DEPARTMENT
Pharmacology Continuing Education
Hypokalemia and
Hyperkalemia in Infants and
Children: Pathophysiology
and Treatment
Kayleen Daly, PharmD, & Elizabeth Farrington,
PharmD, FCCP, FCCM, FPPAG, BCPS
ABSTRACT
Section Editors
Teri Moser Woo, PhD, RN, ARNP, CNL, CPNP,
FAANP
Corresponding Editor
Pacific Lutheran University
Tacoma, Washington
Elizabeth Farrington, PharmD, FCCP, FCCM,
FPPAG, BCPS
University of North Carolina, Eshelman School of
Pharmacy
Chapel Hill, North Carolina
New Hanover Regional Medical Center
Wilmington, North Carolina
Brady S. Moffett, PharmD, MPH
Clinical Pharmacy Specialist-Pediatric Cardiology
Texas Children’s Hospital, Department of Pharmacy
Houston, Texas
Kayleen Daly, Pharmacist II, New Hanover Regional Medical
Center, Wilmington, NC.
Elizabeth Farrington, Pharmacist III, Pediatrics, New Hanover
Regional Medical Center, Wilmington, NC.
Conflicts of interest: None to report.
Correspondence: Kayleen Daly, PharmD, New Hanover Regional
Medical Center, 2131 S 17th St, Wilmington, NC 28401; e-mail:
kayleen.daly@nhrmc.org.
0891-5245/$36.00
Copyright Q 2013 by the National Association of Pediatric
Nurse Practitioners. Published by Elsevier Inc. All rights
reserved.
http://dx.doi.org/10.1016/j.pedhc.2013.08.003
486
Volume 27 Number 6
Potassium is the second most abundant cation in the body.
About 98% of potassium is intracellular and that is particularly in the skeletal muscle. Electrical disturbances associated
with disorders of potassium homeostasis are a function of
both the extracellular and intracellular potassium concentrations. Clinical disorders of potassium homeostasis occur with
some regularity, especially in hospitalized patients receiving
many medications. This article will review the pathophysiology of potassium homeostasis, symptoms, causes, and treatment of hypo- and hyperkalemia. J Pediatr Health Care.
(2013) 27, 486-496.
KEY WORDS
Hypokalemia, hyperkalemia, treatment
OBJECTIVES
1. Describe the pathophysiology of potassium homeostasis.
2. Explain the role of potassium in the human body.
3. List the symptoms of hypokalemia and hyperkalemia.
4. Recommend the treatment for hyperkalemia and
explain why one treatment regimen might be preferred over another.
5. Recommend the treatment for hypokalemia and explain when one would use intravenous versus oral
replacement.
Healthy persons are in potassium balance, which
means that the daily intake of potassium is equal to
the amount excreted. In children, normal daily potassium requirements vary by age. However, they are estimated at approximately 2 mEq per 100 kcal of energy
Journal of Pediatric Health Care
BOX 1. Foods high in potassium
Fruits
Bananas, oranges (citrus), cantaloupe, watermelon,
apricots, raisins, prunes, pineapples, cherries, and
tomatoes
Vegetables
Green and leafy, potatoes, avocados, artichokes, lentils,
beets, white mushrooms, and onions
Meats/Fish
All contain potassium (the lowest levels are in chicken liver,
shrimp, and crab)
Breads/Flours
Pumpernickel, buckwheat, and soy
Miscellaneous
Chocolate, cocoa, brown sugar, molasses, nuts, peanut
butter, French fries, and whole milk
Data from Potassium content of selected foods per
common measure, sorted by nutrient content (USDA
National Nutrient Database for Standard Reference,
Released 2012). Retrieved from http://lpi.oregonstate.
edu/infocenter/minerals/potassium/ and Bakris, G. L., &
Olendzki, B. (2012). Patient information: Low potassium
diet. Retrieved from http://www.uptodate.com/contents/
low-potassium-diet-beyond-the-basics.
requirement throughout most of childhood (Linshaw,
1987). An adult’s dietary intake varies from approximately 50 to 150 mEq per day. Potassium is present in
sufficient quantities in most fruits, vegetables, meat,
and fish (Box 1 and Table 1). Nutrition labels typically
do not list the amount of potassium that is present in
foods. In this article we will review a clinical approach
to the treatment of both hyperkalemia and hypokalemia in the pediatric population. Treatment of hyperkalemia in newborns is the same as for infants and
children but may be initiated at a slightly higher serum
potassium level because of differences in normal serum
potassium values in newborns.
PHYSIOLOGY OF POTASSIUM
Potassium is the second most abundant cation in the
body. About 98% of potassium is intracellular, particularly in skeletal muscle, where the concentration ranges
from 140 to 150 mEq/L. Only about 2% of the body’s potassium is in the extracellular fluid, where the concentration is tightly regulated at 3.5 to 5.5 mEq/L (Kraft,
Btaiche, Sacks, & Kudsk, 2005). Therefore a gradient
exists for the diffusion of potassium from intracellular
to extracellular fluid. The gradient is the reverse of
that for sodium, which is present in high extracellular
concentration and low intracellular concentration.
