Treatment and prevention of hyperkalemia in adults

Author: David B Mount, MD

Section Editor: Richard H Sterns, MD
Deputy Editor: John P Forman, MD, MSc

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jun 2018. | This topic last updated: Dec 18, 2017.

INTRODUCTION — Hyperkalemia is a common clinical problem that is most often a result

of impaired urinary potassium excretion due to acute or chronic kidney disease (CKD)
and/or disorders or drugs that inhibit the renin-angiotensin-aldosterone system (RAAS).
Therapy for hyperkalemia due to potassium retention is ultimately aimed at inducing
potassium loss [1,2].

In some cases, the primary problem is movement of potassium out of the cells, even
though the total body potassium may be reduced. Redistributive hyperkalemia most
commonly occurs in uncontrolled hyperglycemia (eg, diabetic ketoacidosis or hyperosmolar
hyperglycemic state). In these disorders, hyperosmolality and insulin deficiency are
primarily responsible for the transcellular shift of potassium from the cells into the
extracellular fluid, which can be reversed by the administration of fluids and insulin. Many of
these patients have a significant deficit in whole body potassium and must be monitored
carefully for the development of hypokalemia during therapy. (See "Diabetic ketoacidosis
and hyperosmolar hyperglycemic state in adults: Treatment", section on 'Potassium
replacement'.)

The treatment and prevention of hyperkalemia will be reviewed here. The causes, diagnosis,
and clinical manifestations of hyperkalemia are discussed separately. (See "Causes and
evaluation of hyperkalemia in adults" and "Clinical manifestations of hyperkalemia in
adults".)

DETERMINING THE URGENCY OF THERAPY — The urgency of treatment of hyperkalemia

varies with the presence or absence of the symptoms and signs associated with
hyperkalemia, the severity of the potassium elevation, and the cause of hyperkalemia.

Our approach to therapeutic urgency is as follows (algorithm 1):

● Hyperkalemic emergency − In general, the following patients should be considered to

have a hyperkalemic emergency and should therefore be treated with rapidly acting
therapies (ie, intravenous calcium, insulin, and glucose) in addition to therapies that
remove potassium from the body (such as hemodialysis, gastrointestinal potassium
binders, or diuretics):

• Patients who have clinical signs or symptoms of hyperkalemia. The most serious
manifestations of hyperkalemia are muscle weakness or paralysis, cardiac
conduction abnormalities, and cardiac arrhythmias, including sinus bradycardia,
sinus arrest, slow idioventricular rhythms, ventricular tachycardia, ventricular
fibrillation, and asystole. These manifestations usually occur when the serum
potassium concentration is ≥7 mEq/L with chronic hyperkalemia, or possibly at
lower levels in patients with an acute rise in serum potassium and/or underlying
cardiac conduction disease. (See "Clinical manifestations of hyperkalemia in
adults".)

There are several characteristic electrocardiogram (ECG) abnormalities associated

with hyperkalemia (figure 1). A tall peaked T wave with a shortened QT interval is
the earliest change (waveform 1), followed by progressive lengthening of the PR
interval and QRS duration (waveform 2). The P wave may disappear, and ultimately,
the QRS widens further to a sine wave. Ventricular standstill with a flat line on the
ECG ensues with complete absence of electrical activity. The progression and
severity of ECG changes do not correlate well with the serum potassium
concentration. Conduction abnormalities, such as bundle branch blocks and
arrhythmias (sinus bradycardia, sinus arrest, slow idioventricular rhythms,
ventricular tachycardia, ventricular fibrillation, and asystole) may also occur in
hyperkalemia. (See "Clinical manifestations of hyperkalemia in adults", section on
'ECG changes'.)

• Patients with severe hyperkalemia (serum potassium greater than 6.5 mEq/L),
especially if there is concurrent tissue breakdown or gastrointestinal bleeding,
even if there are no clinical signs or symptoms.

• Some patients with moderate hyperkalemia (>5.5 mEq/L) who have significant
renal impairment and marked, ongoing tissue breakdown (eg, rhabdomyolysis or
crush injury, tumor lysis syndrome), ongoing potassium absorption (eg, from
substantial gastrointestinal bleeding), or a significant non-anion gap metabolic
acidosis or respiratory acidosis. Tissue breakdown can release large amounts of
potassium from cells, which can lead to rapid and substantial elevations in serum
potassium. Potassium absorption from the blood in the gastrointestinal tract or
soft tissues can produce similar rapid increases in the serum potassium. Patients
with a non-gap acidosis or respiratory acidosis may develop severe hyperkalemia
quickly if the acidosis worsens, or if they develop an additional superimposed
metabolic or respiratory acidosis, particularly when renal function is impaired. (See
"Crush-related acute kidney injury" and "Tumor lysis syndrome: Definition,
 pathogenesis, clinical manifestations, etiology and risk factors" and "Prevention
and treatment of heme pigment-induced acute kidney injury" and "Potassium
balance in acid-base disorders".)

● Patients needing prompt therapy − Some patients without a hyperkalemic emergency

should, nonetheless, have their potassium lowered promptly (ie, within 6 to 12 hours).
Such patients include hemodialysis patients who present outside of regular dialysis
hours, patients with marginal renal function and/or marginal urine output, or
hyperkalemic patients who need to be optimized for surgery. Measures such as
isotonic bicarbonate infusion, intravenous 5 percent dextrose in water infusion
overnight (to stimulate insulin in a fasting patient), or hemodialysis may be appropriate
in these settings. Additional measures can include oral potassium binders or kaliuresis
induced by intravenous saline with diuretic therapy.

● Patients who can have the potassium lowered slowly − Most patients with
hyperkalemia have chronic, mild (≤5.5 mEq/L) or moderate (5.5 to 6.5 mEq/L)
elevations in serum potassium due to chronic kidney disease (CKD) or the use of
medications that inhibit the renin-angiotensin-aldosterone system ([RAAS] or both).
Such patients do not require urgent lowering of the serum potassium and can often be
treated with dietary modification, use of diuretics (if otherwise appropriate), treatment
of chronic metabolic acidosis, or reversal of factors that can cause hyperkalemia (eg,
nonsteroidal anti-inflammatory drugs, hypovolemia). In some instances, drugs that
inhibit the RAAS are reduced or discontinued, and drugs that remove potassium by
gastrointestinal cation exchange are prescribed for chronic use.

PATIENTS WITH A HYPERKALEMIC EMERGENCY — Identifying patients who have a

hyperkalemic emergency is presented above (algorithm 1). (See 'Determining the urgency
of therapy' above.)

Treatment approach to hyperkalemic emergencies — Patients with a hyperkalemic

emergency should receive (table 1):

● Intravenous calcium to antagonize the membrane actions of hyperkalemia (see

'Calcium' below)

● Intravenous insulin (typically given with intravenous glucose) to drive extracellular

potassium into cells (see 'Insulin with glucose' below)

● Therapy to rapidly remove excess potassium from the body (ie, loop or thiazide
diuretics if renal function is not severely impaired, a gastrointestinal cation exchanger,
and/or dialysis [preferably hemodialysis] if renal function is severely impaired) (see
'Remove potassium from the body' below)
 ● Treatment of reversible causes of hyperkalemia, such as correcting hypovolemia and
discontinuing drugs that increase the serum potassium (eg, nonsteroidal anti-
inflammatory drugs, inhibitors of the renin-angiotensin-aldosterone system) (table 2
and table 3) (see "Causes and evaluation of hyperkalemia in adults" and 'Drug-induced
hyperkalemia' below)

Intravenous calcium and insulin are rapidly acting treatments that provide time for the
initiation of therapies that remove the excess potassium from the body (table 4).

Monitoring — Continuous cardiac monitoring and serial electrocardiograms (ECGs) are

warranted in patients with hyperkalemia who require rapidly acting therapies. The serum
potassium should be measured at one to two hours after the initiation of treatment. The
timing of further measurements is determined by the serum potassium concentration and
the response to therapy. Patients who receive insulin, with or without dextrose, should
undergo hourly glucose measurements for up to six hours in order to monitor for
hypoglycemia.

