Disorders of Water Metabolism in Children: Hyponatremia and Hypernatremia Objectives

Disorders of Water Metabolism in Children: Hyponatremia and Hypernatremia Objectives

Article
fluids & electrolytes
Disorders of Water
Metabolism in Children:
Hyponatremia and Hypernatremia
Michael L. Moritz, MD,*
Juan Carlos Ayus, MD†
Objectives
After completing this article, readers should be able to:
1. Describe the clinical manifestations of hyponatremic encephalopathy.
2. Identify the risk factors for developing hyponatremic encephalopathy.
3. List the risk factors for developing cerebral demyelination following the correction of
hyponatremia.
4. Characterize the clinical manifestations of hypernatremia.
5. Identify patients at greatest risk for developing hypernatremia.
Introduction
In conjunction with the tremendous medical advances of the past century, an increasing
number of hospitalized patients are dependent on parenteral fluids. Caring for children
who have complex medical conditions has resulted in new challenges for prescribing
parenteral therapy to maintain sodium and water homeostasis; most electrolyte disturbances occur in the hospital. Although the kidneys play an important role in the development of disorders in water handling, most of the morbidity and mortality results from
central nervous system dysfunction (Table 1). This review discusses common disorders of
water metabolism, emphasizing the neurologic sequelae.
Hyponatremia
Hyponatremia is defined as a serum sodium level less than 135 mEq/L (135 mmol/L). It
is one of the most common electrolyte disorders encountered in hospitals, occurring in
approximately 3% of hospitalized children. The cause usually is identified easily, and the
condition rarely is fatal, but sometimes the cause can be elusive and mortality can result
from inappropriate therapy.
Pathogenesis
Under normal circumstances, the human body can maintain plasma sodium levels within
the normal range (135 to 145 mEq/L [135 to 145 mmol/L]), despite wide fluctuations
in fluid intake. The body’s primary defense against developing hyponatremia is the kidney’s
ability to generate dilute urine and excrete free water. The primary reasons that children
develop hyponatremia encompass underlying conditions that impair the kidney’s ability to
excrete free water (Table 2). Hyponatremia usually occurs in the setting of excess water
intake, with or without sodium losses, in the presence of impaired free water excretion.
Only under the most extreme circumstances can excess water intake or sodium loss alone
lead to hyponatremia in the absence of impaired free water excretion.
It is important to realize that the serum sodium concentration does not reflect total
body sodium content accurately. Rather, a decrease in serum sodium more closely reflects
an increase in total body water, and an increase in serum sodium reflects a free water deficit.
Diagnostic Approach
Before embarking on an aggressive therapeutic regimen, it is vital to confirm that
hyponatremia is associated with hypo-osmolality. Hyponatremia can be associated with
either a normal or an elevated serum osmolality (Fig. 1). The most common causes are
hyperglycemia, severe hyperproteinemia, or hyperlipidemia. Hyperglycemia results in
*Assistant Professor of Pediatric Nephrology, Children’s Hospital of Pittsburgh, Pittsburgh, PA.
†
Professor of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Pediatrics in Review Vol.23 No.11 November 2002 371
fluids & electrolytes hyponatremia & hypernatremia
Abnormalities of
Water Metabolism Leading to
Brain Damage
Table 1.
Hyponatremia
●
Syndrome of inappropriate secretion of antidiuretic
hormone
● Postoperative
● Oral water intoxication
● Diuretics
Hypernatremia
●
●
●
●
Gastroenteritis
Fluid restriction
Diabetes insipidus
Sodium excess
hyperosmolality, with a translocation of fluid from the
intracellular space to the extracellular space, resulting in a
1.6-mEq/L (1.6-mmol/L) decrease in levels of serum
sodium for every 100 mg/dL (5.6 mmol/L) elevation in
serum glucose concentration above normal. Severe hyperlipidemia and hyperproteinemia can cause a displacement of plasma water, which will result in a decreased
sodium concentration (pseudohyponatremia) with a
normal serum osmolality. Serum sodium levels currently
are measured by either direct- or indirect-reading ion-
Disorders of Impaired
Renal Water Excretion
Table 2.