Diffusion occurring along both the sodium and potassium gradients is mainly controlled by the sodium–
potassium–adenosine triphosphate (ATP) pump. This
ion pump uses ATP to pump three sodium ions out of
the cell and two potassium ions into the cell, which crewww.jpedhc.org
TABLE 1. Potassium content in popular foods
and beverages
Food/beverage
Potassium content (mEq)
French fries
Small banana
White mushrooms
Orange juice (200 ml)
Whole milk (200 ml)
Broccoli
Potato chips
Green beans
Milk chocolate bar (20 g)
Onions, cooked
Coca-Cola (200 ml)
17.7
8.6
8.1
7.9
7.7
5.8
5.1
3.9
2.4
1.5
0.1
Data from Potassium content of selected foods per common
measure, sorted by nutrient content (USDA National Nutrient Database for Standard Reference, Released 2012). Retrieved from
http://lpi.oregonstate.edu/infocenter/minerals/potassium/
ates an electrochemical gradient over the cell membrane (Nyirenda, Tang, Padfield, & Seck, 2009). Many
factors affect the activity of this pump, such as insulin,
glucagon, catecholamine, aldosterone, acid-base status, plasma osmolality, and intracellular potassium
levels (Baumgartner, Bailey, & Caudill, 1997). The presence of these pumps and the concentration of potassium inside the cell are critical because potassium
performs an essential role in numerous physiologic
and metabolic processes, including regulation of cell
volume; influencing osmotic balance between cells
and the interstitial fluid; renal function; carbohydrate
metabolism; contraction of cardiac muscle; and the regulation of the electrical action potential across cell
membranes, especially in the myocardium (Schaefer
& Wolford, 2005).
Under normal physiological conditions, 80% of potassium is excreted through the kidneys, with at least
90% actively reabsorbed along the kidney tubule.
About 15% of potassium is excreted in feces, and 5%
is lost in sweat. The balance of both cations, sodium
and potassium, is maintained by the kidneys. The kidneys can adjust to increased intake by increasing potassium excretion, but they cannot prevent depletion in
the absence of potassium ingestion. Most drugs that induce hyperkalemia/hypokalemia alter the renal elimination or reabsorption of potassium, and therefore
the kidney is unable to prevent the electrolyte imbalance. The kidneys of a healthy person usually reabsorb
all but 10% of filtered potassium (Greger & G€
ogelein,
1987). However, during osmotic diuresis, the kidney reabsorbs less potassium, and thus hypokalemia may occur. This mechanism of hypokalemia is seen in persons
with diabetic ketoacidosis.
Clinical disorders of potassium homeostasis occur
with some regularity, especially in hospitalized patients
receiving many medications. Clinically significant
symptoms caused by disturbances in potassium
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487
BOX 2. Causes of hyperkalemia
BOX 3. Drug-induced hyperkalemia
Pseudo hyperkalemia
Increased potassium input
Use of tourniquet when drawing blood
Hemolysis of drawn blood
Leukocytosis (white blood cell count >50,000/mm3 or
thrombocytosis [platelets >1,000,000/mm3])
Potassium chloride supplements (including salt substitutes)
Potassium penicillin
Increased efflux from intracellular fluid
Due to redistribution: acidosis, especially inorganic
Hyperkalemic familial periodic paralysis
Increased potassium load endogenous
Extensive tissue injury, burns, heat stroke, or trauma
Hemolysis
Rhabdomyolysis
Tumor lysis syndromes
Tissue necrosis
Hemolytic uremic syndrome
Decreased potassium output
Potassium sparing diuretics (e.g., spironolactone,
triamterine, and amiloride)
Cyclosporine
Angiotensin-converting enzyme inhibitors
Nonsteroidal antiinflammatory drugs
Heparin
Tacrolimus
Pentamidine
Trimethoprim
Data from Lehnhardt & Kemper (2011).
Increased potassium load exogenous
Diet, dietary salt substitutes
Banked blood transfusions
Gastrointestinal hemorrhage
Poisoning
Decreased excretion with or without increased
intake
Acute renal failure and severe chronic renal failure
Mineralocorticoid deficiency
— Addison’s disease
— Selective aldosterone deficiency
Hyporeninemic hypoaldosteronism
Hereditary enzyme deficiencies
Tubulo-interstitial disease
Type IV renal tubular acidosis
Obstruction
Sickle cell disease
Systemic lupus erythematosus
Data from Lehnhardt & Kemper (2011).
balance are due to potassium’s role in regulating ‘‘biologic electricity.’’ An alteration in electrical conduction
within a nerve or muscle can cause signs and symptoms
that range from subtle muscle weakness to more obvious cardiac arrhythmias.
It is important to point out that the electrical disturbances associated with disorders of potassium homeostasis are a function of both the extracellular and
intracellular potassium concentrations. In clinical
conditions leading to chronic potassium depletion,
both the extracellular and intracellular potassium concentrations will be decreased. In addition, in persons
with chronic potassium depletion, potassium shifts
out of the cells, and thus the alteration in electrical conduction is minimized; therefore, disturbances commonly associated with disorders in potassium balance
are less noticeable or absent. In contrast, acute changes
in potassium homeostasis are much more likely to pro488
Volume 27 Number 6
duce clinically significant signs and symptoms
(Lehnhardt & Kemper, 2011).