Administer rapidly acting therapies

Calcium — Calcium directly antagonizes the membrane actions of hyperkalemia [3],

while hypocalcemia increases the cardiotoxicity of hyperkalemia [4]. As discussed
elsewhere, hyperkalemia-induced depolarization of the resting membrane potential leads to
inactivation of sodium channels and decreased membrane excitability. (See "Clinical
manifestations of hyperkalemia in adults", section on 'Pathogenesis'.)

The effect of intravenous calcium administration begins within minutes but is relatively
short lived (30 to 60 minutes). As a result, calcium should not be administered as
monotherapy for hyperkalemia but should rather be combined with therapies that drive
extracellular potassium into cells. Administration of calcium can be repeated every 30 to 60
minutes if the hyperkalemic emergency persists and the serum calcium does not become
elevated. (See 'Insulin with glucose' below.)

Calcium can be given as either calcium gluconate or calcium chloride. Calcium chloride
contains three times the concentration of elemental calcium compared with calcium
gluconate (13.6 versus 4.6 mEq in 10 mL of a 10 percent solution). However, calcium
gluconate is generally preferred because calcium chloride may cause local irritation at the
injection site.

The usual dose of calcium gluconate is 1000 mg (10 mL of a 10 percent solution) infused
over two to three minutes, with constant cardiac monitoring. The usual dose of calcium
chloride is 500 to 1000 mg (5 to 10 mL of a 10 percent solution), also infused over two to
three minutes, with constant cardiac monitoring. The dose of either formulation can be
repeated after five minutes if the ECG changes persist or recur.
Concentrated calcium infusions (particularly calcium chloride) are irritating to veins, and
extravasation can cause tissue necrosis. As a result, a central or deep vein is preferred for
administration of calcium chloride. Calcium gluconate can be given peripherally, ideally
through a small needle or catheter in a large vein. Calcium should not be given in
bicarbonate-containing solutions, which can lead to the precipitation of calcium carbonate.

When hyperkalemia occurs in patients treated with digitalis, calcium should be

administered for the same indications as in patients not treated with digitalis (eg, widening
of the QRS complex or loss of P waves) even though hypercalcemia potentiates the
cardiotoxic effects of digitalis. In such patients, a dilute solution can be administered
slowly, infusing 10 mL of 10 percent calcium gluconate in 100 mL of 5 percent dextrose in
water over 20 to 30 minutes, to avoid acute hypercalcemia [1]. In patients with hyperkalemia
due to digitalis toxicity, the administration of digoxin-specific antibody fragments is the
preferred therapy. (See "Digitalis (cardiac glycoside) poisoning", section on 'Electrolyte
abnormalities'.)

Insulin with glucose — Insulin administration lowers the serum potassium concentration

by driving potassium into the cells, primarily by enhancing the activity of the Na-K-ATPase
pump in skeletal muscle [1,5]. Glucose is usually given with insulin to prevent the
development of hypoglycemia. However, insulin should be given alone if the serum glucose
is ≥250 mg/dL (13.9 mmol/L) [6]. The serum glucose should be measured every hour for
five to six hours after the administration of insulin, given the risk of hypoglycemia.

One commonly used regimen for administering insulin and glucose is 10 to 20 units of
regular insulin in 500 mL of 10 percent dextrose, given intravenously over 60 minutes.
Another regimen consists of a bolus injection of 10 units of regular insulin, followed
immediately by 50 mL of 50 percent dextrose (25 g of glucose). This regimen may provide a
greater early reduction in serum potassium since the potassium-lowering effect is greater
at the higher insulin concentrations attained with bolus therapy. However, hypoglycemia
occurs in up to 75 percent of patients treated with the bolus regimen, typically
approximately one hour after the infusion [7]. To avoid this complication, we recommend
subsequent infusion of 10 percent dextrose at 50 to 75 mL/hour and close monitoring of
blood glucose levels every hour for five to six hours.

The administration of glucose without insulin is not recommended, since the release of
endogenous insulin can be variable and the attained insulin levels are generally lower with a
glucose infusion alone [8]. Furthermore, in susceptible patients (primarily diabetic patients
with hyporeninemic hypoaldosteronism), hypertonic glucose in the absence of insulin may
acutely increase the serum potassium concentration by raising the plasma osmolality,
which promotes water and potassium movement out of the cells [9-11].
The effect of insulin begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts for
four to six hours [7,12-14]. In almost all patients, the serum potassium concentration drops
by 0.5 to 1.2 mEq/L [14-17]. In particular, although patients with renal failure are resistant to
the glucose-lowering effect of insulin, they are not resistant to the hypokalemic effect,
because Na-K-ATPase activity is still enhanced [18,19]. (See "Carbohydrate and insulin
metabolism in chronic kidney disease".)

Repeated dosing — Removal of excess potassium from the body (eg, with

hemodialysis or a gastrointestinal cation exchanger) is sometimes not feasible or must be
delayed. Such patients can be treated with either a continuous infusion of insulin and
glucose or bolus infusions of insulin with glucose, repeated every two to four hours, with
serial monitoring of blood glucose levels.

Remove potassium from the body — The effective modalities described above only
transiently lower the serum potassium concentration. Thus, additional therapy is typically
required to remove excess potassium from the body, except in patients who have reversible
hyperkalemia resulting from increased potassium release from cells due, for example, to
metabolic acidosis or insulin deficiency and hyperglycemia. (See "Causes and evaluation of
hyperkalemia in adults", section on 'Increased potassium release from cells'.)

The three available modalities for potassium removal are diuretics, gastrointestinal cation
exchangers (eg, patiromer, sodium polystyrene sulfonate [SPS], and zirconium cyclosilicate
[ZS-9]), and dialysis. In patients with a hyperkalemic emergency, diuretics should not be the
only method used to remove potassium from the body.

Loop diuretics in patients without severe renal impairment — Loop diuretics increase

potassium loss in the urine in patients with normal or mild to moderately impaired renal
function, particularly when combined with saline hydration to maintain distal sodium
delivery and flow. However, patients with persistent hyperkalemia typically have impaired
renal potassium secretion, and there are no data demonstrating a clinically important short-
term kaliuretic response to diuretic therapy. Thus, diuretics should not be used as the only
means to remove potassium from the body in patients with a hyperkalemic emergency.

In hypervolemic patients with preserved renal function (eg, patients with heart failure), we
administer 40 mg of intravenous furosemide every 12 hours or a continuous furosemide
infusion. In euvolemic or hypovolemic patients with preserved renal function, we administer
isotonic saline at a rate that is appropriate to replete hypovolemia and maintain euvolemia,
followed by 40 mg of intravenous furosemide every 12 hours or a continuous furosemide
infusion.

If renal function is not preserved, we use a combination of an intravenous isotonic

bicarbonate or isotonic saline infusion plus intravenous furosemide at doses that are
appropriate for the patient's renal function. (See "Loop diuretics: Maximum effective dose
and major side effects".)

Dialysis and gastrointestinal cation exchangers — Gastrointestinal cation exchangers,

including patiromer, ZS-9, and SPS, bind potassium in the gastrointestinal tract in exchange
for other cations, such as sodium or calcium. Such therapies can be used to treat
hyperkalemia in patients with or without severe renal impairment.

Hemodialysis in patients with severe renal dysfunction — Hemodialysis is indicated

in hyperkalemic patients with severe renal impairment, and is preferable to cation
exchangers if the patient has functioning vascular access for dialysis and if the procedure
can be performed without delay. However, if hemodialysis cannot be performed promptly
(eg, within six hours), we administer gastrointestinal cation exchange therapy (preferably
not SPS) and then perform hemodialysis as soon as possible.