Effective Circulating Volume Depletion
●
●
●
Gastrointestinal losses: vomiting, diarrhea
Skin losses: cystic fibrosis
Renal losses: salt-wasting nephropathy, diuretics,
cerebral salt wasting, hypoaldosteronism
● Edematous states: heart failure, cirrhosis, nephrosis,
hypoalbuminemia
Thiazide Diuretics
Renal Failure
●
●
Acute
Chronic
Nonhypovolemic States of Antidiuretic Hormone Excess
●
Syndrome of inappropriate secretion of antidiuretic
hormone
● Cortisol deficiency
● Hypothyroidism
372 Pediatrics in Review Vol.23 No.11 November 2002
selective electrode potentiometry. The direct method
will not indicate pseudohyponatremia because it measures the activity of sodium in the aqueous phase of
serum only. The indirect method may indicate
pseudohyponatremia because the specimen is diluted
with a reagent prior to measurement. The indirect
method is performed in approximately 60% of chemistry
laboratories in the United States; therefore, pseudohyponatremia remains an entity of which clinicians must be
aware. If hyponatremia is associated with hypoosmolality (true hyponatremia), the next step is to measure the urinary osmolality to determine if there is an
impaired ability to excrete free water (urineOsm
⬎100mOsm/kg).
The most useful information for correctly diagnosing
hyponatremia is a detailed history of fluid balance,
weight changes, medications (especially diuretics), and
underlying medical illnesses. Hyponatremia usually is a
multifactorial disorder, and a detailed history can identify
sources of salt and water losses, free water ingestion, and
underlying illnesses that prompt a nonosmotic stimulus
for vasopressin production. Assessment of the volume
status on physical examination and the urinary electrolytes on laboratory evaluation can be extremely helpful,
but both findings can be misleading. For patients in
whom hyponatremia is due to salt losses, such as from
diuretics, signs of volume depletion may be absent on
physical examination because the volume deficit may be
nearly corrected by oral intake of hypotonic fluids if the
thirst mechanism is intact.
In general, a urinary sodium concentration less than
25 mEq/L (25 mmol/L) is consistent with effective
circulating volume depletion, and a concentration
greater than 25 mEq/L (25 mmol/L) is consistent with
renal tubular dysfunction, use of diuretics, or the syndrome of inappropriate antidiuretic hormone secretion
(SIADH) (Fig. 1). Numerous factors can affect the urine
sodium, making interpretation difficult. Therefore, the
timing of the urinary measurements in relation to dosages of diuretics, intravenous fluid boluses, or fluid and
sodium restriction is important.
Clinical Manifestations
A major consequence of hyponatremia is influx of water
into the intracellular space, resulting in cellular swelling
that can lead to cerebral edema and encephalopathy. The
clinical manifestations of hyponatremia are primarily
neurologic and related to cerebral edema caused by
hypo-osmolality (Table 3). The symptoms of hyponatremic encephalopathy vary substantially among individuals; the only consistent symptoms are headache, nausea,
fluids & electrolytes hyponatremia & hypernatremia
Figure 1. Diagnostic approach to hyponatremia.
vomiting, emesis, and weakness. As the cerebral edema
worsens, patients develop behavioral changes and an
impaired response to verbal and tactile stimuli. Advanced
symptoms include signs of cerebral herniation, such as
seizures, respiratory arrest, dilated pupils, and decorticate
posturing. Not all patients have the usual progression in
symptoms; advanced symptoms can develop suddenly.
Children are at particularly high risk for developing
symptomatic hyponatremia. They develop hyponatremic
encephalopathy at higher serum sodium concentrations
than do adults and have a poor prognosis if timely
therapy is not initiated. This appears to
be due to the higher brain-to-skull size
ratio in children, which leaves less
room for brain expansion (Fig. 2).
Children’s brains reach adult dimensions by 6 years of age, but the full skull
size is not reached until 16 years of age.
Also, animal data suggest that prepubertal children have an impaired ability
to regulate brain cell volume due to
diminished cellular sodium extrusion
related to lower testosterone levels.
