis, lactic and
ketoacidosis, and hypervitaminosis D.
* Hypoparathyroidism with reduced PTH secretion or
renal resistance to PTH results in increased phos-
phate re-absorption.
Signs and symptoms
Tachycardia may be an early sign, followed by muscle
weakness, hyper-reflexia and tetany. Anorexia, nausea
and vomiting are not unusual.
CURRENT PAEDIATRICS
Treatment
In severe acute hyperphosphataemia, as seen following
tumour lysis, phosphate excretion can be increased by
saline infusion; however, dialysis may be indicated if other
electrolyte abnormalities are present. In chronic hyper-
phosphataemia, treatment includes phosphate binders
and reduced phosphate in the diet.
FURTHER READING
1. Adrogue HJ, Madias NE. Hypernatraemia. N Engl J Med 2000; 342:
1493--1499.
2. Agarwal R, Afzalpukar R, Fordtran JS. Pathophysiology of potassium
absorption and secretion by the human intestine. Gastroenterology
1994; 107: 548--571.
3. Ayus JC, Varon J, Arieff AI. Hyponatraemia, cerebral edema, and
noncardiogenic pulmonary edema in marathon runners. Ann Intern
Med 2000; 132: 711--714.
4. Gennari FJ. Hypokalaemia. N Engl J Med 1998; 339: 451--458.
5. Holland PC, Thompson D, Hancock S, Hodge D. Calciphylaxis,
proteases, and purpura: an alternative hypothesis for the severe
shock, rash, and hypocalcaemia associated with meningococcal
septicemia. Crit Care Med 2002; 30: 2757--2761.
6. Lee JH, Arcinue E, Ross BD. Brief report: Organic osmolytes in
the brain of an infant with hypernatraemia. N Engl J Med 1994; 331:
439--442.
7. Mange K, Matsuura D, Cizman B et al. Language guiding therapy:
the case of dehydration versus volume depletion. Ann Intern Med
1997; 127: 848--853.
8. McClure RJ, Prasad VK, Brocklebank JT. Treatment of hyperka-
laemia using intravenous and nebulised salbutamol. Arch Child Dis
1994; 70: 126--128.
9. McManus ML, Churchwell KB, Strange K. Mechanisms of disease:
regulation of cell volume regulation in health and disease. N Engl J
Med 1995; 333: 1260--1266.
10. Sakarcan A, Quigley R. Hyperphosphataemia in tumor lysis
syndrome: the role of hemodialysis and continuous veno-venous
hemofiltration. Pediatr Nephrol 1994; 8: 351--353.
11. Vega RM, Avner JR. A prospective study of the usefulness of
clinical and laboratory parameters for predicting percentage
of dehydration in children. Pediatr Emerg Care 1997; 13:
179--182.
12. Wiederkehr MR, Moe OW. Factitious hyperkalaemia Am J Kidney
Dis 2000; 36: 1049--1053.