Hypokalemia, defined as a serum potassium level 3.5
mEq/L or lower, is perhaps the most common electrolyte abnormality encountered by clinicians (Smellie
et al., 2007). Hyperkalemia is defined in children and
adults as a potassium level greater than 5.5 mEq/L. In
newborns, hyperkalemia is defined as a serum potassium level more than 6 mEq/L. Although hyperkalemia
is less common than hypokalemia, it is equally important by virtue of its inherent dangers.
HYPERKALEMIA
Although hyperkalemia is defined as a serum potassium concentration of > 5.5 mEq/L, it is moderate (6
to 7 mEq/L) and severe (> 7 mEq/L) cases of hyperkalemia that are life threatThe most common
ening and require
immediate
therapy.
cause of
The most common
hyperkalemia in
cause of hyperkalemia
infants and children
in infants and children
is ‘‘pseudo hyperkaleis ‘‘pseudo
mia’’ from hemolysis
hyperkalemia’’
of the blood sample
from hemolysis of
when the sample is obtained from a heel stick
the blood sample
or a small bore intravewhen the sample is
nous
line.
When
obtained from
pseudo hyperkalemia
is suspected, the test
a heel stick or
to determine the serum
a small bore
potassium level should
intravenous line.
be repeated from
a free-flowing venous
sample before any treatment is administered. Otherwise, hyperkalemia is most commonly seen in patients
with end-stage renal disease or in those who
Journal of Pediatric Health Care
TABLE 2. Electrocardiographic manifestations for hypokalemia and hyperkalemia
Serum potassium
concentration
< 3.5 mEq/L; does not
correlate with specific
potassium levels
Hypokalemia
Serum potassium
concentration
Increased P wave amplitude
5.5-6.5 mEq/L
Prolonged PR interval, ST
segment depression
QT prolongation, reduction
in T wave amplitude
T wave inversion, U waves
6.5-7.5 mEq/L
7.0-8.0 mEq/L
> 8 mEq/L
Hyperkalemia
Tall, peaked, ‘‘tented’’ T waves, normal or decreased
QT, PR interval shortening
Widening of QRS complex, increased PR interval
Broad, low-amplitude P waves, QT prolongation,
ST elevation or depression
P waves disappear, marked widening of QRS + ‘‘sine
wave’’ pattern, high risk for ventricular fibrillation or
asystole
Note. Data from Taketomo, Hodding, & Kraus (2013) and Sood, Sood, & Richardson. (2007). Emergency management and commonly encountered outpatient scenarios in patients with hyperkalemia. Mayo Clinic Proceedings, 82(12), 1553-1561.
experience acute renal failure (Masilamani & Van der
Voort, 2012). The causes of hyperkalemia are summarized in Boxes 2 and 3. Identification of potential
causes of hyperkalemia will be beneficial when
determining optimal treatment.
Clinical manifestations of hyperkalemia include
weakness, confusion, and muscular or respiratory paralysis (Kleinman et al., 2010). Early electrocardiographic
(ECG) changes seen with an increase in the potassium
level include peaked T waves followed by a decrease
in R wave amplitude, widened QRS complex, and a
prolonged PR interval. This scenario may ultimately
progress to complete heart block with absent P waves
and finally a sine wave. Ventricular arrhythmias or
cardiac arrest may ensue if no effort is made to lower
the serum potassium level. Although the sequences of
ECG abnormalities correlate with the serum potassium
concentrations, the potassium levels at which specific
ECG abnormalities are seen vary widely from patient
to patient.
Treatment of hyperkalemia depends on the serum
potassium level, as well as the presence or absence of
symptoms and ECG changes. Table 2 includes a list of
ECG changes based on hypokalemia and hyperkalemia
serum concentrations. Treatment is recommended
when ECG changes are present or when serum potassium levels are greater than 6 to 6.5 mEq/L, regardless
of the ECG findings. The first step is to identify and remove all sources of oral or parenteral potassium intake
(oral potassium supplements and intravenous maintenance fluids or parenteral nutrition must be considered) and evaluate drugs that can increase the serum
potassium level (e.g., potassium-sparing diuretics,
angiotensin-converting enzyme inhibitors, and nonsteroidal antiinflammatory agents). A list of commonly
used medications that can increase serum potassium
is provided in Box 3.
The goals of hyperkalemia treatment are to antagonize the cardiac effects of potassium, reverse symptoms, and return the serum potassium level to normal
www.jpedhc.org
while avoiding overcorrection. Three principle
methods are used to treat hyperkalemia. First, calcium
is administered to counteract the effects of excess potassium on the heart. Second, medications can be
used to shift potassium from extracellular to intracellular fluid compartments. Third, exchange resins, diuretics, or dialysis are used to remove potassium from
the body (Farrington, 1991). Table 3 lists treatment options for hyperkalemia.