Hypoxemia is another major risk
factor for developing hyponatremic encephalopathy. The occurrence of a hypoxic event, such as respiratory insufficiency, is a major factor militating
against survival without permanent
brain damage in patients who have hyponatremia. The combination of systemic hypoxemia and hyponatremia is
more deleterious than is either factor
alone because hypoxemia impairs the
ability of the brain to adapt to hyponatremia, leading to a vicious cycle of
worsening hyponatremic encephalopathy (Fig. 3). Hyponatremia leads to
decreased cerebral blood flow and arterial oxygen content. Patients who have
symptomatic hyponatremia can develop hypoxemia by at least two different mechanisms: noncardiogenic pulmonary edema or hypercapnic
respiratory failure. Respiratory failure
can occur suddenly in patients who
have symptomatic hyponatremia. Most
of the neurologic morbidity reported
for children who have hyponatremia
has occurred in patients who have had a
respiratory arrest as a feature of hyponatremic encephalopathy.
Of the many conditions that have been associated
with hyponatremia, only a few are likely to lead to
symptomatic hyponatremia.
SIADH
SIADH is one of the most common causes of hyponatremia in the hospital and frequently leads to severe hyponatremia (plasma sodium, ⬍120 mEq/L [120 mmol/
L]). It is caused by elevated ADH secretion in the
absence of an osmotic or hypovolemic stimulus. SIADH
Pediatrics in Review Vol.23 No.11 November 2002 373
fluids & electrolytes hyponatremia & hypernatremia
Anatomic Changes and
Clinical Symptoms of
Hyponatremic Encephalopathy
Table 3.
Anatomic Changes
Brain swelling
Pressure on rigid skull
Tentorial herniation
Clinical Symptoms
Headache
Nausea
Vomiting
Seizures
Respiratory arrest
loop diuretics. Vasopressin 2 receptor antagonists are a
promising therapy that are under investigation but are
not approved for clinical use.
Postoperative Hyponatremia
Deaths due to hyponatremic encephalopathy have been
reported in healthy children following routine surgical
procedures. Patients develop hyponatremia postoperatively due to a combination of nonosmotic stimuli for
ADH release, such as subclinical volume depletion, pain,
nausea, stress, edema-forming conditions, and administration of hypotonic fluids. The postoperative nonosmotic stimuli for ADH release usually resolve by the third
postoperative day, but they can persist until the fifth
postoperative day. The most important factors leading to
postoperative hyponatremia are failure to recognize the
compromised ability of the patient to maintain water
balance and the administration of hypotonic fluids. All
postoperative patients should be considered at risk for
developing hyponatremia, and prophylactic measures
should include avoidance of hypotonic fluids and administration of normal saline unless a free water deficit is
present. Serum electrolytes should be monitored postoperatively in patients receiving intravenous fluids, and
physicians should be alert to signs of symptomatic hyponatremia.
can be associated with a variety of illnesses, but most
often it is due to central nervous system disorders, pulmonary disorders, and medications (Table 4). Among
the latter, the chemotherapeutic drugs vincristine and
cyclophosphamide and the antiepileptic drug carbamazepine are especially common. SIADH is essentially a
diagnosis of exclusion. Before it can be diagnosed, diseases causing decreased effective circulating volume, renal impairment, adrenal insufficiency, and hypothyroidism must be excluded. The hallmarks of SIADH are: mild
volume expansion with low-to-normal plasma concentrations of creatinine, urea, uric acid, and potassium;
impaired free water excretion with normal sodium excretion that reflects sodium intake; and hyponatremia that is relatively unresponsive
to sodium administration in the absence
of fluid restriction.
SIADH usually is of short duration
and resolves with treatment of the underlying disorder and discontinuation of the
offending medication. Fluid restriction is
the cornerstone of therapy, but it represents a slow method of correction and
frequently is impractical in infants who
receive most of their nutrition in liquid
form. All intravenous fluids should be of a
tonicity of at least normal saline; if this
does not correct the plasma sodium, 3%
sodium chloride may be administered as
needed. If more rapid correction of hyponatremia is needed, the addition of a loop
diuretic in combination with hypertonic
fluids is useful. Agents that produce diabetes insipidus, such as demeclocycline,
can be used if SIADH persists for more
than 1 month and is unresponsive to fluid
restriction, increased sodium intake, and Figure 2. Effects of physical factors on hyponatremic encephalopathy.
