Hypokalemia in children

Authors:Michael J Somers, MDAvram Z Traum, MDSection Editor:Tej K Mattoo, MD,

DCH, FRCPDeputy Editor:Melanie S Kim, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2020. | This topic last updated: Nov 26,
2018.
INTRODUCTION
Hypokalemia is defined as a serum or plasma potassium that is less than the normal
value. Most reference laboratories establish the lower pediatric limit of normal serum
potassium between 3 and 3.5 mEq/L. However, symptoms are unlikely to occur in
most healthy children until serum potassium is below 3 mEq/L.
The etiology, clinical findings, diagnosis, evaluation, and management of pediatric
hypokalemia are reviewed here. Hypokalemia in adults is discussed separately. (See
"Clinical manifestations and treatment of hypokalemia in adults" and "Causes of
hypokalemia in adults" and "Evaluation of the adult patient with hypokalemia".)
EPIDEMIOLOGY
Hypokalemia is relatively common among hospitalized pediatric patients, especially
those who are critically ill [1-3]. In one study of 667 children cared for in a single-
center pediatric intensive care unit in the United States during the calendar year
2006, 40 percent of the patients had a serum potassium level below 3.5 mEq/L [1].
This included patients with severe hypokalemia, defined as potassium level less than
2.5 mEq/L (4 percent); moderate hypokalemia, defined as potassium level 2.5 to less
than 3 mEq/L (12 percent); and mild hypokalemia, defined as potassium level from 3
to less than 3.5 mEq/L (24 percent). Hypokalemia was associated with diagnoses of
cardiac disease, renal failure, or shock [1].
In developing countries, severe hypokalemia (potassium level <2.5 mEq/L) is often
observed in children with diarrhea and severe acute malnutrition, and is associated
with an increased risk of mortality [4].
POTASSIUM BALANCE AND LEVELS
Definition — Potassium is primarily an intracellular cation with cells containing
approximately 98 percent of total body potassium. Hypokalemia is defined as serum
level below the normal value, which is usually defined as 3.5 mEq/L, although the
threshold varies with age (table 1). Degrees of hypokalemia are defined as following:
●
Severe hypokalemia – Potassium level less than 2.5 mEq/L
●
Moderate hypokalemia – Potassium level between 2.5 and 3 mEq/L
●
Mild hypokalemia – Potassium level between 3 and 3.5 mEq/L

Homeostatic mechanisms — Homeostatic mechanisms regulate potassium balance

in order to maintain high intracellular levels required for cellular functions
(metabolism and growth), and low extracellular concentration to preserve the steep
concentration gradient across the cell membrane needed for nerve excitation and
muscle contraction. In children, positive potassium balance is needed for growth,
whereas in adults, homeostasis is directed towards a zero potassium balance.
After a bolus of potassium intake, normal physiologic processes preserve the intra-
and extracellular balance via intracellular potassium movement, which is regulated by
cell membrane Na-K-ATPase (mediated by insulin, and alpha- and beta-2 adrenergic
agonists), and urinary potassium excretion (primarily mediated by aldosterone).
Although normal serum and plasma potassium concentrations in children and
adolescents are similar to levels in adults, infants have a higher normal range of
potassium because of their reduced urinary potassium excretion, which is caused by
their relatively increased aldosterone insensitivity and decreased glomerular filtration
rate (GFR) (table 1). (See "Causes and evaluation of hyperkalemia in adults", section
on 'Brief review of potassium physiology'.)
Pathogenesis of hypokalemia — Hypokalemia in children is caused by
derangements of the hemostatic mechanisms that normally regulate potassium
balance, which are the same as those that occur in adults. Understanding the
underlying physiology is helpful in the diagnostic evaluation and treatment of
children with hypokalemia.
Pediatric hypokalemia is due to one or a combination of the following mechanisms:
●
Decreased potassium intake
●
Increased intracellular movement of potassium
●
Excessive loss of potassium via the gastrointestinal tract, kidney, or skin

CAUSES
In the following sections, the causes of pediatric hypokalemia are classified based on
the underlying pathophysiologic process (table 2).
Decreased intake — Decreased intake alone is unlikely to cause hypokalemia in
healthy children. However, prolonged decreased intake (eg, malnutrition or anorexia)
in combination with increased potassium losses via the kidney or gastrointestinal
tract can lead to significant potassium depletion.
Increased intracellular uptake — As noted above, the normal distribution of
potassium between cells and the extracellular fluid is primarily maintained by the Na-
K-ATPase pump in the cell membrane. Increased activity of the Na-K-ATPase pump
and/or alterations in other potassium transport pathways can result in transient
hypokalemia due to increased potassium entry into cells from the extracellular space.
●
Alkalosis – Either respiratory or metabolic alkalosis can be associated with
hypokalemia. In this setting, intracellular potassium movement is promoted to
maintain electroneutrality as hydrogen ions exit the cell in response to the increase in
extracellular pH. In general, serum potassium concentration falls by less than 0.4
mEq/L for every 0.1 unit rise in pH.

In children with metabolic alkalosis, there is also an increased loss of urinary

potassium. This is due to a rise in plasma bicarbonate concentration, resulting in a
filtered bicarbonate load above its reabsorptive threshold, which leads to increased
distal delivery of sodium bicarbonate. At the distal tubule, sodium is exchanged for
potassium, causing the increased loss in urinary potassium. (See 'Increased distal
delivery of sodium and water' below.)

