Nephron 2002;92(suppl 1):28–32
DOI: 10.1159/000065374
Therapeutic Approach to Hypokalemia
Gheun-Ho Kim a Jin Suk Han b
a Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, and b Department of
Internal Medicine, Seoul National University, Clinical Research Institute of Seoul National University Hospital,
Seoul, Korea
Key Words
Hypokalemia W Treatment W Potassium W Replacement
Abstract
For successful potassium replacement, one should con-
sider the optimal potassium preparation, route of admin-
istration, and the appropriate speed of administration. In
the absence of an independent factor causing transcellu-
lar potassium shifts, the plasma potassium concentra-
tion can be used as a rough index to estimate body
potassium stores. Oral KCl replacement therapy is pref-
erable if there are bowel sounds, except in the setting of
life-threatening abnormalities such as ventricular ar-
rhythmias, digitalis intoxication, or paralysis. In patients
with impaired renal function or those treated with intra-
venous potassium, the risk of hyperkalemia should be
monitored. Since potassium depletion rarely occurs as
an isolated phenomenon, associated fluid and electro-
lyte disorders should be corrected, and the causes of
potassium loss should be sought and eliminated to com-
plete the treatment of hypokalemia.
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Hypokalemia is one of the most common electrolyte
abnormalities encountered in clinical practice. More than
20% of hospitalized patients have hypokalemia, when
defined as a serum potassium level of less than 3.6 mmol/l
[1]. The treatment of hypokalemia should address re-
placement of the potassium deficit and interruption of
potassium-losing mechanisms or elimination of underly-
ing causes. This article reviews the general principles
applicable to the therapy of potassium depletion of most
causes.
Potassium Replacement
Potassium replacement is primarily indicated when
potassium has been lost, either in urine or stool. The other
indication is hypokalemic periodic paralysis. In general,
however, potassium is not usually given in the setting of
hypokalemia due to redistribution into the cells, because
the hypokalemia is transient and the administration of
too much potassium can lead to rebound hyperkalemia
when the process is corrected. If severe muscular manifes-
tation is present in hypokalemic periodic paralysis, it is
reasonable to give a modest quantity of potassium.
The major aim of treatment of potassium depletion is
to get the patient out of danger and to avoid certain seri-
Jin Suk Han, MD, PhD
Department of Internal Medicine
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Seoul National University College of Medicine
28, Yongun-dong, Chongno-gu, Seoul, 110–744 (South Korea)
Chinese University of Hong Kong
Tel. +82 2 760 2392, Fax +82 2 3673 2392, E-Mail jshan@snu.ac.kr
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ous consequences, such as rhabdomyolysis or life-threat-
ening ventricular ectopy. Uncorrected preoperative hypo-
kalemia (!3.5 mmol/l) may increase the likelihood of
developing perioperative arrhythmia and the need for car-
diopulmonary resuscitation [2]. On the other hand, one
must bear in mind that the entire potassium deficit is not
corrected immediately to avoid the potential risk of
hyperkalemia. Occasionally, incorrect therapy of hypo-
kalemia can lead to paradoxical worsening of the hypokal-
emia. Table 1 summarizes the general principles of potas-
sium replacement.
Estimation of the Potassium Deficit
The first and sometimes most difficult step in treating
potassium depletion is estimating the size of the deficit.
Because bedside total body potassium determinations are
not feasible for routine clinical use, one is left using the
plasma potassium concentration as a tool by which to esti-
mate body potassium stores [3].
In addition, the initial step in the treatment of hypokal-
emia must include the assessment of the physiologic
effects of the potassium deficit. There is a wide variation
in the degree to which a given reduction in the plasma
potassium concentration will produce symptoms. Thus,
monitoring of the electrocardiogram and muscle strength,
which reflect the functional consequences of potassium
depletion, is an essential part of the management of
patients with severe hypokalemia [4].
If the factors that disturb the relationship between
intracellular and extracellular potassium are excluded, the
magnitude of the deficit in body stores of potassium cor-
relates with the degree of hypokalemia [5]. On average,
serum potassium decreases by 0.3 mmol/l for each 100-
mmol reduction in total body stores, but the response is
extremely variable.