374 Pediatrics in Review Vol.23 No.11 November 2002
fluids & electrolytes hyponatremia & hypernatremia
Table 4.
Causes of SIADH
Central Nervous System Disorders
●
●
●
●
●
●
Infection: meningitis, encephalitis
Neoplasms
Vascular abnormalities
Psychosis
Hydrocephalus
Postpituitary surgery
Pulmonary Disorders
●
●
●
●
●
Pneumonia
Tuberculosis
Asthma
Positive pressure ventilation
Pneumothorax
Carcinomas
●
●
●
●
●
Bronchogenic carcinomas
Oat cell of the lung
Duodenal
Pancreatic
Neuroblastoma
Medications
●
●
●
●
3. Effects
encephalopathy.
Figure
of
hypoxemia
on
Vincristine
Intravenous cyclophosphamide
Carbamazepine
Serotonin reuptake inhibitors
hyponatremic
Oral Water Intoxication in Infants
Water intoxication is one of the most common causes of
symptomatic hyponatremia in healthy infants; 70% of
infants younger than 6 months of age who develop
seizures that have no apparent cause are found to have
hyponatremia due to water intoxication. Most of these
infants are living in poverty and develop water intoxication when caregivers either dilute formula inappropriately or supplement feedings with water. Because an
infant’s caloric intake depends almost entirely on a liquid
diet, hunger will drive the infant to accept a low-solute
formula to the point of water intoxication. Infants typically present with generalized tonic-clonic seizures, respiratory insufficiency, and hypothermia. Affected infants
may be managed with rapid and partial correction of
hyponatremia via administration of hypertonic or normal
saline. The hyponatremia corrects rapidly due to a free
water diuresis, and it corrects spontaneously in many
infants after they resume normal feeding. With appropriate treatment, the prognosis generally is good without
long-term neurologic sequelae.
Diuretics
Diuretics are a relatively common cause of hyponatremia
in children, with severe and symptomatic hyponatremia
occurring primarily in patients receiving thiazide diuretics. Thiazide diuretics can cause both acute and chronic
hyponatremia, but typically hyponatremia develops in
the first few weeks following the initiation of therapy.
Thiazide diuretics frequently are employed to manage
edema-forming states, and the effects of the diuretic are
synergistic with other underlying disorders that cause
hyponatremia. Excess water intake also is a major contributing factor to the development of hyponatremia
among those receiving diuretics.
Treatment
In general, if there are no neurologic manifestations of
hyponatremia, correction with hypertonic saline is unnecessary and potentially harmful. Symptomatic hyponatremia, on the other hand, is a medical emergency. Once
signs of encephalopathy are identified, prompt treatment
is required in a monitored setting before imaging studies
are performed. Fluid restriction alone has no place in the
treatment of symptomatic hyponatremia. Affected paPediatrics in Review Vol.23 No.11 November 2002 375
fluids & electrolytes hyponatremia & hypernatremia
tients should be treated with hypertonic saline (3%) at a
dose of 514 mEq/L administered by an infusion pump.
The rate of infusion should raise the plasma sodium
concentration by about 1 mEq/L (1 mmol/L) per hour
until either the patient becomes alert and seizure-free,
the plasma sodium level increases by 20 to 25 mEq/L
(20 to 25 mmol/L), or a serum sodium concentration
of approximately 125 to 130 mEq/L (125 to
130 mmol/L) is achieved, whichever occurs first. If the
patient is seizing or showing other signs of increased
intracranial pressure, the infusion rate should be increased to raise the serum sodium level by 4 to 8 mEq/L
(4 to 8 mmol/L) during the first hour or until the seizure
activity ceases. Assuming that total body water comprises
50% of total body weight, 1 mL/kg of 3% sodium
chloride in water will raise the plasma sodium by about
1 mEq/L (1 mmol/L).