Patiromer or ZS-9 — When using a cation exchanger in patients with a hyperkalemic

emergency, we use patiromer if it is available (8.4 g, repeated daily as needed), rather than
SPS. ZS-9 is not yet approved for use in hyperkalemic patients. Although both patiromer
and ZS-9 (which is not yet available) may have a role in acutely reducing serum potassium
in patients with hyperkalemic emergency, this has yet to be established. Our approach is
based upon short-term effects of this drug in a separate patient population (ie, those
treated for chronic moderate hyperkalemia). (See 'Patiromer' below.)

SPS in rare settings — SPS may also lower the serum potassium in patients
presenting with a hyperkalemic emergency [20,21]. In one retrospective uncontrolled study,
for example, 501 patients with acute hyperkalemia were treated with 15 to 60 g of SPS;
serum potassium decreased by a mean of 0.93 mEq/L by the time the serum potassium
was measured again (typically within 24 hours) [21]. However, adverse effects were
common and two patients developed bowel necrosis, a well-described complication of SPS
[22-26].

SPS with or without sorbitol should not be given to the following patients because they may
be at high risk for intestinal necrosis [23,24,27,28]:

● Postoperative patients

● Patients with an ileus or who are receiving opiates

● Patients with a large or small bowel obstruction

● Patients with underlying bowel disease, eg, ulcerative colitis or Clostridium difficile
colitis
Even if restoration of renal function or dialysis is not possible or immediately available, SPS
should not be given in these high-risk settings; if other cation exchangers are not available,
such patients can be managed with repeated doses of insulin and glucose (or continuous
infusions) until dialysis can be performed. Other measures include the administration of
isotonic bicarbonate and high-dose diuretics (if there is residual urine output). (See 'Sodium
bicarbonate' below.)

Thus, we suggest that SPS be used (in conjunction with the rapidly acting transient
therapies mentioned above) only in a patient who meets all of the following criteria:

● Patient has potentially life-threatening hyperkalemia

● Dialysis is not readily available

● Newer cation exchangers (eg, patiromer) are not available

● Other therapies to remove potassium (eg, diuretics, rapid restoration of kidney

function) have failed or are not possible

In addition, if SPS is used, other orally administered drugs should be taken at least three
hours before or three hours after the dose of SPS [29]. SPS binds to and prevents the
absorption of many common medications.

The majority of intestinal necrosis cases associated with SPS occurred when the resin was
administered with sorbitol [22-26]. In addition, intestinal necrosis was induced in a rat
model by sorbitol alone or by sorbitol mixed with SPS but not with SPS alone [25]. Thus, it
was presumed that sorbitol was required for the intestinal injury. As a result, the US Food
and Drug Association (FDA) issued a recommendation in September 2009 that SPS should
no longer be administered in sorbitol [22]. Despite this, many hospitals and pharmacies
only stock sodium polystyrene sulfonate premixed in sorbitol. SPS alone is not always
available and, when available, comes as a powder that must be reconstituted.

However, the association of SPS in sorbitol with intestinal necrosis may be coincidental
since sorbitol is so widely used in conjunction with SPS. In addition, contemporary studies
have found that SPS alone can cause intestinal necrosis in rats and have suggested that the
previously noted toxicity of sorbitol alone in rats may have resulted from the hypertonic
solution in which it was suspended [30].

Multiple clinical cases of intestinal necrosis with SPS and similar cation exchange resins
without sorbitol have been reported [31-34]. In addition, intestinal necrosis has been
reported in patients receiving SPS in a reduced concentration (33 percent) of sorbitol [22].
Thus, intestinal necrosis appears to be a complication of SPS independent of sorbitol.
When given, SPS with or without sorbitol can be administered orally, and SPS without
sorbitol can be administered as a retention enema. Oral dosing is probably more effective if
intestinal motility is not impaired. The oral dose is usually 15 to 30 g, which can be repeated
every four to six hours as necessary. Single doses are probably less effective [35].

When given as an enema, 50 g of SPS is mixed with 150 mL of tap water (not sorbitol).
After cleansing enema with tap water at body temperature, the resin emulsion should be
administered at body temperature through a rubber tube placed at approximately 20 cm
from the rectum with the tip well into the sigmoid colon. The emulsion should be introduced
by gravity and flushed with an additional 50 to 100 mL of non-sodium-containing fluid. The
emulsion should be kept in the colon for at least 30 to 60 minutes and, preferably, two to
four hours, followed by a cleansing enema (250 to 1000 mL of tap water at body
temperature) [36]. The enema can be repeated every two to four hours, as necessary.

Despite modest efficacy and the risk of catastrophic consequences, SPS remains the most
widely used treatment for hyperkalemia [22,37]. In a six-month single-center survey from an
emergency department, 1001 patients received SPS in sorbitol, while only 188 received
other therapies [37].

Other therapies — Beta-2-adrenergic agonists (eg, inhaled albuterol) and intravenous

sodium bicarbonate have been studied as potential rapidly acting therapies to reduce the
serum potassium in hyperkalemic patients. Although they can be used in addition to
calcium, insulin (with glucose), and potassium removal therapy, they should not be used in
place of these treatments.

Beta-2-adrenergic agonists — Given the potential adverse effects described below, the

authors and reviewers of this topic believe that intravenous epinephrine should not be used
in the treatment of hyperkalemia. Albuterol is not frequently used but can be considered as
transient therapy in patients who have symptoms or serious ECG manifestations of
hyperkalemia despite therapy with calcium and insulin with glucose, or in patients in whom
dialysis is not appropriate or not feasible.

Like insulin, the beta-2-adrenergic agonists drive potassium into the cells by increasing the
activity of the Na-K-ATPase pump in skeletal muscle [1,38]. Beta-2-adrenergic receptors in
skeletal muscle also activate the inwardly directed Na-K-2Cl cotransporter, which may
account for as much as one-third of the uptake response to catecholamines [39].

Beta-2-adrenergic agonists can be effective in the acute treatment of hyperkalemia,

lowering the serum potassium concentration by 0.5 to 1.5 mEq/L [7,8,16,40,41]. Albuterol,
which is relatively selective for the beta-2-adrenergic receptors, can be given as 10 to 20 mg
in 4 mL of saline by nebulization over 10 minutes (which is 4 to 8 times the dose used for
bronchodilation). Alternatively and where available, albuterol 0.5 mg can be administered by
intravenous infusion. In patients who cannot tolerate nebulized albuterol, and if intravenous
therapy is not available, subcutaneous terbutaline is a potential alternative [41]. The peak
effect is seen within 30 minutes with intravenous infusion and at 90 minutes with
nebulization [40].

Albuterol and insulin with glucose have an additive effect, reducing serum potassium
concentration by approximately 1.2 to 1.5 mEq/L [7,14,42]. Thus, although albuterol should
not be used as monotherapy in hyperkalemic patients with end-stage renal disease (ESRD),
it can be added to insulin plus glucose to maximize the reduction in serum potassium [7].
One problem in patients on maintenance hemodialysis is that lowering the serum
potassium concentration by driving potassium into the cells can diminish subsequent
potassium removal during the dialysis session (from 50 to 29 mEq in one report), possibly
leading to rebound hyperkalemia after dialysis [43].

Potential side effects of the beta-2 agonists include mild tachycardia and the possible
induction of angina in susceptible subjects. Thus, these agents should probably be avoided
in patients with active coronary disease. In addition, all patients with ESRD should be
monitored carefully since they may have subclinical or overt coronary disease. (See "Risk
factors and epidemiology of coronary heart disease in end-stage renal disease (dialysis)".)

Sodium bicarbonate — Raising the systemic pH with sodium bicarbonate results in

hydrogen ion release from the cells as part of the buffering reaction. This change is
accompanied by potassium movement into the cells to maintain electroneutrality. The use
of bicarbonate for the treatment of hyperkalemia was mainly based upon small
uncontrolled clinical studies [44-46]. However, in a study that compared different
potassium-lowering modalities in 10 patients undergoing maintenance hemodialysis, a
bicarbonate infusion (isotonic or hypertonic) for up to 60 minutes had no effect on the
serum potassium concentration [16]. This lack of benefit was confirmed in several
subsequent studies of hemodialysis patients [47-49].