●
Increased insulin activity – Insulin promotes intracellular potassium movement by
increasing the activity of the Na-K-ATPase pump, and is used therapeutically to treat
severe hyperkalemia [5]. In particular, insulin administration in children with diabetic
ketoacidosis results in a fall in serum potassium due to the increased insulin-
mediated intracellular movement of potassium. One small study also reported that
insulin increased renal potassium excretion [6]. (See "Treatment and complications
of diabetic ketoacidosis in children and adolescents", section on 'Serum potassium'.)
Hypokalemia due to insulin-mediated potassium transcellular movement can also be
seen in the refeeding syndrome after prolonged starvation, or in children and
adolescents with eating disorders [7]. (See "Anorexia nervosa in adults and
adolescents: The refeeding syndrome", section on 'Pathogenesis and clinical
features' and "Poor weight gain in children younger than two years in resource-rich
countries: Management", section on 'Nutritional recovery syndrome (refeeding
syndrome)'.)

●
Elevated beta-adrenergic activity – Nonselective (eg, isoproterenol and
epinephrine) and selective (eg, albuterol and terbutaline) beta-adrenergic agents
promote intracellular movement of potassium by increasing Na-K-ATPase pump
activity. The use of these agents in children can decrease serum potassium levels,
and in some cases, result in hypokalemia [8,9]. (See "Acute asthma exacerbations in
children younger than 12 years: Inpatient management", section on 'Laboratory
studies'.)

●
Hypokalemic periodic paralysis – Hypokalemic periodic paralysis is a rare
neuromuscular condition that presents with sudden episodes of severe muscle
weakness associated with hypokalemia. In these patients, the potassium level can
drop rapidly to below 2 mEq/L. Symptoms may be triggered by events associated
with increased adrenergic tone, such as exercise, stress, and high-carbohydrate
meals.

Hypokalemic periodic paralysis is due to defects in muscle calcium and sodium

channels. Most cases are hereditary and are primarily associated with a mutation in
the gene that codes for the alpha-1 subunit of the dihydropyridine-sensitive calcium
channel in skeletal muscle. These patients typically present in late childhood or
adolescence. Acquired cases have been reported in patients with hyperthyroidism
(referred to as thyrotoxic periodic paralysis), and typically present in older patients
between 20 and 30 years of age. (See "Hypokalemic periodic paralysis" and
"Thyrotoxic periodic paralysis".)

●
 Other drugs (besides beta-adrenergic agonists)

•
Heavy metals– Barium toxicity is a rare cause of hypokalemia, caused by blockade of
potassium channels limiting their efflux from cells. Barium salts are found in fireworks
and rodent toxins [10,11]. Barium sulfate is the formulation used in radiographic
procedures and is not absorbed from the gut. Cesium has been reported as a rare
cause of hypokalemia in adults due to its use as an alternative therapy for cancer, but
has not been reported in children [12].

•
Antipsychotic drugs – Hypokalemia has been reported in association with the use of
risperidone and quetiapine in adults. Given the increasing use of this medication in
children and adolescents, a high index of suspicion should be present in children
with hypokalemia or cardiac arrhythmias who are prescribed these medications. (See
"Causes of hypokalemia in adults", section on 'Antipsychotic drugs'.)

•
Chloroquine intoxication due to intracellular movement of potassium is an uncommon
cause of severe hypokalemia in children [13-16].

Gastrointestinal losses — Gastrointestinal (GI) losses are the most common cause

of hypokalemia in children. In particular, diarrheal potassium content (20 to 50 mEq/
L) is relatively high compared with other body fluids [17]. In developing countries,
acute diarrhea with hypokalemia is associated with an increased risk of death [4,18].
(See "Approach to the child with acute diarrhea in resource-limited countries",
section on 'Fluid and electrolytes'.)
In contrast, upper GI losses (eg, vomiting, nasogastric drainage) are initially minimal
as the potassium content is relatively low (5 to 10 mEq/L). However, the loss of
gastric secretions results in metabolic alkalosis that leads to increased urinary
potassium losses. As noted above, metabolic alkalosis leads to increased distal
delivery of sodium bicarbonate, which in combination with hypovolemia-induced
hyperaldosteronism results in enhanced potassium excretion as potassium is
exchanged for sodium. (See 'Increased distal delivery of sodium and water' below.)
Increased urinary losses — Urinary potassium excretion is primarily due to secretion
of potassium in the distal nephron by the principal cells in the connecting tubule and
cortical collecting tubule. In the distal tubule, sodium is reabsorbed under the
influence of mineralocorticoids (primarily aldosterone) and potassium is exchanged
to preserve electroneutrality. Increased urinary potassium loss contributing to
hypokalemia is typically due to one or both of the following mechanisms:
●
Increased delivery of sodium and water to the distal nephron
●
Increased mineralocorticoid activity

Increased distal delivery of sodium and water — In children, the following

conditions are associated with urinary potassium losses leading to lower serum
potassium as a result of increased distal delivery of sodium.
●
Diuretics – Diuretic therapy (loop and thiazide diuretics) impairs sodium
reabsorption in more proximal nephron segments leading to distal delivery of sodium.
In addition, volume depletion leads to increased aldosterone activity.

●
Nonreabsorbable ions – Nonreabsorbable anions are accompanied by sodium,
resulting in distal delivery of sodium, which is exchanged with potassium. Pediatric
settings, in which the presence of nonreabsorbable anions results in increased distal
delivery of sodium, include excess filtered bicarbonate in patients with excessive
vomiting or with proximal (type 2) renal tubular acidosis (RTA), beta-hydroxybutyrate
in patients with diabetic ketoacidosis, and hippurate following toluene abuse (glue-
sniffing). (See 'Gastrointestinal losses' above and "Diabetic ketoacidosis and
hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and
diagnosis", section on 'Serum potassium' and "Inhalant abuse in children and
adolescents", section on 'Hypokalemia'.)