Cerebral Demyelination
Brain damage and cerebral demyelination can develop if
there is an excessive change in serum sodium levels.
Cerebral demyelinating lesions
are a rare but recognized complication of therapy for hyponatremic encephalopathy. They typically occur several days following
the correction of hyponatremia
and can present with confusion,
quadriplegia, pseudobulbar palsy,
and a pseudocoma with a “locked
in” stare. In many cases, they are
asymptomatic. The lesions are diagnosed best on magnetic resonance imaging performed at least 2 weeks following the correction of
hyponatremia. The incidence of cerebral demyelination is unclear because most reported cases failed to
document the demyelination. Recent data demonstrated that the rate of correction has little or no
relationship to the development of demyelinating lesions; rather, the absolute magnitude of correction
and the underlying illnesses are the major contributing
factors. Hyponatremic patients who develop demyelinating
lesions have either: a) been made hypernatremic inadvertently, b) had their plasma sodium levels corrected by
greater than 25 mmol/L in 24 to 48 hours, c) suffered a
hypoxic event, or d) had severe liver disease. Because the
risk of death and permanent neurologic damage in untreated hyponatremia far exceeds the theoretical possibility
of demyelinating lesions following correction, clinicians
should not hesitate to use hypertonic saline in symptomatic
patients.
Hypernatremia
Hypernatremia is defined as a serum sodium concentration greater than 145 mEq/L (145 mmol/L). In both
children and adults, hypernatremia is seen primarily in
hospitals and occurs in individuals who have restricted
access to water for a variety of reasons. Typically, affected
patients are either debilitated by an acute or chronic
illness, have neurologic impairment, or are at the extremes of age. Infants, especially those born preterm, are
at particularly high risk for the development of hypernatremia because of their relatively small mass-to-surface
area ratio and their dependency on a caretaker to administer fluids. Gastroenteritis remains an important cause of
hypernatremia in children, but it is much less common
than previously reported. Ineffective breastfeeding is a
rare cause of hypernatremia, but the incidence appears to
be increasing. It primarily occurs in primiparous welleducated mothers, who fail to recognize progressive malnutrition and dehydration. Significant vascular complications have been reported in these infants. Unlike mild
chronic hyponatremia, which may be physiologic in certain
Excess
water intake is a major
contributing factor to the development of
hyponatremia among those receiving
diuretics.
376 Pediatrics in Review Vol.23 No.11 November 2002
edematous diseases, a serum sodium concentration greater
than 145 mEq/L (145 mmol/L) always should be considered abnormal and evaluated thoroughly.
Pathogenesis
The body has two defenses to protect against developing
hypernatremia: the ability to produce a concentrated
urine and a powerful thirst mechanism. ADH release
occurs when the plasma osmolality exceeds 275 to
280 mOsm/kg (275 to 280 mmol/kg) and results in a
maximally concentrated urine when the plasma osmolality exceeds 290 to 295 mOsm/kg (290 to 295 mmol/
kg). Thirst is the body’s second line of defense, but it
provides the ultimate protection against hypernatremia.
If the thirst mechanism is intact and access to free water
is unrestricted, it is rare for a person to develop sustained
hypernatremia from either excess sodium ingestion or a
renal concentrating defect.
fluids & electrolytes hyponatremia & hypernatremia
Figure 4. Diagnostic approach to hypernatremia.
Diagnosis
Hypernatremia is usually multifactorial, and a systematic
approach is required to determine the contributing factors (Fig. 4). Serum sodium, glucose, and osmolality
levels must be measured. An elevated serum sodium
concentration always is associated with hyperosmolality
and should be considered abnormal. In cases of significant hyperglycemia, the serum sodium concentration
will be depressed due to the associated translocation of
fluids from the intracellular to extracellular space. Once
hypernatremia has been diagnosed, a detailed history
should be taken and fluid intake reviewed to determine if
the patient has an intact thirst mechanism, has restricted
access to fluids, or is not being provided adequate free
water in intravenous fluids. Urine volume should be
measured and compared with fluid intake, and the urine
osmolality and electrolyte levels should be determined to
assess if the renal concentrating ability is appropriate and
to quantify the urinary free water losses. A less than
maximally concentrated urine (⬍800 mOsm/kg
[800 mmol/L]) in the face of hypernatremia is a sign of
a renal concentrating defect because hypernatremia is a
maximal stimulus for ADH release. For patients who
have hypernatremia, the following should be evaluated:
gastrointestinal losses, dermal losses from fever or burns,
diet history (including enteral feedings), medication history (including diuretics), and sources of exogenous
sodium.