Given the limited efficacy, we do not recommend the administration of sodium bicarbonate
as the only therapy for the acute management of hyperkalemia, even in patients with mild
to moderate metabolic acidosis [16,47-49]. However, prolonged bicarbonate therapy
appears to be beneficial in patients with metabolic acidosis, particularly when administered
as an isotonic infusion rather than bolus ampules of hypertonic sodium bicarbonate [16]. In
one series, for example, the administration of isotonic sodium bicarbonate in a constant
infusion to patients with a baseline serum bicarbonate of 18 mEq/L had little effect at one
and two hours but significantly lowered the serum potassium from 6 mEq/L at baseline to
5.4 and 5.3 mEq/L at four and six hours, respectively; the serum bicarbonate increased to
28 mEq/L at one hour and 30 mEq/L at six hours [48].
In addition, acute or chronic bicarbonate (alkali) therapy may be warranted to treat acidemia
independent of hyperkalemia [45]. (See "Approach to the adult with metabolic acidosis",
section on 'Overview of therapy' and "Pathogenesis, consequences, and treatment of
metabolic acidosis in chronic kidney disease".)

When bicarbonate is given in the acute setting, we recommend the administration of an

isotonic solution (eg, 150 mEq in 1 L of 5 percent dextrose in water over two to four hours),
assuming the patient can tolerate the volume load. There is a potential hazard of giving
hypertonic solutions, such as the standard ampule of 50 mEq of sodium bicarbonate in 50
mL. In addition, multiple doses can lead to hypernatremia [16].

Over the long term, in patients with chronic kidney disease (CKD), there are a variety of
benefits from treating metabolic acidosis, and alkali therapy is recommended to maintain a
near-normal serum bicarbonate, independent of any effect on the serum potassium
concentration. (See "Pathogenesis, consequences, and treatment of metabolic acidosis in
chronic kidney disease", section on 'Treatment of metabolic acidosis in CKD'.)

PATIENTS WITHOUT A HYPERKALEMIC EMERGENCY — Identifying patients who do not

have a hyperkalemic emergency is presented above. (See 'Determining the urgency of
therapy' above.)

Patients who do not have a hyperkalemic emergency can generally be divided into two
groups (algorithm 1) (see 'Determining the urgency of therapy' above):

● Those who, despite needing to have their potassium lowered promptly, do not require
rapidly acting therapy with calcium and insulin with glucose. Such patients with severe
renal impairment are typically treated with dialysis (preferably hemodialysis) with or
without the use of a gastrointestinal cation exchanger (eg, patiromer). In patients with
normal renal function or mild to moderate renal impairment, correcting the cause of
hyperkalemia (eg, drugs, hypovolemia) will generally suffice, in addition to treatment
with saline infusion and loop diuretics.

● Those who can safely have their serum potassium lowered slowly. Such patients can
usually be treated with therapies that gradually reduce the serum potassium, such as a
low-potassium diet, loop or thiazide diuretics, or a reduction or cessation of medicines
that can increase the serum potassium. With the introduction of patiromer and
zirconium cyclosilicate (ZS-9), it is anticipated that gastrointestinal cation exchangers
will be utilized more frequently in these patients for chronic control of the serum
potassium.

Patients who need prompt serum potassium reduction — Identifying patients who should
have their serum potassium promptly lowered but who do not require rapidly acting therapy
(ie, calcium and insulin with glucose), is presented above. (See 'Determining the urgency of
therapy' above.)

Those with severe renal impairment — In patients with severe renal impairment who
need prompt serum potassium reduction, dialysis should be performed right away if it is
logistically feasible (ie, regular working hours, availability of staff, and presence of a
suitable vascular access). If prompt dialysis is not logistically feasible, then a
gastrointestinal cation exchanger (preferably patiromer or ZS-9, if and when available) can
be used to remove potassium from the body until such time that dialysis can be performed.
(See 'Gastrointestinal cation exchangers' below.)

Dialysis — Dialysis is indicated in hyperkalemic patients with severe renal impairment.

Hemodialysis is preferred since the rate of potassium removal is many times faster than
with peritoneal dialysis [50]. Hemodialysis can remove 25 to 50 mEq of potassium per hour,
with variability based upon the initial serum potassium concentration, the type and surface
area of the dialyzer used, the blood flow rate, the dialysate flow rate, the duration of dialysis,
the potassium concentration of the dialysate, and the patient's muscle mass [1,12].

One of the major determinants of the rate of potassium removal is the potassium gradient
between the plasma and dialysate. Issues related to the removal of potassium with
hemodialysis and potential adverse effects are discussed in detail separately. (See "Acute
hemodialysis prescription".)

A rebound increase in serum potassium concentration occurs after hemodialysis in all

patients in whom potassium is removed since the reduction in serum potassium during
dialysis creates a gradient for potassium movement out of the cells. The magnitude of this
effect was evaluated in a study of 14 stable maintenance hemodialysis patients [51]. The
average serum potassium concentrations at baseline, during hemodialysis, and up to six
hours after hemodialysis were 5.7, 3.6, and 5 mEq/L, respectively. Thus, the serum
potassium concentration should usually not be measured soon after the completion of
hemodialysis, since the results are likely to be misleading.

The postdialysis rebound after hemodialysis is more pronounced in patients undergoing

acute hemodialysis for hyperkalemia due to massive release of potassium from injured
cells (eg, tumor lysis, rhabdomyolysis) and after regular maintenance hemodialysis in
patients with a high predialysis serum potassium concentration [51].

Rapidly acting transient therapies given before dialysis, such as insulin with glucose or
albuterol, have a twofold effect: Total potassium removal is reduced due to lowering of the
serum potassium concentration [43,52]; and the potassium rebound is greater because of
the wearing off of the effect of the transient therapies. The potassium rebound is also
increased with a high-sodium dialysate since the increase in plasma osmolality creates a
gradient for water and then potassium efflux from the cells [53].

Patients who have a large postdialysis rebound may require daily dialysis or continuous
renal replacement therapy to avoid recurrent severe hyperkalemia.

Those without severe renal impairment — Patients who have moderate hyperkalemia

and either normal renal function or mild to moderate renal impairment can usually be
managed without dialysis. Treatment of such patients typically includes a gastrointestinal
cation exchanger in addition to reversing the cause of hyperkalemia. As an example, a
patient with moderate chronic kidney disease (CKD) treated with a renin-angiotensin-
aldosterone system (RAAS) inhibitor who presents with a serum potassium of 6.0 mEq/L
may be treated with a cation exchanger (such as patiromer), temporary discontinuation of
the RAAS inhibitor, as well as other therapies that are appropriate for the clinical setting (ie,
bicarbonate therapy if the patient has metabolic acidosis, and diuretic therapy if the patient
is hypervolemic).

Patients who can have the serum potassium lowered slowly — Identifying patients who do
not need prompt lowering of the serum potassium and can be safely treated with therapy
that gradually lowers the serum potassium is presented above. (See 'Determining the
urgency of therapy' above.)

In addition to correcting reversible causes of hyperkalemia, our approach in such patients is

as follows:

● All such patients should receive dietary counseling to reduce potassium intake (table
5). (See "Patient education: Low-potassium diet (The Basics)" and "Patient education:
Low-potassium diet (Beyond the Basics)" and 'Dietary modification' below.)

● In addition, thiazide or loop diuretics can be used in patients who have hypertension or
hypervolemia. (See 'Diuretics' below.)

● Patients who continue to have moderate hyperkalemia despite dietary modification and
diuretics can be treated chronically with newer gastrointestinal cation exchangers (eg,
patiromer). (See 'Gastrointestinal cation exchangers' below.)