●
Osmotic diuresis – Osmotic diuresis can also result in increased distal delivery of
sodium, resulting in hypokalemia. This is most commonly seen in children with
diabetic ketoacidosis who have glucose osmotic diuresis due to glycosuria, because
the filtered glucose load exceeds the proximal tubular reabsorptive capacity.
Administration of mannitol is a less frequent cause of hypokalemia due to osmotic
diuresis. Hypovolemia may also result from osmotic diuresis if there is inadequate
fluid replacement, which leads to increased aldosterone activity and enhanced distal
potassium secretion. (See 'Increased mineralocorticoid activity' below.)

●
Genetic tubular disorders – Bartter and Gitelman syndromes are autosomal
recessive diseases that are caused by mutations in genes encoding tubular transport
proteins involved in sodium reabsorption. In these patients, sodium absorption is
disrupted leading to increased distal delivery of sodium, resulting in metabolic
alkalosis and hypokalemia, similarly to findings seen in patients who receive chronic
diuretic therapy. In addition, the volume depletion leads to increased levels of renin
and aldosterone, which further enhances urinary potassium losses. (See "Bartter and
Gitelman syndromes".)

●
Tubular injury – Tubular injury due to tubulointerstitial diseases or cisplatin results in
decreased sodium reabsorption in more proximal nephron segments, leading to
distal delivery of sodium, where potassium is exchanged for sodium. In one small
case series of pediatric patients, tubulopathy due to cisplatin, which resulted in
reduced potassium, persisted for months to years following completion of
chemotherapy [19]. (See "Cisplatin nephrotoxicity", section on 'Salt wasting'.)

Distal (type 1) renal tubular acidosis (RTA) — In distal (type 1) RTA, increased
urinary potassium loss is due to enhanced potassium secretion needed to maintain
electroneutrality because of the impaired distal acidification (ie, defective secretion
of protons) (table 3). In addition, tubular cellular membrane permeability is also
increased, leading to potassium loss into the lumen along with protons. In contrast
with proximal (type 2) RTA, as noted above, urinary potassium loss is due to
increased distal delivery of sodium bicarbonate due to the reduced proximal tubule's
absorptive capacity for bicarbonate. (See "Etiology and clinical manifestations of
renal tubular acidosis in infants and children" and 'Increased distal delivery of sodium
and water' above.)
Increased mineralocorticoid activity — Increased mineralocorticoid activity
enhances potassium urinary excretion.
Hypovolemia — In children, the most common cause of increased mineralocorticoid
activity is secretion of aldosterone (hyperaldosteronism) in response volume
depletion.
Other etiologies — Other pediatric causes of increased mineralocorticoid activity
are rare and include:
●
Aldosterone-secreting adenomas. (See "Clinical presentation and evaluation of
adrenocortical tumors", section on 'Adrenocortical adenomas'.)

●
Glucocorticoid remediable aldosteronism (GRA) is an autosomal dominant disorder
due to a fusion of the promoter of the gene encoding aldosterone synthase in the
adrenal zona fasciculata (involved in cortisol synthesis) with the coding region of the
related gene in the zona glomerulosa (involved in aldosterone synthesis). This
mutation increases the production of aldosterone, which can be suppressed by
glucocorticoid administration. GRA typically presents with hypertension before 21
years of age. The potassium level is normal in the majority of patients, and if
hypokalemia is present, it is usually mild. (See "Familial hyperaldosteronism", section
on 'Familial hyperaldosteronism type I (FH type I) or glucocorticoid-remediable
aldosteronism (GRA)'.)

●
Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder due to
mutations of the gene that encodes 11-beta-hydroxysteroid dehydrogenase type 2
isoform, which normally breaks down cortisol to cortisone. This genetic defect
results in increased levels of renal cortisol, which binds to the mineralocorticoid
receptor. AME typically presents in infancy or early childhood with severe
hypertension, failure to thrive, and muscle weakness due to hypokalemia. Chronic
ingestion of licorice containing glycyrrhetinic acid has a similar effect. (See
"Apparent mineralocorticoid excess syndromes (including chronic licorice
ingestion)".)

●
Although the most common form of congenital adrenal hyperplasia (21-hydroxylase
deficiency) leads to decreased aldosterone synthesis and hyperkalemia, other rarer
forms of congenital adrenal hyperplasia are associated with increased
mineralocorticoid synthesis and hypokalemia. These include 17-alpha-hydroxylase
deficiency, which presents with hypertension, hypokalemia, and hypogonadism at
puberty, and 11-beta-hydroxylase deficiency, which presents in neonates with
virilization, hypertension, and hypokalemia. (See "Uncommon congenital adrenal
hyperplasias", section on 'CYP17A1 deficiencies' and "Uncommon congenital adrenal
hyperplasias", section on '11-beta-hydroxylase deficiency'.)