CALCIUM
Calcium increases the cellular threshold potential,
thereby restoring the normal difference between
the resting membrane potential and the firing threshold, which is elevated abnormally in persons with
hyperkalemia. This type of treatment is temporary
to antagonize the effects of hyperkalemia on cardiac
muscle and will not remove potassium from the body
(Schaefer & Wolford, 2005). Calcium should be administered intravenously to symptomatic patients or
those with ECG changes. In the presence of a lifethreatening arrhythmia, 20 mg/kg of calcium chloride
(with a maximum dose of 1 g) or 100 mg/kg of calcium gluconate (with a maximum dose of 1 g) may
be given intravenously over 2 to 5 minutes to reduce
the effects of potassium at the myocardial cell membrane (Taketomo, Hodding, & Kraus, 2013). The
dose may be repeated in 5 minutes; continuous monitoring of the ECG is mandatory. The cardiac response to an injection of calcium is seen within 5
minutes and may last for up to 1 hour (Farrington,
1991). Calcium must be administered with caution
to patients receiving digitalis glycosides because the
cardiac glycosides are synergistic with parenteral calcium salts and thus the combination of digitalis and
calcium may increase the risk of precipitating
hypokalemia-related arrhythmias (Taketomo et al.,
2013). Because the administration of calcium does
not lower serum potassium, other modes of treatment must be initiated.
November/December 2013
489
490
Volume 27 Number 6
TABLE 3. Treatment of hyperkalemia
Drug
Pediatric dose
(max: adult dose)
Adult
dose
Route
Administration
time
Onset
Length
of effect
Calcium
chloride 10%
Calcium
gluconate 10%
Sodium
bicarbonate
20 mg/kg/ dose
1-2 g
IV, IO
2-5 min
5 min
30-60 min
60-100 mg/kg/dose
1-2 g
IV, IO
2-5 min
5 min
30-60 min
1-2 mEq/kg/dose
50-100 mEq
IV, IO
2-5 min
Various
50% dextrose
102 ml/kg
50 ml
IV, IO
5 min
15-60 min
depending on
acid base status
of the patient
20 min
10% dextrose
5-10 ml/kg
250 ml
IV, IO
5 min
Regular insulin
0.2 units/kg
5-10 units
IV, IO
Kayexalate
1 g/kg
60 g
Albuterol
10-20 mg (use
concentrated
form, 5 mg/ml)
1 mg/kg
10-20 mg (use
concentrated
form, 5 mg/ml)
40 mg
Furosemide
Journal of Pediatric Health Care
Hemodialysis
Notes
Adverse effects
May repeat in 5 min
if necessary
May repeat in 5 min
if necessary
May repeat every
5-10 min
Burning at the infusion site
6 hr
Administer with insulin
20 min
6 hr
Administer with insulin
5 min
20 min
2-6 hr
Administer with glucose
Oral or rectal
N/A
4-6 hr
Effective but slow
Inhale by
nebulizer
10 min
Oral: 1-2 hr Rectal:
< 30 min
30 min
Hypoglycemia, hyperosmolarity,
volume overload
Hypoglycemia, hyperosmolarity,
volume overload
Hypoglycemia, hyperosmolarity,
volume overload
Nausea and vomiting
2 hr
IV
1-2 min
5-30 min
4 hr
N/A
N/A
N/A
N/A
Efficacy demonstrated in
patients with renal
insufficiency
Amount of potassium
excretion is unreliable
and does not correlate
to furosemide dose
Hypotension
Note. IO = interosseous; IV = intravenous; N/A = not applicable. Data from Taketomo, Hodding, & Kraus (2013).
Burning at the infusion site
Hypernatremia, metabolic alkalosis
Tachycardia, vasomotor flushing,
mild tremor
Volume depletion
Volume depletion
TREATMENT THAT SHIFTS POTASSIUM INTO
CELLS
Increasing the Serum pH of the Acidotic Patient
The most rapid treatment for hyperkalemia in an acidotic patient is hyperventilation. However, the decrease in serum potassium level seen with acute
increases in pH resulting from decreases in partial pressure of carbon dioxide (PCO2) may be less than that seen
with comparable improvements in pH obtained with
intravenously administered sodium bicarbonate
(NaHCO3; Lehnhardt & Kemper, 2011). Classically, it
has been taught that for every 0.1 increase in serum
pH, serum potassium will decrease by approximately
0.6 mEq/L. However, observed changes in serum potassium concentrations vary widely, depending, in part,
on the origin of the acid or base load. Hyperventilation,
or a decrease in the PCO2 (respiratory alkalosis), is associated with a decrease in serum potassium of only 0.1 to
0.3 mEq/L for each 0.1 pH unit change (Lehnhardt &
Kemper, 2011).
Sodium Bicarbonate
NaHCO3 is used because the alkaline systemic pH it
produces favors the shift of potassium intracellularly,
and the sodium load enhances distal tubular potassium secretion (Galla, 2000). Thus the administration
of sodium bicarbonate is most effective in a patient
who is acidotic and will have less of an effect on a nonacidotic hyperkalemic patient. In addition, NaHCO3 administration can cause an ‘‘overshoot’’ alkalosis in an
oliguric patient who is unable to excrete the administrated NaHCO3. The dose of NaHCO3 is 1 to 2 mEq/kg
injected intravenously over 1 to 5 minutes (with a maximum dose of 50 to 100 mEq; Taketomo et al., 2013).