Because potassium repletion is rarely an urgent under-
taking, one should always err on the low end of this esti-
mate to avoid inducing hyperkalemia. A portion of ad-
ministered potassium is always excreted, even in the pres-
ence of serious potassium depletion. Thus, supplemental
potassium is best administered in a moderate dose by
mouth over a period of days to weeks to correct deficits
fully [6, 7].
Selection of the Appropriate Preparation
A variety of potassium salts are available for oral and
intravenous use, including the chloride, bicarbonate, and
phosphate salts [6]. The selection of the type of potassium
salt depends on the anion lost together with potassium.
The chloride salt of potassium is most effective in raising
Therapeutic Approach to Hypokalemia
Table 1. Principles of potassium replacement
Potassium deficit
Assessment of the physiologic effects: electrocardiography,
muscle strength
Degree of plasma potassium level
Preparation of potassium salts
Potassium chloride: most effective, especially for Cl-depleted
metabolic alkalosis
Potassium bicarbonate (citrate, acetate, or gluconate): effective in
patients with mild degree of hypokalemia and metabolic acidosis
Potassium phosphate: useful to replace phosphate losses
Route of administration
Oral: preferred in general, if bowel sounds
Intravenous (concentration ^40–60 mmol/l): necessary either when
the patient cannot take oral medicines or when the potassium
deficit is very severe and is acutely causing cardiac arrhythmias,
quadriplegia, respiratory failure, or rhabdomyolysis
Rate of administration
Oral: 60–80 mmol/day initially, 100–150 mmol/day as necessary
Intravenous*:
Usual rate ^10–20 mmol/h
Emergency: 5–10 mmol over 15–20 min
* See text for details.
the serum potassium concentration, especially when the
hypokalemia is accompanied by chloride loss. In addi-
tion, the chloride salt of potassium provides the anion
necessary for correction of the alkalosis in the setting of
chloride depletion metabolic alkalosis.
Potassium bicarbonate is the preferred potassium salt
in certain patients with mild degrees of hypokalemia and
metabolic acidosis. For example, patients with renal tubu-
lar acidosis tend to waste potassium in the urine and
become potassium-depleted. In this setting, potassium in
combination with bicarbonate or a bicarbonate precursor
such as citrate, acetate, or gluconate is appropriate to cor-
rect both the potassium depletion and the acidemia. If
phosphate depletion accompanies a potassium deficit, as
for example with diabetic ketoacidosis, potassium phos-
phate therapy is rational.
Potassium chloride can be given orally in crystalline
form (salt substitutes), as a liquid, or in a slow-release tab-
let or capsule [4]. Slow-release preparations are generally
better tolerated than the poorly palatable potassium chlo-
ride solutions. However, these tablets or capsules can in
rare cases lead to ulcerative or stenotic lesions in the gas-
trointestinal tract as a result of the local accumulation of
high concentrations of potassium ion [8]. Salt substitute
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(which contains between 50 and 65 mmol per level tea-
spoon) may be the ideal form of oral therapy, being safe,
well tolerated, and much cheaper than the other prepara-
tions [9].
In comparison, the traditional therapy of treating
chronic hypokalemia with potassium-rich foods such as
orange juice or bananas is less desirable. These foods con-
tain phosphate and citrate rather than chloride and are
therefore less likely to correct the hypokalemia and meta-
bolic alkalosis [10].
Selection of Appropriate Route of Administration
Potassium can be repleted either orally or intrave-
nously. If the patient can take medicines orally, oral KCl
replacement is the preferred method. Intravenous potas-
sium replacement is necessary either when the patient
cannot take oral medicines or when the potassium deficit
is very severe and is acutely causing cardiac arrhythmias,
quadriplegia, respiratory failure, or rhabdomyolysis.
The standard intravenous KCl solution contains
2 mmol each of K+ and Cl – per ml. In most circum-
stances, 20–40 mmol of K+ (10–20 ml) is added to each
liter of intravenous solution. The vehicle solution should
be chosen carefully. Addition of a small concentration of
KCl, e.g. 20 mmol/l, to a dextrose solution may lower the
serum potassium concentration because insulin release is
stimulated, causing potassium translocation into cells
[11]. Although normal subjects can tolerate this decrease
in the plasma potassium concentration, arrhythmia may
be precipitated in patients who are hypokalemic or tak-
ing digitalis. Consequently, potassium supplementation
should be given in a non-dextrose-containing solution,
usually in a concentration of 40 mmol/l. In general, no
more than 60 mmol/l should be given through a peripher-
al vein, since higher concentrations of potassium are very
irritating, resulting in pain and sclerosis of the vein.