Clinical Manifestations and Mortality
Hypernatremia results in an efflux of fluid from the
intracellular space to the extracellular space to maintain
osmotic equilibrium. This leads to transient cerebral
dehydration and cell shrinkage. Brain cell volume can
decrease by as much as 10% to 15% acutely, but it adapts
quickly. Within 1 hour, the brain significantly increases
its intracellular content of sodium and potassium, amino
acids, and unmeasured organic substances (idiogenic
osmoles). Within 1 week, the brain regains approximately 98% of its water content. If severe hypernatremia
develops acutely, the brain may not be able to increase its
intracellular solute sufficiently to preserve its volume, and
the resulting cellular shrinkage can cause structural
changes. Cerebral dehydration from hypernatremia can
result in a physical separation of the brain from the
meninges, leading to rupture of the delicate bridging
veins and intracranial or intracerebral hemorrhages. Venous sinus thrombosis progressing to infarction also can
develop. Acute hypernatremia also has been shown to
cause cerebral demyelinating lesions in both animals and
humans. Patients who have hepatic encephalopathy are
at the highest risk for developing such lesions.
Children who have hypernatremia usually appear agitated and irritable, but these symptoms can progress to
lethargy, listlessness, and coma. Neurologic examination
frequently reveals increased tone, nuchal rigidity, and
brisk reflexes. Myoclonus, asterixis, and chorea can be
present; tonic-clonic and absence seizures have been
described. Hyperglycemia is a particularly common consequence of hypernatremia in children. Severe hypernatremia also can result in rhabdomyolysis. Although
earlier reports showed that hypocalcemia was associated
with hypernatremia, this has not been found in more
recent literature.
Hypernatremia is associated with a mortality rate of
15% in children, which is estimated to be 15 times higher
than the age-matched mortality in hospitalized children
who do not have hypernatremia. The high mortality rate
Pediatrics in Review Vol.23 No.11 November 2002 377
fluids & electrolytes hyponatremia & hypernatremia
Management of Hypernatremia
circulatory collapse, fluid resuscitation with normal saline or colloid
should be instituted before correctCause
Treatment*
ing the free water deficit. The type
A. Sodium and water loss
0.45% Sodium chloride in 5% dextrose
of therapy depends largely on the
● Gastroenteritis
in water
cause of the hypernatremia and
B. Primary water loss
0.2% Sodium chloride in 5% dextrose in
● Ineffective breastfeeding
water
should be tailored to the pathoC. Nephrogenic diabetes insipidus
0.1% Sodium chloride in 2.5% dextrose
physiologic events involved in each
in water (acute management)
patient (Table 5). Oral hydration
D. Central diabetes insipidus
Desmopressin acetate
should be instituted as soon as it
E. Sodium overload
5% dextrose in water
can be tolerated safely. Plasma elecDiuretics or dialysis may be needed
trolytes should be measured every
*Avoid 5% dextrose in water if hyperglycemia is present.
2 hours until the patient is neurologically stable.
The rate of correction of hyperis unexplained. Most of the deaths are not related directly
natremia depends largely on the severity of hypernatreto central nervous system pathology and appear to be
mia and its cause. Due to the relative inability of the brain
independent of the severity of hypernatremia. Recent
to extrude idiogenic osmoles, rapid correction of hyperstudies have noted that patients who develop hypernatrenatremia can lead to cerebral edema. Although no definmia following hospitalization and patients in whom
itive studies document the optimal rate of correction that
treatment is delayed have the highest mortality. Approxcan be undertaken without developing cerebral edema,
imately 40% of the deaths in children occurred while
empiric data have shown that unless symptoms of hyperpatients were still hypernatremic.
natremic encephalopathy are present, a rate of correction
not exceeding 1 mEq/h or 15 mEq/24 h is reasonable.