Dietary modification — It is rare for hyperkalemia to occur exclusively due to excessive

intake, although such cases have been described [54,55]. By contrast, the presence of renal
disease predisposes to hyperkalemia in patients consuming potassium [56]. In addition to
renal impairment, other predisposing factors include hypoaldosteronism and drugs that
inhibit the RAAS can result in significant hyperkalemia after only modest intake of
potassium. Such patients should be assessed for their intake of potassium-rich foods (refer
to https://www.kidney.org/atoz/content/potassium), and counseled to avoid these foods
(table 6). Other, occult sources of excessive potassium include salt substitutes [57,58],
various forms of pica [59], and "alternative" nutritional therapies [60,61]. Often, the adoption
of a potassium-restricted diet (refer to https://www.kidney.org/atoz/content/potassium)
normalizes serum potassium levels and affords the resumption of RAAS antagonists (table
7), even in patients with CKD.

Diuretics — Loop and thiazide diuretics increase potassium loss in the urine in patients
with normal or mild to moderately impaired renal function, particularly when combined with
saline hydration to maintain distal sodium delivery and flow. However, patients with
persistent hyperkalemia typically have impaired renal potassium secretion, and there are no
data demonstrating a clinically important short-term kaliuretic response to diuretic therapy.

Although data are limited, chronic diuretic therapy is probably effective over the long term
by increasing urinary potassium excretion, particularly in patients with mild to moderate
CKD [62]. For patients with moderate hyperkalemia whose renal function is not severely
impaired, we suggest a trial of diuretics if otherwise appropriate (eg, hypertension or
hypervolemia). Among patients with hyperkalemia due to angiotensin inhibitors, many can
be controlled with a low-potassium diet and diuretic therapy.

Gastrointestinal cation exchangers — Patiromer and ZS-9 are nonabsorbable

compounds that exchange calcium or sodium and hydrogen, respectively. We do not use
sodium polystyrene sulfonate (a cation exchange resin) as chronic therapy for such
patients.

Patiromer — Patiromer is a spherical, nonabsorbable organic polymer, formulated as

a powder for suspension, which binds potassium in the colon in exchange for calcium
[63,64].

In a phase II, open-label dose-finding trial (AMETHYST-DN), 306 diabetic patients with an
estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 and either mild or
moderate hyperkalemia (serum potassium of 5.1 to 5.5, or 5.6 to 5.9 mEq/L, respectively)
were randomly assigned to a range of initial patiromer doses (4.2 g twice daily to 16.8 g
twice daily) [65]; follow-up was 52 weeks. All patients were also treated with stable doses
of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker
(ARB), or both, often in combination with spironolactone. At four weeks, the change in
serum potassium from baseline ranged from -0.35 to -0.55 mEq/L with initial doses of 4.2 g
twice daily to 12.6 g twice daily among those with mild hyperkalemia, and from -0.87 to
-0.97 mEq/L with initial doses of 8.4 g twice daily to 12.6 g twice daily among those with
moderate hyperkalemia. Approximately one-third of patients had a single adjustment (up or
down) to their patiromer dose; most required no adjustment. At 52 weeks, serum potassium
concentrations remained in the normal range with continued patiromer therapy.
Discontinuation of patiromer resulted in an increase in the serum potassium within three
days.

There were no treatment-related serious adverse events in AMETHYST-DN. The most

common treatment-related side effects included constipation (6.3 percent of patients) and
hypomagnesemia (8.6 percent of patients). Hypomagnesemia occurred more commonly
with higher doses of patiromer (16.7 percent among those assigned 33.6 g/day compared
with 5.4 percent among those assigned 8.4 g/day). Severe hypomagnesemia (a serum
magnesium <1.2 mg/dL) developed in 13 patients (4.3 percent).

The OPAL-HK study extended these observations in a phase III, randomized placebo-
controlled trial in outpatients with CKD and hyperkalemia [66]. In OPAL-HK, 243 patients
with an eGFR of 15 to 59 mL/min/1.73 m2 and a serum potassium of 5.1 to 6.4 mEq/L on
two occasions while receiving a stable dose of an ACE inhibitor or ARB received either 4.2
or 8.4 g of patiromer twice daily for four weeks, depending upon whether their serum
potassium was below or above 5.5 mEq/L. The mean decrease in serum potassium at four
weeks was 1.0 mEq/L (0.6 and 1.2 mEq/L with lower and higher doses, respectively);
approximately 75 percent of patients achieved the target serum potassium of 3.8 to 5.0
mEq/L. The decline in serum potassium was steepest during the first three days.

The 107 patients whose baseline serum potassium was 5.5 mEq/L or greater and who
achieved the target serum potassium during the initial four-week treatment period were
randomly assigned to patiromer or placebo for another eight weeks. Serum potassium
remained the same in patients continuing patiromer and increased by 0.7 mEq/L in those
assigned to placebo. The incidence of hyperkalemia (5.5 mEq/L or greater) was
significantly higher in the placebo group (60 versus 15 percent). Serious adverse events
were rare and not likely to be related to treatment; constipation was the most common side
effect, occurring in 11 percent of patients during the initial four-week period. As with the
AMETHYST-DN trial, hypomagnesemia developed in some patients (eight patients [3
percent] developed magnesium levels <1.4 mg/dL).

There are several limitations of the OPAL-HK and AMETHYST-DN trials. The effect of
patiromer in patients with acute hyperkalemia or end-stage renal disease (ESRD) was not
evaluated. In addition, patients in these trials were not routinely prescribed a low-potassium
diet, only one-half of patients in the OPAL-HK trial were receiving loop or thiazide diuretics,
and the number of patients in the AMETHYST-DN trial who received diuretics was not
reported. Both a low-potassium diet and the use of loop or thiazide diuretics can be long-
term strategies to prevent hyperkalemia in many patients with CKD who are treated with
ACE inhibitors or ARBs. (See 'Diuretics' above.)

In addition to binding cations, patiromer can bind other drugs in the gastrointestinal tract.
Clinically important interactions with ciprofloxacin, thyroxine, and metformin have been
identified; these three drugs need to be administered more than three hours before or after
patiromer [67].

Zirconium cyclosilicate — Sodium zirconium cyclosilicate (ZS-9) is an inorganic,

nonabsorbable crystalline compound that exchanges both sodium and hydrogen ions for
potassium throughout its intestinal transit [63]. The efficacy of ZS-9 in hyperkalemic
outpatients was evaluated in two nearly identical phase III, randomized placebo-controlled
trials:

● In the Hyperkalemia Randomized Intervention Multidose ZS-9 Maintenance

(HARMONIZE) study, 258 adult patients with persistent hyperkalemia (serum
potassium that is greater than or equal to 5.1 mEq/L) entered a 48-hour open-label run-
in during which they received 10 g of ZS-9 three times daily; 69 percent had CKD
(although patients with ESRD were excluded), 70 percent were taking a renin-
angiotensin system inhibitor, and the majority had heart failure, diabetes mellitus, or
both [68]. Of the 258 patients who entered the open-label run-in, 237 (92 percent)
achieved a normal serum potassium (3.5 to 5.0 mEq/L) at 48 hours and were then
randomly assigned to placebo or 5 g, 10 g, or 15 g of ZS-9 once daily for four weeks.
During randomized therapy, the mean serum potassium was significantly lower with
ZS-9 (4.8, 4.5, and 4.4 mEq/L with 5, 10, and 15 g dosing, respectively) as compared
with placebo (5.1 mEq/L). Similarly, the proportion of normokalemic patients at the end
of the study was significantly greater with ZS-9 (71 to 85 percent as compared with 48
percent with placebo). Serious adverse events were uncommon and were not
significantly increased with ZS-9. However, edema was more common with the 10 g
and 15 g doses compared with placebo (6 and 14 versus 2 percent), as was
hypokalemia (10 and 11 versus 0 percent). Among a subgroup of 87 patients with heart
failure, edema occurred in eight (15 percent) of those receiving ZS-9 and in one (4
percent) receiving placebo [69]. It is unclear whether or not higher edema rates with ZS-
9 are due to an increased sodium load (which, as noted above, would be expected
since ZS-9 exchanges sodium for potassium).