Other causes of urinary loss

Amphotericin B nephrotoxicity — Amphotericin B causes hypokalemia by disrupting
cellular membranes and increasing membrane permeability. Potassium flows down
its concentration gradient out of tubular epithelial cells into the lumen. A large study
in adults comparing conventional amphotericin with the liposomal form found a
significant reduction in hypokalemia from 11.6 to 6.7 percent [20]. A review of
children outside of the neonatal period receiving amphotericin found hypokalemia to
be present in 47 percent of those measured, but none of those receiving liposomal
amphotericin [21]. (See "Amphotericin B nephrotoxicity".)
Liddle syndrome — Liddle syndrome is caused by an autosomal dominant, gain-of-
function mutation in subunits of the epithelial sodium channel (ENaC) that presents
in childhood as hereditary hypokalemic metabolic alkalosis and hypertension. This
genetic disorder has similar findings to apparent mineralocorticoid excess. (See
"Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and
pseudohypoaldosteronism type 1".)
Cystic fibrosis and skin losses — Electrolyte abnormalities including hypokalemia
have been reported in patients with cystic fibrosis [22]. These findings typically
occur in young children less than 2.5 years of age with volume depletion, and often
prior to making the diagnosis of cystic fibrosis.
CLINICAL MANIFESTATIONS
Clinical manifestations vary depending on the severity and acuity of hypokalemia.
Symptoms generally do not become manifest until the serum potassium is below 3
mEq/L unless there is a rapid significant fall in serum potassium.
Clinical findings include:
●
Muscle weakness and paralysis
●
Cardiac arrhythmias and electrocardiogram (ECG) changes
●
Polyuria due to impaired urinary concentrating ability

Neuromuscular and cardiac symptoms induced by hypokalemia are related to

alterations in the generation of the action potential, which is dependent on the
transcellular potassium gradient. (See "Clinical manifestations and treatment of
hypokalemia in adults", section on 'Pathogenesis of symptoms'.)
Muscular weakness — Hypokalemia can induce skeletal muscle weakness and, in
some severe cases, paralysis. Patients are generally asymptomatic until the
potassium drops below 2.5 mEq/L or at higher levels if there is a sudden precipitous
drop in potassium. Muscle weakness typically starts in the proximal muscles of the
lower extremities and progresses upwards to the trunk and upper extremities. As the
potassium drops below 2 mEq/L, severe weakness progresses, involving respiratory
muscles, which may result in respiratory failure and death.
Hypokalemia can also induce smooth muscle weakness, which is manifested as ileus
[23]. Affected patients may complain of abdominal distension, anorexia, nausea,
vomiting, and/or constipation.
In addition to causing muscle weakness, severe potassium depletion (serum
potassium less than 2.5 mEq/L) can lead to muscle cramps and/or fasciculations,
rhabdomyolysis, and myoglobinuria. A potential diagnostic problem is that the
release of potassium from the cells with rhabdomyolysis can mask the severity of the
underlying hypokalemia with misleading values of normal or high serum/plasma
values. (See "Causes of rhabdomyolysis" and "Causes of rhabdomyolysis", section
on 'Electrolyte disorders'.)
Cardiac findings — Hypokalemia may adversely affect the cardiac conduction,
resulting in arrhythmias including premature atrial and ventricular complex beats,
sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block,
and ventricular tachycardia or fibrillation. Hypokalemia is also associated with
characteristic ECG changes including PR prolongation, flattening of T waves, and ST
depression. With more profound hypokalemia, U waves can emerge after the T
waves, as best seen in the precordial leads (waveform 1) [23,24]. (See "Clinical
manifestations and treatment of hypokalemia in adults", section on 'Cardiac
arrhythmias and ECG abnormalities'.)
Renal manifestations — Prolonged hypokalemia can cause renal dysfunction,
particularly impaired concentrating ability that presents as polyuria and/or
polydipsia. (See "Hypokalemia-induced renal dysfunction".)
DIAGNOSIS
The diagnosis of hypokalemia is made by the detection of a plasma or serum
potassium level that is below the normal range, usually 3.5 mEq/L. In infants, the
normal range of potassium is greater than in older children and adults because of
their reduced urinary potassium excretion (table 1). In many instances, the diagnosis
is made incidentally when plasma or serum electrolytes are obtained during an
evaluation for another condition, especially in children with levels between 3 and 3.5
mEq/L, whereas levels below 3 mEq/L are more often associated with clinical signs
and symptoms.
It is important to note that potassium levels may vary by measurement technique.
Normal values are typically based on measurements from central hospital automated
blood biochemistry autoanalyzers. In intensive care unit and emergency department
settings, there is increasing utilization of point-of-care testing blood chemistry
analyzers that allow rapid and accurate assessment of potassium levels from whole
blood samples, with results that are similar to those found with blood gas analyzers
[25]. However, one study in children reported potassium levels were lower by a mean
difference of 0.4 mEq/L when measured by blood gas analyzers compared with
values obtained from the central laboratory [26]. These differing results may be due
to the use of different blood gas analyzers. Clinicians should be aware of these
differences in their own institutions before interpreting potassium measurements
based on blood gas results.
Of note, serum or plasma potassium is not reflective of total potassium stores, as 98
percent of potassium is intracellular. Settings in which there is a transcellular
movement of potassium into the cell can lead to the false assumption of total body
potassium depletion. This may lead to unnecessary potassium repletion rather than
correcting the underlying cause of increased intracellular potassium uptake (eg,
alkalosis or administration of insulin). Conversely, a normal or elevated potassium
level in a setting of potassium movement out of the cell (eg, diabetic ketoacidosis)
may mask true total body potassium depletion.
EVALUATION TO DETERMINE UNDERLYING ETIOLOGY
Because severe hypokalemia is a potentially life-threatening condition, initial
management takes precedence over any diagnostic evaluation. The urgency and
type of intervention are based on the magnitude of the potassium deficit and
presence of symptoms.
History — The history often clearly points to the underlying etiology, and there is
little need for further extensive diagnostic evaluation.
Historical clues include the following:
●
Acute gastrointestinal (GI) illness with diarrhea or vomiting is the most common
cause of hypokalemia in otherwise healthy children.
 ●
Decreased dietary potassium intake is typically not the main cause of hypokalemia,
but may be an exacerbating factor, particularly in children with acute GI illness and
potassium loss. (See 'Decreased intake' above.)