Treatment
In severe hypernatremia (sodium, ⬎170 mEq/L
The goal of therapy for hypernatremia is to correct both
[170 mmol/L]), serum sodium should not be corrected
the serum sodium level and the circulatory volume. The
to below 150 mEq/L (150 mmol/L) in the first 48 to
cornerstone is provision of adequate free water to correct
72 hours. It is not uncommon for seizures to occur
the serum sodium level. The free water deficit cannot be
during the correction of hypernatremia; they may be a
assessed easily by physical examination in children who
sign of cerebral edema. They usually can be managed by
have hypernatremic dehydration because most of the
slowing the rate of correction or by administering hyperwater losses are intracellular. Accordingly, the signs of
tonic saline to increase the serum sodium concentration
volume depletion are less pronounced due to better
slightly. The seizures are usually self-limited and not a
preservation of the extracellular volume. A simple
sign of long-term neurologic sequelae. Patients who have
method of estimating the minimum amount of fluid
acute hypernatremia that is corrected by the oral route
necessary to correct the serum sodium is by the following
can tolerate a more rapid rate of correction with a much
equation:
lower incidence of seizures.
Table 5.
Free water deficit (mL) ⫽
4 mL ⫻ lean body weight (kg) ⫻
[desired change in serum sodium mEq/L (mmol/L)]
Larger amounts of fluid will be required, depending
on the fluid composition. To correct a 3-L free water
deficit, approximately 4 L of 0.2% sodium chloride in
water or 6 L of 0.45% sodium chloride in water would be
required because they contain approximately 75% and
50% free water, respectively. The calculated deficit does
not account for insensible losses or ongoing urinary or
gastrointestinal losses. Maintenance fluids, which include
replacement of urine volume with hypotonic fluids, are
given in addition to the deficit. If there are signs of
378 Pediatrics in Review Vol.23 No.11 November 2002
Suggested Reading
Arieff AI. Central nervous system manifestations of disordered
sodium metabolism. Clin Endocrinol Metab. 1984;13:269 –293
Arieff AI, Ayus JC, Fraser CL. Hyponatraemia and death or permanent
brain damage in healthy children. BMJ. 1992;304:1218–1222
Ayus JC, Arieff AI. Chronic hyponatremic encephalopathy in postmenapausal women: association of therapies with morbidity and
mortality. JAMA. 1999;281:2299 –2304
Ayus JC, Arieff AI. Pathogenesis and prevention of hyponatremic
encephalopathy. Endocrinol Metab Clin North Am. 1993;22:
425– 446
Ayus JC, Arieff AI. Pathogenesis and treatment of hypoosmolar and
hyperosmolar states. In: Suki WN, Massry SG, eds. Suki and
fluids & electrolytes hyponatremia & hypernatremia
Massry: Therapy of Renal Diseases and Related Disorders. 3rd ed.