This treatment may be repeated every 5 to 10 minutes
as needed to reverse ECG abnormalities (Farrington,
1991). Administration of NaHCO3 can have a rapid effect; however, it only causes a temporary redistribution of potassium into the intracellular space and
does not change total body potassium levels
(Masilamani & Van der Voort, 2012). Therefore additional therapy should be administered to remove serum potassium. Patients with coexisting respiratory
failure should not be given NaHCO3. Because patients
with respiratory failure cannot eliminate the increase
of CO2 production that results from NaHCO3 metabolism, respiratory acidosis will develop. For each 1
mEq of NaHCO3 that is administered, the patient receives 1 mEq of sodium. Therefore NaHCO3 should
be used with caution in patients with heart failure or
renal failure because of its sodium content, which
could exacerbate fluid retention.
Glucose Plus Insulin
Glucose plus insulin infusions shift potassium intracellularly. Insulin stimulates cellular uptake of glucose
with potassium following, thus lowering its serum conwww.jpedhc.org
centration (Palmer, 2010). However, if the patient is hyperglycemic, only the administration of insulin is
recommended to treat the hyperkalemia. Remember
that the effects of intravenously administered insulin
frequently extend several hours after the dextrose has
been consumed, which may result in delayed hypoglycemia. Glucose, 500 mg/kg (maximum dose 25 g), and
insulin, 0.2 units/kg (5 to 10 units), are administered
over a 5-minute period (Farrington, 1991; Taketomo
et al., 2013). The hypokalemic effect of this treatment
can be seen within 20 minutes, peaks between 30 and
60 minutes, and may last for up to 6 hours. A
continuous infusion of glucose and insulin may be
initiated after the initial glucose/insulin bolus (10
units of regular insulin in 500 ml dextrose 10%). This
is a ratio of 0.2 units of regular insulin per 1.0 g of
glucose (Parham, Mehdirad, Biermann, & Fredman,
2006). It is recommended that finger-stick tests for
blood glucose levels be checked hourly for at least 6
hours after insulin and dextrose have been administered.
b-Adrenergic Agonists
Albuterol and other b-adrenergic agents induce the intracellular movement of potassium via the stimulation
of the sodium/potassium–adenosine triphosphate
pump. Inhaled b2 agonists have a rapid onset of action.
The effect of b2 agonists is additive to that of insulin or
NaHCO3 administration, and they can be administered
concurrently.
The majority of published data concerning the efficacy of albuterol in persons with hyperkalemia has
been in patients with chronic renal failure. Intravenous administration of salbutamol at a dose of 5 mg/
kg over 15 minutes has demonstrated a predictable
decrease in serum potassium with a mean decrease
of 1.6 to 1.7 mEq/L after 2 hours (Kember, Harps,
Hellwege, & Mueller-Wiefel, 1996). Injectable salbutamol is not available in the United States; however,
nebulized albuterol has demonstrated efficacy
(Weisberg, 2008). Studies show that a nebulization of
10 mg of albuterol leads to a decline in serum
potassium of 0.6 mmol/kg and a nebulized dose of albuterol 20 mg demonstrates a decline in pharmacokinetics (about 1 mmol/L; Weisberg, 2008). Note that the
effective dose of albuterol for hyperkalemia is at least
four times higher than that typically used for bronchodilation. The clinical effect of high-dose albuterol is
apparent at 30 minutes and persists for at least 2 hours
(Weisberg, 2008). A single study demonstrated that the
administration of subcutaneous terbutaline (7 mg/kg)
reduces serum potassium in patients undergoing dialysis by an average of 1.3 mEq/L within 60 minutes
(Sowinski, Cronin, Mueller, & Kraus, 2005). Mild
tachycardia is the most common reported adverse effect of high-dose nebulized albuterol or terbutaline.
It is unlikely that patients who take nonselective
November/December 2013
491
b-blockers will have a hypokalemic effect from nebulized albuterol. Approximately 40% of patients who do
not take b-blockers seem to be resistant to the hypokalemic effect of albuterol. The mechanism for this resistance is currently unknown, and there is no basis for
predicting which patients will respond. Because of
this uncertainty, albuterol should never be used as
a single agent for the treatment of urgent hyperkalemia in patients with renal failure (Nissenson & Fine,
2005).
TREATMENT THAT REMOVES POTASSIUM
Exchange Resins
Sodium polystyrene sulfonate or Kayexalate mixed in
sorbitol is a cation-exchange resin that binds potassium
in the gastrointestinal tract and eliminates it from the
body. Each gram of resin will bind approximately 1
mEq of potassium and release 2 to 3 mEq of sodium.
It should be given at a dose of 1 g/kg orally or per rectum (maximum dose: 60 g) and repeated every 1 to 2
hours until the serum potassium level is lowered
(Taketomo et al., 2013). The onset of action of sodium
polystyrene sulfonate administered orally is at least 2
hours, and the maximal effect may take 6 hours
(Hollander-Rodriguez & Calvert, 2006).
