Hyperkalemia (Treatment and prevention)

INTRODUCTION
1.

2.

Hyperkalemia is common clinical problem that is most often result of impaired urinary
potassium excretion due to AKI or CKD and/or disorders or drugs that inhibit RAAS. Therapy
for hyperkalemia due to potassium retention is ultimately aimed at inducing potassium loss.
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 (DKA or HHS). In these disorders, hyperosmolality and
insulin deficiency are primarily responsible for transcellular shift of potassium from cells into
ECF, which can be reversed by administration of fluids and insulin. Many of these patients
have significant deficit in whole body potassium and must be monitored carefully for the
development of hypokalemia during therapy.

3.

The treatment and prevention of hyperkalemia will be reviewed here. The causes, diagnosis,
and clinical manifestations of hyperkalemia are discussed separately.
URGENCY OF THERAPY
1. The urgency of treatment of hyperkalemia varies with cause and presence or absence of
symptoms and signs associated with hyperkalemia. In addition, patients with marked tissue
breakdown (rhabdomyolysis, crush injury, tumor lysis syndrome) release large amounts of
potassium from cells, which can lead to rapid and substantial elevations in serum potassium.
Thus, these patients should receive aggressive therapy to remove potassium even if there is
only mild degree of hyperkalemia.
2. The most serious manifestations of hyperkalemia are muscle weakness or paralysis, cardiac

3.

4.

conduction abnormalities, and cardiac arrhythmias, including sinus bradycardia, sinus arrest,
slow idioventricular rhythms, VT, Vf, and asystole. These manifestations usually occur when
[K] is 7.0 meq/L with chronic hyperkalemia or possibly at lower levels with acute rise in
serum potassium.
The clinical manifestations typically occur in patients who have one or more of the
characteristic ECG abnormalities associated with hyperkalemia. A tall peaked T wave with
shortened QT interval is the earliest change, followed by progressive lengthening of PR
interval and QRS duration. The P wave may disappear, and ultimately the QRS widens further
to sine wave. Ventricular standstill with flat line on ECG ensues with complete absence of
electrical activity. The progression and severity of ECG changes do not correlate with [K].
There are three approaches to the treatment of hyperkalemia (table 1).
A.
B.
C.

Antagonizing membrane effects of potassium with calcium

Driving extracellular potassium into cells
Removing excess potassium from body

RAPIDLY ACTING TRANSIENT THERAPIES

1. The following modalities are generally listed according to their rapidity of action. These

2.

3.

4.

approaches provide time for initiation of therapies that remove excess potassium (cation
exchange resin or dialysis). A summary table to facilitate emergent management is provided
(table 2).
Indications for use
A. Rapidly acting therapies include administration of calcium, insulin with glucose,
2-adrenergic agonists, and, in selected patients, sodium bicarbonate. These therapies
are primarily used in three settings.
i.
Patients with hyperkalemia and electrocardiographic changes
ii.
Patients with [K] > 6.5 to 7 meq/L; some would not initiate such therapy until [K] is
7.0 meq/L in patients who have no clinical or ECG signs of hyperkalemia.
iii.
A lesser degree of hyperkalemia in patients with [K] that is rapidly increasing
Monitoring
A. Continuous cardiac monitoring and serial ECG are warranted in patients with
hyperkalemia who require rapidly acting therapies. The [K] should be measured at one
to two hours after initiation of therapy. The timing of further measurements is
determined by [K] and the response to therapy.
Calcium
A. Calcium directly antagonizes membrane actions of hyperkalemia, while hypocalcemia
increases cardiotoxicity of hyperkalemia. As discussed elsewhere, hyperkalemia-induced
depolarization of resting membrane potential leads to inactivation of sodium channels
B.

C.

D.

E.

and decreased membrane excitability.

The effect of IV 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.
Calcium can be given as either calcium gluconate or calcium chloride. Calcium chloride
contains three times the concentration of elemental calcium compared to calcium
gluconate (13.6 vs. 4.6 meq in 10 mL of 10% solution).
The usual dose of calcium gluconate is 1000 mg (10 mL of 10% solution) infused over 2
to 3 minutes, with constant cardiac monitoring. The usual dose of calcium chloride is 500
to 1000 mg (5 to 10 mL of 10% solution), also infused over 2 to 3 minutes, with constant
cardiac monitoring. The dose of either formulation can be repeated after 5 minutes if
ECG changes persist or recur.
Concentrated calcium infusions 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 small needle or
catheter in large vein. Calcium should not be given in bicarbonate-containing solutions,
which can lead to precipitation of calcium carbonate.