●
The use of medications that may promote intracellular potassium uptake (adrenergic
agents [albuterol] or exogenous insulin), or increase renal potassium excretion (eg,
diuretics). (See 'Causes' above.)

●
A positive family history of periodic paralysis or muscle weakness is suggestive of a
genetic form of periodic paralysis. (See "Hypokalemic periodic paralysis".)

●
A diagnosis of thyrotoxic periodic paralysis should be considered in any patient with
concomitant or preceding symptoms of hyperthyroidism (weight loss, heat
intolerance, tremor, palpitations, anxiety, increased frequency of bowel movements,
and shortness of breath). (See "Thyrotoxic periodic paralysis".)

●
History of recurrent hypokalemia is suggestive of an underlying chronic pathologic
condition, which warrants further evaluation.

Physical examination — Once hypokalemia has been discerned, the initial physical

assessment should include the following:
●
Cardiac rate and rhythm by auscultation to screen for arrhythmias.

●
Muscle strength and tone.

●
Reflexes.
 ●
Evaluation of the effective circulating volume and respiratory status. These factors
influence initial management strategies and can prove useful in clarifying acid-base
and volume balance in children with unclear origin of their hypokalemia.

Laboratory studies — In symptomatic cases or if there is any concern for a cardiac

arrhythmia, an electrocardiogram (ECG) should be performed, and treatment should
be immediately started to address any clinically significant findings.
In the child with relatively mild hypokalemia with a history of present illness that
suggests a clear etiology such as viral GI illness or diuretic therapy, there is little
utility to an extensive laboratory evaluation.
If the cause of hypokalemia is uncertain, laboratory evaluation initially focuses on
assessing whether or not there is excessive renal potassium loss (table 4 and
algorithm 1).
Urinary potassium excretion — The most common pediatric cause of increased
urinary potassium excretion is hypovolemia, which results in increased
mineralocorticoid activity due to secretion of aldosterone (hyperaldosteronism). In
these children, hypokalemia and increased urinary potassium renal excretion resolve
with fluid and potassium repletion. (See "Treatment of hypovolemia (dehydration) in
children".)
Other causes of excessive renal potassium losses are less common and are also less
likely to have rapid improvement to a normal potassium level with replacement
therapy. In addition, unless the underlying etiology is addressed (eg, chronic diuretic
therapy or renal tubular acidosis [RTA]), potassium levels will usually fall again, once
supplementation is withdrawn. (See 'Increased urinary losses' above and "Clinical
manifestations and treatment of hypokalemia in adults", section on 'Ongoing losses
and the steady state'.)
Urinary potassium excretion is assessed using spot urine samples obtained
concomitantly with serum chemistries (table 4). Although 24-hour urine collections
will give the most accurate picture of renal potassium handling, these are difficult to
perform in many children and delay establishment of a diagnosis.
●
Random urinary potassium levels <15 to 20 mmol/L should be seen in the setting of
serum potassium levels <3 mmol/L. Substantially higher levels suggest excessive
renal potassium losses.
 ●
Random levels are on occasion misleading, since spot values are influenced by water
excretion at that time. In states of polyuria, spot urinary potassium levels may be
lower than if urine output were normal. In states of decreased urine flow, random
levels may appear >20 mmol/L even though overall daily potassium excretion is being
appropriately conserved.

●
Spot potassium-to-creatinine ratios correct for any variations in urine volume in
patients with stable glomerular filtration rate. A urine potassium-to-creatinine ratio
should be <15 mEq/g creatinine (<1.5 mEq/mmol creatinine) when hypokalemia is
due to GI losses, poor intake, cellular shift, or diuretic use. Ratios >15 mEq/g
creatinine in the setting of a low serum potassium suggest pathologic urinary losses
either due to increased mineralocorticoid activity or tubular dysfunction. (See
"Evaluation of the adult patient with hypokalemia", section on 'Urine potassium-to-
creatinine ratio'.)

Further evaluation — For those children with hypokalemia and excessive urinary

potassium excretion without an apparent etiology, further evaluation is warranted
and is based on the presence or absence of an elevated blood pressure (algorithm
1).
●
For hypertensive patients, plasma renin and aldosterone are obtained.

•
Low renin and high aldosterone levels are suggestive of primary hyperaldosteronism
(adrenal abnormalities). Metabolic alkalosis is also observed in these patients.

•
Low renin and low aldosterone are suggestive of one of the following:

-
Increased activity of another mineralocorticoid that is not aldosterone (eg, apparent
mineralocorticoid excess and some forms of congenital adrenal hyperplasia) (see
'Other etiologies' above)
 -
Liddle syndrome due to enhanced sodium tubular resorption (see 'Liddle syndrome'
above and "Genetic disorders of the collecting tubule sodium channel: Liddle's
syndrome and pseudohypoaldosteronism type 1")

●
For normotensive patients, evaluation focuses on the acid-base status of the patient
as determined by venous pH and serum electrolytes (table 5).

•
For patients with metabolic acidosis, diagnostic possibilities include types I and II
RTA and diabetic ketoacidosis.

•
For patients with metabolic alkalosis, diagnostic possibilities include chronic diuretic
use, persistent vomiting, and the genetic tubulopathies of Bartter and Gitelman
syndromes. Measurement of urinary chloride concentration may be helpful in
differentiating among these disorders.

-
Urinary chloride concentration is normal in Bartter or Gitelman syndromes (see
"Bartter and Gitelman syndromes")

-
Urinary chloride concentration is low in patients with vomiting.

-
Urinary chloride concentration is variable with diuretic therapy depending on
whether tubular function is still responsive to diuretic activity.