Selection of Appropriate Rate of Administration
The amount of potassium given is based on an esti-
mate of the degree of depletion and on the symptomatolo-
gy of the patient. The majority of patients have mild to
moderate hypokalemia, with the plasma potassium con-
centration ranging between 3.0 and 3.5 mmol/l. This
degree of potassium depletion is usually well tolerated in
the absence of digitalis therapy or severe hepatic disease.
Treatment is not urgent in this setting and must be
directed toward both repair of the potassium deficit and
prevention of further potassium loss by correcting the
underlying disorder. These patients can usually be treated
with oral KCl at an initial dose of 60–80 mmol/day. How-
30 Nephron 2002;92(suppl 1):28–32
ever, larger amounts (100–150 mmol/day) will be re-
quired if there is continued potassium loss. In the occa-
sional patient with severe symptoms or marked hypokal-
emia with electrocardiograhic changes, potassium must
be given more rapidly. This is more easily done orally, as
the plasma potassium concentration will acutely rise by as
much as 1.0–1.5 mmol/l after 40–60 mmol and by 2.5–3.5
mmol/l after 135–160 mmol [4]. These maximum effects,
however, are transient, since most of the administered
potassium will enter the cells to repair the cell deficit [12].
As a result, the plasma potassium concentration must be
carefully monitored and more potassium given as neces-
sary.
It is usually safe to give potassium intravenously if the
rate does not exceed 10–20 mmol/h. If rapid (110 mmol/
h) potassium administration is given intravenously, car-
diac monitoring in an intensive care unit is advisable.
One study found that 20 mmol/h of KCl causes the serum
potassium to increase by an average of 0.25 mmol/h [13].
Conditions requiring emergent therapy are rare. One
generally accepted indication for emergent therapy is a
patient with severe hypokalemia preparing to undergo
emergent surgery, particularly patients with known coro-
nary artery disease or who are taking digitalis. A second
generally accepted indication for emergent therapy is the
patient with an acute myocardial infarction and signifi-
cant ventricular ectopy. In such cases, administration of
5–10 mmol of KCl over 15–20 min, repeated as needed,
may be used to increase serum potassium level above
3.0 mmol/l [14]. As much as 40 to 100 mmol/h has been
given to patients with paralysis of respiratory muscles or
life-threatening ventricular arrhythmias [15, 16]. In those
cases, solutions containing as much as 200 mmol of K+
per liter have been used [13]. These solutions are best tol-
erated if given into a central vein, but the local increase in
the potassium concentration might, in some cases, have
deleterious effects on cardiac conduction.
It must be emphasized that the rapid administration of
potassium is potentially dangerous even in severely hypo-
kalemic patients and should be used only in life-threaten-
ing situations. A rate in excess of 80 mmol/h can result in
the electrocardiographic changes of hyperkalemia or com-
plete heart block [4]. Thus measurement of serum potas-
sium at very frequent intervals and continuous monitor-
ing of the electrocardiogram are essential in this setting.
In addition, the concentrated solutions should contain
only a limited amount of potassium per container to
avoid the accidental administration of very large quanti-
ties of potassium.
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 Correction of Associated Fluid and Electrolyte
Disorders
Potassium depletion rarely occurs as an isolated phe-
nomenon: nearly all disorders characterized by potassium
loss are accompanied by loss of other components of body
fluids, including sodium, chloride, water, bicarbonate, or
acid. Therefore, correction of associated disturbances in
volume, acid-base equilibrium, and particularly in mag-
nesium metabolism is an essential feature of the treat-
ment of potassium depletion. In some cases, the replace-
ment of potassium is less critical than treatment of the
associated disturbances. In most instances, correction of
effective arterial blood volume contraction takes prece-
dence [17]. For example, in the hypotensive patient with
massive diarrhea, hypokalemia, and metabolic acidosis,
rapid volume expansion takes precedence over correction
of either the potassium depletion or the metabolic aci-
dosis.