Although the oral administration of Kayexalate is often considered unpalatable, it should not be mixed with
citrus juices or solutions that contain high concentrations of potassium because doing so will reduce the effectiveness of the resin. Because this resin exchanges
sodium for potassium, consideration should be given
to patients with congestive heart failure, elevated blood
pressure, or severe hepatic disease (Farrington, 1991).
Lastly, because of complications of hypernatremia
and necrotizing enterocolitis, Kayexalate use in neonates should be reserved for refractory cases
(Taketomo et al., 2013).
Diuretics
For patients who are not experiencing renal failure, the
administration of furosemide, a loop diuretic, will produce an increase in the renal excretion of potassium.
The onset of action of parenteral furosemide is within
5 minutes; the peak effect is observed within 30 minutes. The furosemide dose for children is 1 mg/kg/
dose (maximum 40 mg/dose; Taketomo et al., 2013).
The amount of potassium excreted is unreliable and
does not correlate with the diuretic dose; therefore,
the administration of diuretics should only be used as
an adjunct to other modes of therapy (Lehnhardt &
Kemper, 2011).
Renal Replacement Therapy
Renal replacement therapy is used when conservative
methods fail or for patients with life-threatening hyperkalemia. Hemodialysis (or continuous venovenous hemofiltration in hemodynamically unstable patients) is
492
Volume 27 Number 6
more effective than peritoneal dialysis and is the preferred method when hyperkalemia is the result of cell
breakdown (Weisberg, 2008). To be most effective,
peritoneal
dialysis
must be started early,
Hemodialysis is
because
potassium
much more
clearance rates by the
efficient at
peritoneal membrane
are limited by the limiremoving
tations on dialysate
potassium from the
flow rates inherent to
patient than all
the peritoneal dialysis
system. Hemodialysis
other treatment
is much more efficient
modalities
at removing potassium
from the patient than
all other treatment modalities. In patients with lifethreatening levels of hyperkalemia, hemodialysis
should be the treatment of choice (Lehnhardt &
Kemper, 2011).
Prevention of Recurrence
After hyperkalemia is treated, it is essential to determine
the cause and implement measures to prevent recurrence. In patients with renal dysfunction, management
for sustained hyperkalemia is to reduce the overall total
dietary potassium intake, which includes restriction in
the use of salt substitutes because they contain potassium chloride (KCl). In some studies it has been found
that fludrocortisone, an oral mineralocorticoid, is effective in lowering serum potassium levels in patients with
hyporenin hypoaldosteronism (Hollander-Rodriguez
& Calvert, 2006; Kim, Chung, Yoon, & Kim, 2007).
Fludrocortisone, an endogenous mineralocorticoid,
mimics the actions of aldosterone, and hence
hyperkalemia is reversed. The patient’s medication
regimen should be evaluated to see if it is causing
hyperkalemia, including over-the-counter medications
and herbal and dietary supplements. In patients with renal dysfunction, it may not be prudent to discontinue
therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker because they slow
progression of renal dysfunction. Instead, it may be in
the patient’s best interest to use oral Kayexalate daily,
which is effective in reducing the incidence of severe
hyperkalemia (Gennari, 2002).
Monitoring
In the acute management of hyperkalemia, the frequency of monitoring depends on the potassium level,
any underlying comorbidities experienced by the patient, and the physician’s preference. Once initial interventions have been made, the serum potassium level
should be rechecked within 1 to 2 hours to ensure the
effectiveness of the correction. Depending on the underlying cause of the hyperkalemia and the level
when the potassium is rechecked, the physician may
Journal of Pediatric Health Care
BOX 4. Causes of hypokalemia
Intracellular shifts of potassium
Metabolic alkalosis (respiratory and metabolic)
b-Adrenergic agonists: albuterol, insulin, theophylline,
caffeine, and epinephrine
Hyperthyroidism
Delirium tremens
Barium poisoning
Therapy of hyperglycemia
Increased losses of potassium
Sodium polystyrene sulfonate, corticosteroids, and
magnesium depletion
Renal replacement therapy
Hemodialysis
Continuous renal replacement therapy
Decreased intake/gastrointestinal losses
Diarrhea
Vomiting
Increased colostomy output
Nasogastric drainage
Inadequate potassium intake (< 40 mEq/L)
Eating disorders
Alcoholism
Urinary loss
Diuretics: loop and thiazide
Antimicrobials: amphotericin B, cisplatin, aminoglycoside—piperacillin, ticarcillin
Diabetic ketoacidosis
Osmotic dieresis (diabetic ketoacidosis, mannitol)
Hypomagnesemia
Cushing syndrome
Primary mineralocorticoid excess
Bartter syndrome or Gitelman syndrome
Data from Gennari (2002) and Linshaw (1987).
choose to decrease or increase the frequency of potassium checks (Elliott et al., 2010).