Boston, Mass: Kluwer Academic Publishers; 1997:1–19
Ayus JC, Arieff AI. Pulmonary complications of hyponatremic
encephalopathy: noncardiogenic pulmonary edema and hypercapnic respiratory failure. Chest. 1995;107:517–521
Ayus JC, Krothapalli RK, Arieff AI. Treatment of symptomatic
hyponatremia and its relation to brain damage. A prospective
study. N Engl J Med. 1987;317:1190 –1195
Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med. 1992;
117:891– 897
Bartter FC, Schwartz WB. The syndrome of inappropriate secretion
of antidiuretic hormone. Am J Med. 1967;42:790 – 806
Fraser CL, Arieff AI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997;102:
67–77
Cooper WO, Atherton HD, Kahana M, et al. Increased incidence of
severe breastfeeding malnutrition and hypernatremia in a metropolitan area. Pediatrics. 1995;96:957–960
Keating JP, Schears GJ, Dodge PR. Oral water intoxication in
infants: an American epidemic. Am J Dis Child. 1997;145:
985–990
Moritz ML, Ayus JC. The changing pattern of hypernatremia in
hospitalized children. Pediatrics. 1999;104:435– 439
Morris-Jones PH, Houston IB. Prognosis of the neurological
complication of acute hypernatremia. Lancet. 1967;2:1385–
1389
Rose DR. Hyperosmolal states– hypernatremia. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York,
NY: McGraw-Hill, Inc; 1994:695–736
Rose DR. Hypoosmolal states– hyponatremia. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York,
NY: McGraw-Hill, Inc; 1994:651– 694
Sarnaik AP, Meert K, Hackbarth R, Fleischmann L. Management of
hyponatremic seizures in children with hypertonic saline: a safe
and effective strategy. Crit Care Med. 1994;19:758 –762
Weisberg LS. Pseudohyponatremia: a reappraisal. Am J Med. 1989;
86:315–318
Please note that the deadline for submission of your answer sheets for
the quizzes in the issues of 2002 has been extended to January 31, 2003.
Pediatrics in Review Vol.23 No.11 November 2002 379
fluids & electrolytes hyponatremia & hypernatremia
PIR Quiz
Quiz also available online at www.pedsinreview.org.
1. A 9-month-old girl presents with a 5-day history of severe, watery diarrhea. She is irritable and appears
clinically dehydrated, although less than would be expected from her history. Her mental status
deteriorates, and she appears comatose. Her serum sodium level is 184 mEq/L (184 mmol/L). The most
likely mechanism for this acute change is:
A.
B.
C.
D.
E.
Brainstem herniation.
Cerebral edema.
Cerebral hypoxia.
Demyelination.
Intracranial hemorrhage.
2. A 5-year-old boy in the intensive care unit experiences seizures 2 days following cardiac surgery. His serum
sodium concentration is 117 mEq/L (117 mmol/L). Other expected laboratory values would include:
A. Decreased plasma osmolality (<280 mOsm/kg H2O [280 mmol/kg H2O]); decreased urine osmolality
(<100 mOsm/kg H2O [100 mmol/kg H2O]).
B. Decreased plasma osmolality (<280 mOsm/kg H2O [280 mmol/kg H2O]); increased urine osmolality
(>100 mOsm/kg H2O [100 mmol/kg H2O]).
C. Increased plasma osmolality (>280 mOsm/kg H2O [280 mmol/kg H2O]); decreased urine osmolality
(<100 mOsm/kg H2O [100 mmol/kg H2O]).
D. Increased plasma osmolality (>280 mOsm/kg H2O [280 mmol/kg H2O]); increased urine osmolality
(>100 mOsm/kg H2O [100 mmol/kg H2O]).
E. Normal plasma osmolality; normal urine osmolality.
3. The mother of a 3-month-old boy is concerned that “he is too weak and won’t gain weight!” He was born
at 25 weeks’ gestation and had chronic lung disease that was treated with diuretics. Laboratory studies
demonstrate that he is hyponatremic. The best laboratory study to assess the contributing effect of the
diuretics further is:
A.
B.
C.
D.
E.
Plasma osmolality.
Serum blood urea nitrogen.
Serum creatinine.
Urine osmolality.
Urine sodium.
4. A 9-year-old boy who has cerebral palsy is admitted to the hospital following 4 days of diarrhea. His initial
serum sodium level is 174 mEq/L (174 mmol/L). Once circulatory volume is restored, the primary focus of
the fluid management must be to provide appropriate amounts of:
A.
B.
C.
D.
E.
Chloride.
Free water.
Glucose.
Phosphate.
Potassium.
5. Children who have hypernatremic dehydration often appear minimally dehydrated on clinical examination.
This feature is due to maintenance of:
A.
B.
C.
D.
E.
Extracellular fluid volume.
Intracellular fluid volume.
Total body glucose.
Total body sodium concentration.
Total body water balance.
380 Pediatrics in Review Vol.23 No.11 November 2002