•
In patients who have no underlying acid-base disorders, diagnostic possibilities
include magnesium depletion or osmotic diuresis. (See "Hypomagnesemia: Clinical
manifestations of magnesium depletion", section on 'Hypokalemia'.)

●
Although genetic testing can be performed for the rare genetic potassium-wasting
disorders of Bartter, Gitelman, and Liddle syndromes, other clinical findings that are
suggestive of these diagnoses should be present prior to genetic testing. These
entities are discussed in greater detail separately. (See "Bartter and Gitelman
syndromes" and "Genetic disorders of the collecting tubule sodium channel: Liddle's
syndrome and pseudohypoaldosteronism type 1".)

MANAGEMENT
Overview — The acuity and degree of the hypokalemia influence the clinical
approach to therapy. The goals of therapy are to prevent or treat life-threatening
complications (arrhythmias, paralysis, rhabdomyolysis, and diaphragmatic
weakness) associated with severe hypokalemia, replace the potassium deficit, and
correct the underlying cause. The urgency of therapy depends upon the severity of
hypokalemia, and the rate of decline in serum potassium concentration. Lower grade
hypokalemia (serum/plasma potassium between 2.5 and 3 mEq/L) or chronic
hypokalemia at lower levels tend to be better tolerated by the patient and are less
likely to require urgent interventions.
The management of pediatric hypokalemia includes:
●
Ascertaining the need for potassium replacement.

●
Identifying and, if possible, treating the underlying cause of hypokalemia (eg,
hypomagnesemia).

●
Use of potassium-sparing diuretic therapy for patients with chronic renal wasting
conditions, for which there is no treatment for the underlying disorder (Bartter or
Gitelman syndrome).

●
Electrocardiographic monitoring for symptomatic children and those in whom there is
a concern for cardiac arrhythmia.

●
In patients receiving intravenous (IV) fluid a saline without dextrose solution should
be used for initial therapy since the administration of dextrose stimulates the release
of insulin which drives extracellular potassium into the cells. This can lead to a
transient 0.2 to 1.4 mEq/L reduction in the serum potassium concentration,
particularly if the solution contains only 20 mEq/L of potassium [27,28]. The transient
reduction in serum potassium can induce arrhythmias in susceptible patients.

Potassium supplementation
Determining need and timing — The rapidity of potassium supplementation is
dependent on the severity of hypokalemia based on the presence or absence of
symptoms.
●
In symptomatic patients (arrhythmias, marked muscle weakness, or paralysis), rapid
potassium supplementation should be provided. In some cases, this requires IV
administration of potassium chloride, particularly in those who are unable to take oral
medications. In this setting, an infusion with a potassium concentration of no more
than 40 mEq/L is given at a rate not to exceed 0.5 to 1 mEq/kg of body weight per
hour. The goal is to raise the potassium level by 0.3 to 0.5 mEq/L. These patients
require continuous electrocardiographic (ECG) monitoring to detect changes due to
hypokalemia, and also possibly rebound hyperkalemia during replacement therapy.
(See 'Clinical manifestations' above and "Causes, clinical manifestations, diagnosis,
and evaluation of hyperkalemia in children", section on 'Cardiac conduction
abnormalities'.)

●
In asymptomatic patients with potassium levels less than 3 mEq/L, replacement of
potassium stores is generally needed. Oral therapy is preferred and IV
supplementation should be reserved for those who are unable to take oral
medications. The amount of replacement therapy is dependent on the cause of the
hypokalemia, presence of any acid-base disorder, and ongoing excessive losses. In
particular, supplementation may not be needed in patients whose hypokalemia was
caused by transient cellular uptake (eg, limited exposure to beta-adrenergic agents
or exogenous insulin), as correction of the underlying cause results in resolution of
hypokalemia.

●
In asymptomatic patients with acute hypokalemia and potassium levels between 3
and 3.5 mEq/L, correction of the underlying cause and dietary potassium are usually
sufficient without the need for additional potassium supplementation. For those who
are unable to take enteral potassium, the addition of maintenance amount of
potassium to intravenous fluids is usually sufficient.

●
In asymptomatic patients with chronic hypokalemia, potassium supplementation may
be needed, particularly if the underlying cause is not amenable to correction (eg,
types I and II RTA). (See "Treatment of distal (type 1) and proximal (type 2) renal
tubular acidosis".)

Route — Potassium can be administered either enterally or intravenously. Whenever

possible, potassium supplementation should be given enterally. Data in children
cared for in a cardiac intensive care unit have shown that enteral administration has
comparable efficacy and fewer side effects than IV administration [29].
The main concern about the use of IV potassium supplementation is the inadvertent
administration of a large amount of potassium in a short period of time, resulting in
hyperkalemia. Safety measures to prevent this complication include limiting the
absolute amount of potassium in any single container or bag of fluid, and using an
infusion pump. IV potassium administration is also associated with pain and phlebitis
when administered through a peripheral vein, which can be minimized if the
potassium content of the infusion is less than 20 mEq/L. Central venous access is
needed if the potassium concentration exceeds 40 mEq/L.
Formulation — Potassium supplementation commonly comes in five preparations:
potassium chloride, potassium phosphate, potassium acetate, potassium citrate-
citric acid, and potassium bicarbonate.
●
Potassium chloride tends to result in quicker potassium repletion per dose than
phosphate or citrate [30] and is the most common pharmacologic supplement. It is
also preferred in patients with concomitant hypochloremia or metabolic alkalosis.