HYPOKALEMIA
Hypokalemia occurs when a serum potassium concentration is < 3.5 mEq/L, and it can become lifethreatening when the serum potassium concentration
falls below 2.5 mEq/L (Table 2). Hypokalemia can
result from intracellular shifts of potassium, increased
losses of potassium, or decreased ingestion or administration of potassium (Box 4). The main cause of
hypokalemia in pediatric patients is excessive gastrointestinal losses such as diarrhea or vomiting. Because serum potassium levels do not correlate with intracellular
potassium levels, hypokalemia does not reflect total
body potassium stores. Clear cases of potassium deficiency, defined by symptoms, signs, and a low potassium level, are rare in healthy persons (Kleinman
et al., 2010).
www.jpedhc.org
The clinical manifestations of hypokalemia involve
changes to muscle and cardiovascular function because
hypokalemia results in membrane hyperpolarization
and impairs muscle contraction. Mild hypokalemia (3
to 3.5 mEq/L) may not cause symptoms. Moderate hypokalemia, with serum potassium concentrations of
2.5 to 3 mEq/L, may cause muscular weakness, myalgia,
muscle cramps (as a result of disturbed function of the
skeletal muscles), and constipation (as a result of disturbed function of smooth muscles). With more severe
hypokalemia, flaccid paralysis and hyporeflexia may
result. Reports have been made of rhabdomyolysis occurring with profound hypokalemia with serum potassium levels less than 2 mEq/L. Respiratory depression
from severe impairment of skeletal muscle may occur
with severe potassium depletion (Schaefer & Wolford,
2005).
TREATMENT OF HYPOKALEMIA
Treatment depends on the serum level of potassium, as
well as the presence or absence of symptoms and ECG
changes (Table 2). Early ECG changes include ST segment depression, T wave flattening, and the presence
of U waves. Like hyperkalemia, the sequence of ECG
abnormalities correlates with serum conPatients with
centrations, but the
symptomatic
potassium levels at
hypokalemia
which specific ECG abnormalities are seen
should be treated
vary widely from pawith
tient to patient. The
pharmacologic
goals of therapy for hypokalemia
include
therapy, because
avoidance or resoluincreasing the
tion of symptoms and
intake of
return of the serum potassium concentration
potassium-rich
to normal (Gennari,
foods only is
1998).
unlikely to resolve
If potassium were
to be removed from
symptoms in
the diet, a minimum
potassiumkidney excretion of
depleted patients.
about 200 mg per
day would continue
to occur. The serum potassium level would decline
to 3.0 to 3.5 mEq/L in about 1 week. If the serum potassium was not supplemented, the patient would experience further depletion in serum potassium levels
and could ultimately experience death. A potassium
intake sufficient to support life can in general be
guaranteed by eating a variety of foods. Patients
with symptomatic hypokalemia should be treated
with pharmacologic therapy, because increasing the
intake of potassium-rich foods only is unlikely to resolve symptoms in potassium-depleted patients.
November/December 2013
493
TABLE 4. Oral potassium replacement products
Potassium chloride preparations
Tablets, controlled release/extended
release
Tablets, controlled release/extended
release
Tablets, extended release
Tablets, controlled release/extended
release
Tablets, effervescent
Capsules, controlled release
Capsules, controlled release
Liquid
Liquid
Powder packets
Powder packets
Potassium gluconate preparations
Caplet
Capsule
Tablets
Tablets, timed-release
Liquid
Liquid
Potassium bicarbonate
Tablets, effervescent
Potassium bicarbonate and potassium citrate
Tablets, effervescent
Tablets, effervescent
Tablets, effervescent
Potassium phosphate
Tablet (K-Phos original)
Powder packet (Neutral-Phos K)
Powder packet (Neutral-Phos)
Potassium citrate
Tablet, extended release
Tablet, extended release
Tablet, extended release
Potassium citrate and citric acid
Liquid
Powder packets
# mEq/mg potassium
Salt form (mg)/miscellaneous
information
8
600 KCl
10
750 KCl
15
20
1125 KCl
1500 mg KCl
25
8
10
20 mEq/15 ml
40 mEq/15 ml
20 mEq/packet
25 mEq/packet
Chloride and bicarbonate salts
600 mg KCl
750 mg KCl
1125 mg/15 ml
2250 mg/15 ml
1500 mg KCl
1875 mg KCl
99 mg potassium
99 mg potassium
99 mg potassium/
90 mg potassium
95 mg potassium
20 mEq/15 ml
20 mEq/15 ml
595 mg potassium gluconate
595 mg potassium gluconate
595 mg potassium gluconate/550 mg
potassium gluconate
As the gluconate salt
A mixture of gluconate and citrate salts
25
Orange flavor
10
20
25
Unflavored and cherry vanilla flavor
Unflavored and orange cream flavor
Unflavored, orange, lemon citrus and
cherry berry flavor AND sugar free;
orange flavor
3.7 mEq
14 mEq KCl
7 mEq KCl
114 mg potassium and 114 mg phosphate
per tablet
8 mmol phos
8 mmol phos, 7 mEq NaCl
5 mEq
10 mEq
15 mEq
540 mg potassium citrate
1080 mg potassium citrate
1620 mg potassium citrate
2 mEq/mL
30 mEq
2 mEq/mL NaHCO3
30 mEq NaHCO3
Note. KCl = potassium chloride; NaCl = sodium chloride; NaHCO3 = sodium bicarbonate. Data from Taketomo, Hodding, & Kraus (2013).