● In another trial, 753 adult patients with a serum potassium of 5.0 to 6.5 mEq/L were
randomly assigned to receive 1.25, 2.5, 5, or 10 g of ZS-9 three times daily for 48 hours;
74 percent had CKD (patients with ESRD were excluded), 67 percent were receiving a
renin-angiotensin system inhibitor, and most patients had diabetes, heart failure, or
both [70]. A normal serum potassium (3.5 to 4.9 mEq/L) at 48 hours was attained by
543 patients (72 percent), and these individuals were then reassigned to receive
placebo or 1.25, 2.5, 5, or 10 g of ZS-9 once daily for two weeks. The serum potassium
at two weeks was significantly lower in patients receiving 5 and 10 g doses of ZS-9 as
compared with placebo (by approximately 0.3 and 0.5 mEq/L, respectively) but not with
1.25 and 2.5 g doses. Adverse events were similar with placebo and ZS-9.
In these trials, the steepest decline in serum potassium with ZS-9 occurred during the first
four hours of therapy [68,70]. This suggests an acute effect on intestinal potassium
secretion, rather than simply a reduction in potassium absorption. Neither trial evaluated
the long-term efficacy and safety of ZS-9, and neither studied patients with acute
hyperkalemia or ESRD.

Do not use SPS or other resins — The most widely used cation exchange resin has
been sodium polystyrene sulfonate (SPS). Although "SPS" is often used as an abbreviation
for sodium polystyrene sulfonate, SPS is actually a brand name for sodium polystyrene
sulfonate in sorbitol.

Cation exchange resins do not appear to be more effective in removing potassium from the
body than laxative therapy. Although uncommon, cation exchange resins can produce
severe side effects, particularly intestinal necrosis, which may be fatal. (See 'SPS in rare
settings' above.)

Given these concerns, SPS or other resins should not be used in patients with chronic mild
or moderate hyperkalemia who do not have a hyperkalemic emergency and who do not
require a prompt reduction in serum potassium. (See 'Determining the urgency of therapy'
above.)

DRUG-INDUCED HYPERKALEMIA — A variety of drugs can raise the serum potassium,

primarily by interfering with the renin-angiotensin-aldosterone system. Probably the most
common are angiotensin inhibitors (eg, angiotensin-converting enzyme [ACE] inhibitors and
angiotensin II receptor blockers [ARBs]), aldosterone antagonists and other potassium
sparing diuretics (eg, spironolactone, eplerenone, and amiloride), digitalis, and nonsteroidal
anti-inflammatory drugs (table 3). (See "Causes and evaluation of hyperkalemia in adults",
section on 'Reduced aldosterone secretion'.)

These drugs should be discontinued, or the dose reduced at least temporarily, until the
hyperkalemia is controlled.

PREVENTION — There are several measures that can help to prevent hyperkalemia in

patients with chronic kidney disease (CKD), particularly those with end-stage renal disease
(ESRD). In addition to a low-potassium diet, the following modalities have been effective in
stable maintenance hemodialysis patients (see "Patient education: Low-potassium diet
(Beyond the Basics)"):

● Avoid episodes of fasting, which can increase potassium movement out of the cells
due, at least in part, to reduced insulin secretion [8,71]. In a study of 10 stable patients
on maintenance hemodialysis who did not have diabetes mellitus, fasting for 18 hours
led to a mean 0.6 mEq/L rise in the serum potassium concentration, which was
completely prevented when the protocol was repeated with the administration of low-
 dose insulin with dextrose [71]. Thus, nondiabetic patients with ESRD who are
undergoing elective surgery should, if they are in the hospital, receive parenteral
glucose-containing solutions when fasting overnight.

● Avoid, if possible, drugs that raise the serum potassium concentration in patients with
a serum potassium ≥5.5 mEq/L. These include inhibitors of the renin-angiotensin-
aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE) inhibitors,
angiotensin II receptor blockers (ARBs), direct renin inhibitors, aldosterone antagonists,
and nonselective beta blockers (eg, propranolol and labetalol) [72,73]. Beta-1-selective
blockers such as metoprolol and atenolol are much less likely to cause hyperkalemia
[8,74]. (See "Causes and evaluation of hyperkalemia in adults", section on 'Beta
blockers'.)

Patients with CKD or heart failure are often treated with RAAS inhibitors. A variety of
preventive measures can diminish the risk of hyperkalemia [72]. These include:

● Close monitoring of the serum potassium concentration and estimated glomerular

filtration rate (eGFR), particularly after changes in RAAS inhibitor therapy.

● Dietary restriction of potassium. (See "Patient education: Low-potassium diet (Beyond

the Basics)".)

● Avoidance or discontinuation of other drugs that impair potassium excretion (eg,

nonsteroidal anti-inflammatory drugs).

● The utilization of low initial doses and evidence-based final doses of RAAS inhibitors
for specific indications (eg, heart failure, proteinuric CKD). The dose should be reduced
with moderate hyperkalemia (serum potassium of ≤5.5 mEq/L) and therapy should be
discontinued if the serum potassium rises above 5.5 mEq/L unless the serum
potassium can be reduced by diuretic therapy.

● The use of thiazide or loop diuretics whenever otherwise indicated.

● There are no good data on the chronic efficacy of oral alkali therapy (sodium
bicarbonate or sodium citrate) for the treatment of persistent hyperkalemia. Most such
patients have CKD with or without hypoaldosteronism. There are a variety of benefits
from treating metabolic acidosis in such patients, and alkali therapy is typically
recommended, independent of any effect on the serum potassium concentration. (See
"Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney
disease", section on 'Treatment of metabolic acidosis in CKD'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from

selected countries and regions around the world are provided separately. (See "Society
guideline links: Fluid and electrolyte disorders".)

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 topics (see "Patient education: Hyperkalemia (The Basics)" and "Patient
education: Low-potassium diet (The Basics)")

● Beyond the Basics topic (see "Patient education: Low-potassium diet (Beyond the
Basics)")

SUMMARY AND RECOMMENDATIONS

● The urgency of treatment of hyperkalemia varies with the presence or absence of the
symptoms and signs associated with hyperkalemia, the severity of the potassium
elevation, and the cause of hyperkalemia. Our approach to therapeutic urgency is as
follows (algorithm 1) (see 'Determining the urgency of therapy' above):

• Hyperkalemic emergency − Patients who have clinical signs or symptoms of

hyperkalemia (eg, muscle weakness or paralysis, cardiac conduction
abnormalities, cardiac arrhythmias), patients with severe hyperkalemia (serum
potassium >6.5 mEq/L), and patients with moderate hyperkalemia (serum
potassium >5.5 mEq/L) plus significant renal impairment and ongoing tissue
breakdown or potassium absorption) have a hyperkalemic emergency.

• Patients needing prompt therapy − Some patients with moderate hyperkalemia but
without a hyperkalemic emergency should, nonetheless, have their potassium
lowered promptly (ie, within 6 to 12 hours). Such patients include hemodialysis
patients who present outside of regular dialysis hours, patients with marginal renal
function and/or marginal urine output, or hyperkalemic patients who need to be
optimized for surgery.
 • Patients who can have the potassium lowered slowly − Most patients with
hyperkalemia have chronic, mild (≤5.5 mEq/L) or moderate (5.5 to 6.5 mEq/L)
elevations in serum potassium due to chronic kidney disease (CKD) or the use of
medications that inhibit the renin-angiotensin-aldosterone system ([RAAS] or
both). Such patients do not require urgent lowering of the serum potassium.

● Patients with a hyperkalemic emergency should receive (table 1) (see 'Patients with a
hyperkalemic emergency' above):

• Intravenous calcium to antagonize the membrane actions of hyperkalemia. (See

'Calcium' above.)

• Intravenous insulin (typically given with intravenous glucose) to drive extracellular

potassium into cells. (See 'Insulin with glucose' above.)

• Therapy to rapidly remove excess potassium from the body (ie, loop or thiazide
diuretics if renal function is not severely impaired, a gastrointestinal cation
exchanger, and/or dialysis [preferably hemodialysis] if renal function is severely
impaired). (See 'Remove potassium from the body' above.)