●
Potassium phosphate is often used in the setting of proximal tubule dysfunction,
such as Fanconi syndrome or cystinosis, where there is loss of both potassium and
phosphorus. It may be used preferentially in children with diabetic ketoacidosis
(DKA) with symptomatic hypophosphatemia.
 ●
Potassium acetate is also commonly used in DKA, allowing for correction of
hypokalemia as well as acidosis upon the metabolism of acetate to bicarbonate.

●
Potassium citrate-citric acid or bicarbonate is generally used in children with
hypokalemia and acidosis, as seen in types I and II renal tubular acidosis (RTA).

Magnesium depletion — Hypomagnesemia may accompany hypokalemia.

Magnesium can be lost at the same time as potassium with gastrointestinal (GI)
losses or with diuretic use. Hypomagnesemia can also promote renal potassium
wasting directly in the distal tubule, and can also prevent reabsorption of filtered
potassium at the loop of Henle [24]. Magnesium supplementation may need to be
considered in this setting, especially with difficulty correcting hypokalemia. (See
"Hypomagnesemia: Clinical manifestations of magnesium depletion", section on
'Hypokalemia'.)
Potassium-sparing diuretics — Potassium supplementation by itself is less effective
in tubulopathies such as Bartter or Gitelman syndromes, where there is ongoing
renal wasting of potassium. Use of a potassium-sparing diuretic such as amiloride
may attenuate these losses. (See "Bartter and Gitelman syndromes", section on
'NSAIDs and drugs that block distal tubule sodium-potassium exchange'.)
Children with hyperaldosteronism may benefit from spironolactone or eplerenone
therapy to reduce the urinary potassium effect of aldosterone. (See "Treatment of
primary aldosteronism", section on 'First line: Mineralocorticoid receptor
antagonists'.)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more detailed.
These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)
●
Basics topic (see "Patient education: Hypokalemia (The Basics)")

SUMMARY AND RECOMMENDATIONS

●
Hypokalemia is defined as a serum or plasma potassium level below the normal
value, which is usually defined as 3.5 mEq/L. Normal serum potassium
concentrations in children and adolescents are similar to levels in adults. However,
infants have a higher normal range of potassium because of their reduced urinary
potassium excretion, caused by their relatively increased aldosterone insensitivity
and decreased glomerular filtration rate (table 1).

●
Pediatric hypokalemia is caused by derangements of the normal hemostatic
mechanisms that regulate potassium balance, and include the following (table 2):

•
Decreased dietary potassium intake is unlikely to cause hypokalemia in healthy
children. However, prolonged decreased intake can contribute to potassium
depletion caused by other disorders.

•
Intracellular potassium uptake results in transient hypokalemia. Increased potassium
entry into the cells is promoted by the following conditions: alkalosis, increased
insulin activity (eg, exogenous insulin administration) and beta-adrenergic activity
(eg, albuterol administration), and hypokalemic periodic paralysis. (See 'Increased
intracellular uptake' above.)

•
Increased gastrointestinal loss is the most common cause of pediatric hypokalemia.

•
Increased urinary losses is usually due to either increased delivery of sodium to the
distal nephron in exchange for potassium (eg, diuretic therapy, genetic tubular
disorders [Bartter and Gitelman syndromes], and osmotic diuresis) or increased
mineralocorticoid activity (eg, hyperaldosteronism due to hypovolemia). (See
'Increased urinary losses' above.)

●
Clinical manifestations vary depending on the severity and acuity of hypokalemia.
Symptoms generally do not become manifest until the serum potassium is below 3
mEq/L unless there is a rapid significant fall in serum potassium. Clinical findings
include muscle weakness and paralysis, cardiac arrhythmias and electrocardiogram
(ECG) changes (waveform 1), and polyuria due to impaired urinary concentration.
(See 'Clinical manifestations' above.)

●
The diagnosis of hypokalemia is made by the detection of a serum or plasma
potassium level that is below the normal range of 3.5 mEq/L. In many instances, the
diagnosis is made incidentally when serum or plasma electrolytes are obtained
during an evaluation for another condition, especially in children with levels between
3 and 3.5 mEq/L, whereas levels below 3 mEq/L are more often associated with
clinical signs and symptoms. (See 'Diagnosis' above.)

●
After acute management of symptomatic severe hypokalemia, further evaluation
focuses on determining the etiology, as subsequent care is based on the underlying
cause of hypokalemia. The assessment includes a focused history and physical
examination. In most cases, the history is sufficient to determine the underlying
cause. However, additional laboratory testing may be needed in patients in whom the
diagnosis remains uncertain (algorithm 1). (See 'Evaluation to determine underlying
etiology' above.)

●
The acuity and degree of the hypokalemia influence the clinical approach to therapy.
The goals of therapy are to prevent or treat life-threatening complications
(arrhythmias, paralysis, rhabdomyolysis, and diaphragmatic weakness) associated
with severe hypokalemia, replace the potassium deficit, and correct the underlying
cause. (See 'Management' above.)

●
Patients with severe or symptomatic hypokalemia (arrhythmias, marked muscle
weakness, or paralysis) require urgent potassium supplementation. For these
patients, we recommend intravenous (IV) administration of potassium chloride,
particularly in those who are unable to take oral medication (Grade 1B). In this
setting, an infusion with a potassium concentration of no more than 40 mEq/L is
given at a rate not to exceed 0.5 to 1 mEq/kg of body weight per hour. The goal is to
raise the potassium level by 0.3 to 0.5 mEq/L. These patients require continuous ECG
monitoring to detect changes due to hypokalemia, and also possibly rebound
hyperkalemia during replacement therapy. (See 'Determining need and timing'
above.)