Dietary potassium is predominantly in the form of
potassium phosphate or potassium citrate, which results in the retention of only 40% as much potassium
as KCl (Sanguinetti & Jurkiewicz, 1992). Therefore
pharmacotherapy of symptomatic hypokalemia
should be with KCl.
In the presence of cardiac arrhythmias, extreme muscle weakness, or respiratory distress, KCl should be administered intravenously with cardiac monitoring. The
intravenous dose of KCl is 0.5 mEq/kg (maximum 20
mEq/dose) administered over 1 to 2 hours based on
the severity of the patient’s symptoms (Taketomo
et al., 2013). Once the serum potassium level is stabi-
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Volume 27 Number 6
lized, the oral route of administration is preferable
(Schaefer & Wolford, 2005).
Oral potassium supplements are available as chloride,
bicarbonate, citrate, gluconate, and phosphate salts. Potassium bicarbonate is preferred in patients with hypokalemia and metabolic acidosis because of their renal
tubular acidosis or diarrhea. Administration of potassium phosphate should be considered only in patients
with hypokalemia and hypophosphatemia, which might
occur in patients with proximal renal tubular acidosis associated with Fanconi syndrome and phosphate wasting. Use of potassium chloride is preferred in patients
with hypokalemia, hypochloremia, and metabolic
Journal of Pediatric Health Care
TABLE 5. Intravenous potassium replacement
products
Infusion, premixed
in water for injection
Central or peripheral
line recommended
10 mEq/50 mL
10 mEq/100 mL
20 mEq/50 mL
20 mEq/100 mL
30 mEq/100 mL
40 mEq/100 mL
Mixed by pharmacy
# 0.1 mEq/mL
> 0.1 mEq/mL with a maximum
of 0.4 mEq/mL
Central
Peripheral
Central
Central
Central
Central
Peripheral
Central
Note. Data from Taketomo, Hodding, & Kraus (2013).
alkalosis because of diuretic therapy or vomiting. Chloride depletion contributes to maintenance of the metabolic alkalosis by enhancing renal bicarbonate
reabsorption and may contribute to potassium wasting
as sodium is reabsorbed in exchange for secreted potassium rather than with chloride. Compared with potassium bicarbonate, KCL raises the serum potassium
concentration more quickly (Schaefer &Wolford,
2005). Chloride is primarily an extracellular anion that
does not enter cells to the same extent as bicarbonate,
thereby promoting maintenance of the administered potassium in the extracellular fluid (Sanguinetti &
Jurkiewicz, 1992). The single oral dose of KCl is 1 to
1.5 mEq/kg/dose (maximum 40 mEq/dose; Taketomo
et al., 2013). If potassium deficits are severe or ongoing,
scheduled potassium doses may be necessary (Gennari,
1998). Potassium salts available for potassium replacement are summarized in Tables 4 and 5.
Patients with hypokalemia may also have hypomagnesemia as a result of concurrent loss of magnesium
with diarrhea or diuretic therapy or medications such
as cisplatin, carboplatin, and amphotericin B, which
cause renal magnesium wasting. In addition, magnesium depletion may cause renal potassium wasting. Because the major site of potassium reabsorption occurs in
the ascending loop of Henle and reabsorption at this
site is driven by a magnesium-dependent, sodium–potassium–adenosine triphosphatase pump, cellular depletion of magnesium in these cells prevents
potassium reabsorption (Schaefer & Wolford, 2005).
Treating the hypokalemia without addressing the hypomagnesemia will be ineffective. The measurement of
serum magnesium should be considered in patients
with hypokalemia, and if hypomagnesemia is present,
it should be treated prior to the administration of potassium. The recommended initial treatment is intravenous magnesium sulfate, 50 mg/kg/dose (maximum
dose: 2 g) administered over 2 hours (Taketomo et al.,
2013). This dose can be repeated if the hypomagnesemia persists.
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Monitoring
The timing of a repeat serum potassium level depends
on the severity of the initial value, the patient’s symptoms, and the form of potassium administered to the patient. In a symptomatic patient who receives an
intravenous dose of KCl, the dose should be repeated
without measuring a serum value if the patient’s symptoms persist. If the symptoms resolve, the serum potassium level can be obtained 1 hour after completion of an
intravenous dose (Schaefer & Wolford, 2005). In clinical
situations in which an oral dose is administered based
on a low serum value, in the absence of clinical symptoms, the serum level can be repeated the next day.
After hypokalemia is treated, it is essential to determine the cause and implement measures to prevent recurrence. Patients who receive diuretics or other
medications that cause a depletion of serum potassium
(Box 4) may need to begin taking a scheduled oral supplement.
CONCLUSION
Derangements in potassium homeostasis affect the
body’s bioelectric process, including muscle contraction, nerve conduction, and myocardial electrical activity. Alterations in the potassium level, whether it be
hyperkalemia or hypokalemia, may cause serious
symptoms in the patient. Knowledge of the causes of
hypokalemia and hyperkalemia and the therapeutic interventions recommended for their treatment can be
lifesaving for the patient.
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