• Treatment of reversible causes of hyperkalemia, such as correcting hypovolemia

and discontinuing drugs that increase the serum potassium (eg, nonsteroidal anti-
inflammatory drugs [NSAIDs], inhibitors of the RAAS). (See "Causes and evaluation
of hyperkalemia in adults" and 'Drug-induced hyperkalemia' above.)

• Continuous cardiac monitoring and serial electrocardiograms (ECGs). The serum

potassium should be measured at one to two hours after the initiation of
treatment. The timing of further measurements is determined by the serum
potassium concentration and the response to therapy. Patients who receive
insulin, with or without dextrose, should undergo hourly glucose measurements for
up to six hours in order to monitor for hypoglycemia. (See 'Monitoring' above.)

● Treatment of patients who do not have a hyperkalemic emergency generally depends

upon how promptly the serum potassium should be lowered (algorithm 1) (see
'Patients without a hyperkalemic emergency' above):

• Patients needing prompt potassium lowering are typically treated with

hemodialysis (if they have severe renal dysfunction) with or without the use of a
gastrointestinal cation exchanger (eg, patiromer). In patients with normal renal
function or mild to moderate renal impairment, correcting the cause of
hyperkalemia (eg, drugs, hypovolemia) will generally suffice, in addition to
treatment with saline infusion and loop diuretics; a gastrointestinal cation
 exchanger is sometimes used in such patients. (See 'Patients who need prompt
serum potassium reduction' above.)

• Patients who can safely have their serum potassium lowered slowly are usually
treated with therapies that gradually reduce the serum potassium, such as a low-
potassium diet, loop or thiazide diuretics, or a reduction or cessation of medicines
that can increase the serum potassium. With the introduction of patiromer and ZS-
9, it is anticipated that gastrointestinal cation exchangers will be utilized more
frequently in these patients for chronic control of the serum potassium. (See
'Patients who can have the serum potassium lowered slowly' above.)

● There are several measures that can help to prevent hyperkalemia or worsening of
hyperkalemia in patients with CKD, particularly those with end-stage renal disease
(ESRD). In addition to a low-potassium diet, the following modalities have been
effective in stable maintenance hemodialysis patients (see 'Prevention' above and
"Patient education: Low-potassium diet (Beyond the Basics)"):

• Avoid episodes of fasting, which can increase potassium movement out of the
cells due, at least in part, to reduced insulin secretion.

• In patients with moderate hyperkalemia, avoid, if possible, drugs that raise the
serum potassium concentration. These include RAAS inhibitors, such as
angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers
(ARBs), direct renin inhibitors, aldosterone antagonists, and nonselective beta
blockers (eg, propranolol and labetalol) (table 3).

• Avoidance or discontinuation of other drugs that impair potassium excretion (eg,

NSAIDs).

• The use of thiazide or loop diuretics whenever otherwise indicated.