●
In asymptomatic patients, the need for potassium supplementation is based on the
underlying cause and the severity of hypokalemia. If potassium supplementation is
needed, we recommend that oral potassium therapy be given (Grade 1B). The
formulation of potassium is also dependent on the underlying condition. (See
'Formulation' above and 'Determining need and timing' above.)

REFERENCES
1. Cummings BM, Macklin EA, Yager PH, et al. Potassium abnormalities in a
pediatric intensive care unit: frequency and severity. J Intensive Care Med
2014; 29:269.
2. Singhi S, Marudkar A. Hypokalemia in a pediatric intensive care unit. Indian
Pediatr 1996; 33:9.
3. Subba Rao SD, Thomas B. Electrolyte abnormalities in children admitted to
pediatric intensive care unit. Indian Pediatr 2000; 37:1348.
4. Talbert A, Thuo N, Karisa J, et al. Diarrhoea complicating severe acute
malnutrition in Kenyan children: a prospective descriptive study of risk factors
and outcome. PLoS One 2012; 7:e38321.
5. Moore RD. Stimulation of Na:H exchange by insulin. Biophys J 1981; 33:203.
6. Carlotti AP, St George-Hyslop C, Bohn D, Halperin ML. Hypokalemia during
treatment of diabetic ketoacidosis: clinical evidence for an aldosterone-like
action of insulin. J Pediatr 2013; 163:207.
 7. Fuentebella J, Kerner JA. Refeeding syndrome. Pediatr Clin North Am 2009;
56:1201.
8. Habashy D, Lam LT, Browne GJ. The administration of beta2-agonists for
paediatric asthma and its adverse reaction in Australian and New Zealand
emergency departments: a cross-sectional survey. Eur J Emerg Med 2003;
10:219.
9. Krebs SE, Flood RG, Peter JR, Gerard JM. Evaluation of a high-dose continuous
albuterol protocol for treatment of pediatric asthma in the emergency
department. Pediatr Emerg Care 2013; 29:191.
10. Deepthiraju B, Varma PR. Barium toxicity a rare presentation of fireworks
ingestion. Indian Pediatr 2012; 49:762.
11. Glauser J. Cardiac arrhythmias, respiratory failure, and profound hypokalemia
in a trauma patient. Cleve Clin J Med 2001; 68:401, 405.
12. Melnikov P, Zanoni LZ. Clinical effects of cesium intake. Biol Trace Elem Res
2010; 135:1.
13. Yanturali S, Aksay E, Demir OF, Atilla R. Massive hydroxychloroquine overdose.
Acta Anaesthesiol Scand 2004; 48:379.
14. Marquardt K, Albertson TE. Treatment of hydroxychloroquine overdose. Am J
Emerg Med 2001; 19:420.
15. Jordan P, Brookes JG, Nikolic G, Le Couteur DG. Hydroxychloroquine overdose:
toxicokinetics and management. J Toxicol Clin Toxicol 1999; 37:861.
16. McKenzie AG. Intensive therapy for chloroquine poisoning. A review of 29
cases. S Afr Med J 1996; 86:597.
17. Molla AM, Rahman M, Sarker SA, et al. Stool electrolyte content and purging
rates in diarrhea caused by rotavirus, enterotoxigenic E. coli, and V. cholerae in
children. J Pediatr 1981; 98:835.
18. Butler T, Islam M, Azad AK, et al. Causes of death in diarrhoeal diseases after
rehydration therapy: an autopsy study of 140 patients in Bangladesh. Bull World
Health Organ 1987; 65:317.
19. Bianchetti MG, Kanaka C, Ridolfi-Lüthy A, et al. Persisting renotubular sequelae
after cisplatin in children and adolescents. Am J Nephrol 1991; 11:127.
20. Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical
therapy in patients with persistent fever and neutropenia. National Institute of
Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 1999;
340:764.
21. Dutta A, Palazzi DL. Risk factors of amphotericin B toxicty in the nonneonatal
21.
pediatric population. Pediatr Infect Dis J 2012; 31:910.
22. Scurati-Manzoni E, Fossali EF, Agostoni C, et al. Electrolyte abnormalities in
cystic fibrosis: systematic review of the literature. Pediatr Nephrol 2014;
29:1015.
23. Linshaw MA. Potassium homeostasis and hypokalemia. Pediatr Clin North Am
1987; 34:649.
24. Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North Am
2005; 23:723.
25. Morimatsu H, Rocktäschel J, Bellomo R, et al. Comparison of point-of-care
versus central laboratory measurement of electrolyte concentrations on
calculations of the anion gap and the strong ion difference. Anesthesiology
2003; 98:1077.
26. Chhapola V, Kanwal SK, Sharma R, Kumar V. A comparative study on reliability
of point of care sodium and potassium estimation in a pediatric intensive care
unit. Indian J Pediatr 2013; 80:731.
27. KUNIN AS, SURAWICZ B, SIMS EA. Decrease in serum potassium
concentrations and appearance of cardiac arrhythmias during infusion of
potassium with glucose in potassium-depleted patients. N Engl J Med 1962;
266:228.
28. Gennari FJ. Hypokalemia. N Engl J Med 1998; 339:451.
29. Moffett BS, McDade E, Rossano JW, et al. Enteral potassium supplementation
in a pediatric cardiac intensive care unit: evaluation of a practice change.
Pediatr Crit Care Med 2011; 12:552.
30. Sanguinetti MC, Jurkiewicz NK. Role of external Ca2+ and K+ in gating of
cardiac delayed rectifier K+ currents. Pflugers Arch 1992; 420:180.
Topic 97159 Version 11.0
© 2020 UpToDate, Inc. All rights reserved.