Metabolic alkalosis is the most common acid-base
abnormality accompanying hypokalemia and results from
the effects of hypokalemia on several components of net
acid excretion. The most direct effects include stimula-
tion of proximal tubule bicarbonate reabsorption and
ammoniagenesis [18, 19], collecting duct proton secre-
tion, possibly via stimulation of H-K-ATPase [20], and
decreasing urinary citrate excretion. Besides, Na-K-
ATPase mediates NH+4 uptake, providing an important
source of H+ for net acid secretion and for the titration of
luminal buffers in the terminal inner medullary collecting
duct [21]. This pathway contributes to the increase in
NH+4 excretion and metabolic alkalosis observed during
hypokalemia [22].
Hypomagnesemia can lead to renal potassium wasting
and refractoriness to potassium replacement. Correction
of the hypokalemia does not usually occur until the
hypomagnesemia is corrected [23]. Patients with di-
uretic-induced hypokalemia or unexplained hypokalemia
should be tested for hypomagnesemia, and replacement
therapy should be begun if magnesium depletion is docu-
mented. If potassium depletion is caused by magnesium
deficiency, the hypokalemia will reverse with repair of
the magnesium depletion as long as sufficient potas-
sium is available for retention. The coexistence of other
electrolyte abnormalities, particularly hypophosphate-
mia, should be also sought.
Therapeutic Approach to Hypokalemia
Elimination or Relief of the Cause of Potassium
Loss
Frequently, eliminating the cause of potassium loss is
sufficient in itself to permit dietary potassium supplies to
repair the potassium deficit [17]. In the patient with a
moderate degree of potassium depletion secondary to
diarrhea, for example, no special measures need to be
employed to repair the potassium deficit once diarrhea
has been brought under control, because potassium will
be retained from the normal large dietary potassium
intake (ranging between 40 and 120 mmol/day), and the
potassium deficit will disappear.
Spontaneous recovery from hypokalemia also follows
removal of tumors that overproduce adrenal steroids.
Such ‘spontaneous’ recovery may not occur in potassium
depletion associated with metabolic alkalosis, however.
Abundant evidence indicates that alkalotic patients, if
maintained on a low-chloride diet, will remain alkalotic,
potassium-depleted, and hypokalemic indefinitely, de-
spite the usual large dietary potassium intake [17]. All
ingested potassium in such patients is excreted in the
urine as a result of bicarbonaturia. Attempt to correct
potassium depletion in these patients must be with KCl.
Otherwise, the accompanying chloride deficiency would
maintain hypokalemic metabolic alkalosis.
Simple supplementation of potassium may be only
partially effective in conditions other than dietary defi-
ciency. Interruption or attenuation of kaliuretic mecha-
nisms needs to be addressed in the context of their etiolo-
gy [24]. In primary aldosteronism, for example, potas-
sium replacement is of minor benefit, and a K+-sparing
diuretic is required to maintain a normal plasma potas-
sium concentration. The transtubular potassium gradient
(TTKG) is a useful test to estimate aldosterone action in
distal nephron [25–27]. In some conditions such as Bart-
ter’s syndrome, additive treatment modalities need to be
used (e.g. potassium supplementation, indomethacin,
converting enzyme inhibitors) and even then success is
limited.
Prevention of Hypokalemia
Prevention of potassium depletion is possible in pa-
tients receiving diuretics and in those undergoing gastric
drainage. Because profound potassium depletion in these
settings is almost exclusively the result of alkalosis, potas-
sium depletion can be avoided by measures designed to
prevent metabolic alkalosis. Thus, particular attention
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must be paid in these patients to providing a sufficient
supply of chloride to ensure that a chloride deficit does
not develop. Usually, chloride is given in the form of
potassium chloride.
Patients with diuretic-induced hypokalemia should be
re-evaluated to reconsider the need for diuretics. If con-
tinual use is required, assessment of sodium intake should
be performed. Excessive sodium intake may accentuate
diuretic-induced hypokalemia [28]. The potassium defi-
ciency and alkalosis that accompany diuretic therapy in
the edematous patient can also be prevented by the use of
a potassium-sparing diuretic such as amiloride, triamter-
ene, or spironolactone. If indicated for other reasons,
beta-blockers or angiotensin-converting enzyme inhibi-
tors can assist in maintaining potassium level. In patients
undergoing gastric drainage, both alkalosis and potassium
deficiency can be prevented by administration of H2
receptor blocker or proton pump inhibitor. Raising gastric
fluid pH to 3 or 4 obviates significant acid loss and may
prevent the development of alkalosis and potassium de-
pletion [17].

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