REFERENCES

1. Mount DB, Zandi-Nejad K. Disorders of potassium balance. In: Brenner and Recto
r's The Kidney, 8th ed, Brenner BM (Ed), WB Saunders Co, Philadelphia 2008. p.547.
2. Kamel KS, Wei C. Controversial issues in the treatment of hyperkalaemia. Nephrol
Dial Transplant 2003; 18:2215.
3. Winkler AW, Hoff HE, Smith PK. Factors affecting the toxicity of potassium. Am J
Physiol 1939; 127:430.
4. BRAUN HA, VAN HORNE R, BETTINGER JC, BELLET S. The influence of
hypocalcemia induced by sodium ethylenediamine tetraacetate on the toxicity of
potassium; an experimental study. J Lab Clin Med 1955; 46:544.
 5. Ferrannini E, Taddei S, Santoro D, et al. Independent stimulation of glucose
metabolism and Na+-K+ exchange by insulin in the human forearm. Am J Physiol
1988; 255:E953.
6. Pergola PE, DeFronzo R. Clinical disorders of hyperkalemia. In: The Kidney: Physiol
ogy and Pathophysiology, Seldin DW, Giebisch G (Eds), Lippincott Williams & Wilkin
s, 2000. Vol 2, p.1647.
7. Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in
hemodialysis patients. Kidney Int 1990; 38:869.
8. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management.
J Am Soc Nephrol 1995; 6:1134.
9. Goldfarb S, Strunk B, Singer I, Goldberg M. Paradoxical glucose-induced
hyperkalemia. Combined aldosterone-insulin deficiency. Am J Med 1975; 59:744.
10. Nicolis GL, Kahn T, Sanchez A, Gabrilove JL. Glucose-induced hyperkalemia in
diabetic subjects. Arch Intern Med 1981; 141:49.
11. Magnus Nzerue C, Jackson E. Intractable life-threatening hyperkalaemia in a
diabetic patient. Nephrol Dial Transplant 2000; 15:113.
12. Ahmed J, Weisberg LS. Hyperkalemia in dialysis patients. Semin Dial 2001; 14:348.
13. Kim HJ, Han SW. Therapeutic approach to hyperkalemia. Nephron 2002; 92 Suppl
1:33.
14. Lens XM, Montoliu J, Cases A, et al. Treatment of hyperkalaemia in renal failure:
salbutamol v. insulin. Nephrol Dial Transplant 1989; 4:228.
15. Emmett M. Non-dialytic treatment of acute hyperkalemia in the dialysis patient.
Semin Dial 2000; 13:279.
16. Blumberg A, Weidmann P, Shaw S, Gnädinger M. Effect of various therapeutic
approaches on plasma potassium and major regulating factors in terminal renal
failure. Am J Med 1988; 85:507.
17. De Wolf A, Frenette L, Kang Y, Tang C. Insulin decreases the serum potassium
concentration during the anhepatic stage of liver transplantation. Anesthesiology
1993; 78:677.
18. Alvestrand A, Wahren J, Smith D, DeFronzo RA. Insulin-mediated potassium uptake
is normal in uremic and healthy subjects. Am J Physiol 1984; 246:E174.
19. Goecke IA, Bonilla S, Marusic ET, Alvo M. Enhanced insulin sensitivity in extrarenal
potassium handling in uremic rats. Kidney Int 1991; 39:39.
20. Mistry M, Shea A, Giguère P, Nguyen ML. Evaluation of Sodium Polystyrene
Sulfonate Dosing Strategies in the Inpatient Management of Hyperkalemia. Ann
Pharmacother 2016; 50:455.
21. Hagan AE, Farrington CA, Wall GC, Belz MM. Sodium polystyrene sulfonate for the
treatment of acute hyperkalemia: a retrospective study. Clin Nephrol 2016; 85:38.
22. Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the
treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol 2010;
21:733.
23. Gerstman BB, Kirkman R, Platt R. Intestinal necrosis associated with postoperative
orally administered sodium polystyrene sulfonate in sorbitol. Am J Kidney Dis
1992; 20:159.
24. McGowan CE, Saha S, Chu G, et al. Intestinal necrosis due to sodium polystyrene
sulfonate (Kayexalate) in sorbitol. South Med J 2009; 102:493.
25. Lillemoe KD, Romolo JL, Hamilton SR, et al. Intestinal necrosis due to sodium
polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for
the hypothesis. Surgery 1987; 101:267.
26. Rashid A, Hamilton SR. Necrosis of the gastrointestinal tract in uremic patients as
a result of sodium polystyrene sulfonate (Kayexalate) in sorbitol: an
underrecognized condition. Am J Surg Pathol 1997; 21:60.
27. Scott TR, Graham SM, Schweitzer EJ, Bartlett ST. Colonic necrosis following
sodium polystyrene sulfonate (Kayexalate)-sorbitol enema in a renal transplant
patient. Report of a case and review of the literature. Dis Colon Rectum 1993;
36:607.
28. Wootton FT, Rhodes DF, Lee WM, Fitts CT. Colonic necrosis with Kayexalate-
sorbitol enemas after renal transplantation. Ann Intern Med 1989; 111:947.
29. https://www.fda.gov/Drugs/DrugSafety/ucm572484.htm.
30. Ayoub I, Oh MS, Gupta R, et al. Colon Necrosis Due to Sodium Polystyrene
Sulfonate with and without Sorbitol: An Experimental Study in Rats. PLoS One
2015; 10:e0137636.
31. Cheng ES, Stringer KM, Pegg SP. Colonic necrosis and perforation following oral
sodium polystyrene sulfonate (Resonium A/Kayexalate in a burn patient. Burns
2002; 28:189.
32. Goutorbe P, Montcriol A, Lacroix G, et al. Intestinal Necrosis Associated with Orally
Administered Calcium Polystyrene Sulfonate Without Sorbitol. Ann Pharmacother
2011; 45:e13.
33. Rugolotto S, Gruber M, Solano PD, et al. Necrotizing enterocolitis in a 850 gram
infant receiving sorbitol-free sodium polystyrene sulfonate (Kayexalate): clinical
and histopathologic findings. J Perinatol 2007; 27:247.
34. Joo M, Bae WK, Kim NH, Han SR. Colonic mucosal necrosis following
administration of calcium polystryrene sulfonate (Kalimate) in a uremic patient. J
 Korean Med Sci 2009; 24:1207.
35. Gruy-Kapral C, Emmett M, Santa Ana CA, et al. Effect of single dose resin-cathartic
therapy on serum potassium concentration in patients with end-stage renal
disease. J Am Soc Nephrol 1998; 9:1924.
36. Gales MA, Gales BJ, Dyer ME, Orr SR. Rectally administered sodium polystyrene
sulfonate. Am J Health Syst Pharm 1995; 52:2813.
37. Joshi P, Beaulieu J, Shemin D. The effect of a single dose of polystyrene sulfonate
(SPS) in hyperkalemic patients with kidney disease (abstract). J Am Soc Nephrol
2008; 19:335A.
38. Clausen T, Everts ME. Regulation of the Na,K-pump in skeletal muscle. Kidney Int
1989; 35:1.
39. Gosmanov AR, Wong JA, Thomason DB. Duality of G protein-coupled mechanisms
for beta-adrenergic activation of NKCC activity in skeletal muscle. Am J Physiol
Cell Physiol 2002; 283:C1025.
40. Liou HH, Chiang SS, Wu SC, et al. Hypokalemic effects of intravenous infusion or
nebulization of salbutamol in patients with chronic renal failure: comparative
study. Am J Kidney Dis 1994; 23:266.
41. Sowinski KM, Cronin D, Mueller BA, Kraus MA. Subcutaneous terbutaline use in
CKD to reduce potassium concentrations. Am J Kidney Dis 2005; 45:1040.
42. Ahee P, Crowe AV. The management of hyperkalaemia in the emergency
department. J Accid Emerg Med 2000; 17:188.
43. Allon M, Shanklin N. Effect of albuterol treatment on subsequent dialytic
potassium removal. Am J Kidney Dis 1995; 26:607.
44. BURNELL JM, SCRIBNER BH, UYENO BT, VILLAMIL MF. The effect in humans of
extracellular pH change on the relationship between serum potassium
concentration and intracellular potassium. J Clin Invest 1956; 35:935.
45. SCHWARZ KC, COHEN BD, LUBASH GD, RUBIN AL. Severe acidosis and
hyperpotassemia treated with sodium bicarbonate infusion. Circulation 1959;
19:215.
46. Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant
blood pH. Kidney Int 1977; 12:354.
47. Gutierrez R, Schlessinger F, Oster JR, et al. Effect of hypertonic versus isotonic
sodium bicarbonate on plasma potassium concentration in patients with end-
stage renal disease. Miner Electrolyte Metab 1991; 17:297.
48. Blumberg A, Weidmann P, Ferrari P. Effect of prolonged bicarbonate administration
on plasma potassium in terminal renal failure. Kidney Int 1992; 41:369.
49. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in
dialysis patients: interactions with insulin and albuterol. Am J Kidney Dis 1996;
28:508.
50. Nolph KD, Popovich RP, Ghods AJ, Twardowski Z. Determinants of low clearances
of small solutes during peritoneal dialysis. Kidney Int 1978; 13:117.
51. Blumberg A, Roser HW, Zehnder C, Müller-Brand J. Plasma potassium in patients
with terminal renal failure during and after haemodialysis; relationship with dialytic
potassium removal and total body potassium. Nephrol Dial Transplant 1997;
12:1629.
52. Allon M. Medical and dialytic management of hyperkalemia in hemodialysis
patients. Int J Artif Organs 1996; 19:697.
53. De Nicola L, Bellizzi V, Minutolo R, et al. Effect of dialysate sodium concentration
on interdialytic increase of potassium. J Am Soc Nephrol 2000; 11:2337.
54. John SK, Rangan Y, Block CA, Koff MD. Life-threatening hyperkalemia from
nutritional supplements: uncommon or undiagnosed? Am J Emerg Med 2011;
29:1237.e1.
55. Parisi A, Alabiso A, Sacchetti M, et al. Complex ventricular arrhythmia induced by
overuse of potassium supplementation in a young male football player. Case
report. J Sports Med Phys Fitness 2002; 42:214.
56. Smillie WG. Potassium poisoning in nephritis. Arch Intern Med 1915; 16:330.
57. Doorenbos CJ, Vermeij CG. Danger of salt substitutes that contain potassium in
patients with renal failure. BMJ 2003; 326:35.
58. Sopko JA, Freeman RM. Salt substitutes as a source of potassium. JAMA 1977;
238:608.
59. Abu-Hamdan DK, Sondheimer JH, Mahajan SK. Cautopyreiophagia. Cause of life-
threatening hyperkalemia in a patient undergoing hemodialysis. Am J Med 1985;
79:517.
60. Nagasaki A, Takamine W, Takasu N. Severe hyperkalemia associated with
"alternative" nutritional cancer therapy. Clin Nutr 2005; 24:864.
61. Mueller BA, Scott MK, Sowinski KM, Prag KA. Noni juice (Morinda citrifolia): hidden
potential for hyperkalemia? Am J Kidney Dis 2000; 35:310.
62. Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-
converting enzyme inhibitors. How much should we worry? Arch Intern Med 1998;
158:26.
63. Ingelfinger JR. A new era for the treatment of hyperkalemia? N Engl J Med 2015;
372:275.
 64. Bushinsky DA, Spiegel DM, Gross C, et al. Effect of Patiromer on Urinary Ion
Excretion in Healthy Adults. Clin J Am Soc Nephrol 2016; 11:1769.
65. Bakris GL, Pitt B, Weir MR, et al. Effect of Patiromer on Serum Potassium Level in
Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN
Randomized Clinical Trial. JAMA 2015; 314:151.
66. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease
and hyperkalemia receiving RAAS inhibitors. N Engl J Med 2015; 372:211.
67. Lesko LJ, Offman E, Brew CT, et al. Evaluation of the Potential for Drug Interactions
With Patiromer in Healthy Volunteers. J Cardiovasc Pharmacol Ther 2017; 22:434.
68. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium
cyclosilicate on potassium lowering for 28 days among outpatients with
hyperkalemia: the HARMONIZE randomized clinical trial. JAMA 2014; 312:2223.
69. Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with
sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a
phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail 2015;
17:1050.
70. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in
hyperkalemia. N Engl J Med 2015; 372:222.
71. Allon M, Takeshian A, Shanklin N. Effect of insulin-plus-glucose infusion with or
without epinephrine on fasting hyperkalemia. Kidney Int 1993; 43:212.
72. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-
aldosterone system. N Engl J Med 2004; 351:585.
73. Knoll GA, Sahgal A, Nair RC, et al. Renin-angiotensin system blockade and the risk
of hyperkalemia in chronic hemodialysis patients. Am J Med 2002; 112:110.
74. Castellino P, Bia MJ, DeFronzo RA. Adrenergic modulation of potassium
metabolism in uremia. Kidney Int 1990; 37:793.

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