F.

5.

QRS complex or loss of P waves) even though hypercalcemia potentiates cardiotoxic

effects of digitalis. In such patients, a dilute solution can be administered slowly, infusing
10 mL of 10% calcium gluconate in 100 mL of 5% dextrose in water over 20 to 30
minutes, to avoid acute hypercalcemia. In patients with hyperkalemia due to digitalis
toxicity, the administration of digoxin-specific antibody fragments is preferred therapy.
Insulin with glucose
A. Insulin administration lowers [K] by driving potassium into cells, primarily by enhancing
activity of Na-K-ATPase pump in skeletal muscle. Glucose is usually given with insulin to
prevent development of hypoglycemia. However, insulin should be given alone if serum
glucose is 250 mg/dL. The serum glucose should be measured 1 hour after insulin.
B.

C.

6.

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

administered for same indications as in patients not treated with digitalis (widening of

One commonly used regimen for administering insulin and glucose is 10 units of RI in
500 mL of 10% dextrose, given over 60 minutes. Another regimen consists of bolus
injection of 10 U of RI, followed immediately by 50 mL of 50% dextrose (25 g of glucose).
This regimen may provide greater reduction in [K] since potassium-lowering effect is
greater at higher insulin concentrations attained with bolus therapy. However,
hypoglycemia occurs in up to 75% of patients treated with bolus regimen, typically 1
hour after infusion. To avoid this complication, we recommend subsequent infusion of
10% dextrose at 50 to 75 mL/hour and close monitoring of blood glucose levels.
The administration of glucose without insulin is not recommended since release of
endogenous insulin can be variable and the attained insulin levels are generally lower

with glucose infusion alone. Furthermore, in susceptible patients (primarily diabetic

patients with hyporeninemic hypoaldosteronism), hypertonic glucose in the absence of
insulin may acutely increase [K] by raising plasma osmolality, which promotes water and
potassium movement out of cells.
D. The effect of insulin begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts for
4 to 6 hours. In almost all patients, [K] drops by 0.5 to 1.2 meq/L. In particular, although
patients with renal failure are resistant to glucose-lowering effect of insulin, they are not
resistant to hypokalemic effect because Na-K-ATPase activity is still enhanced.
2 adrenergic agonists
A. Given the potential adverse effects described below, the authors and reviewers of this
topic believe that IV epinephrine should not be used in the treatment of hyperkalemia.

B.

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

C.

D.

7.

2-adrenergic agonists can be effective in acute treatment of hyperkalemia, lowering [K]

by 0.5 to 1.5 meq/L. Albuterol, which is relatively selective for2 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 IV infusion. In patients who cannot tolerate
nebulized albuterol and if IV therapy is not available, subcutaneous terbutaline is a
potential alternative. The peak effect is seen within 30 minutes with intravenous
infusion and at 90 minutes with nebulization.
Albuterol and insulin with glucose have additive effect, reducing serum potassium
concentration by approximately 1.2 to 1.5 meq/L. Thus, although albuterol should not be
used as monotherapy in hyperkalemic patients with ESRD, it can be added to insulin plus
glucose to maximize reduction in [K]. One problem in patients on maintenance

hemodialysis is that lowering [K] by driving potassium into the cells can diminish
subsequent potassium removal during dialysis session (from 50 to 29 meq in one report),
possibly leading to rebound hyperkalemia after dialysis.
E. Potential side effects of 2 agonists include mild tachycardia and 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.
Sodium bicarbonate
A. Raising systemic pH with sodium bicarbonate results in hydrogen ion release from cells
as part of buffering reaction. This change is accompanied by potassium movement into

B.

C.

cells to maintain electroneutrality. The use of bicarbonate for the treatment of

hyperkalemia was mainly based upon small uncontrolled clinical studies. However, in a
study that compared different potassium-lowering modalities in 10 patients undergoing
maintenance hemodialysis, bicarbonate infusion (isotonic or hypertonic) for up to 60
minutes had no effect on [K]. This lack of benefit was confirmed in several subsequent
studies of hemodialysis patients.
Given the limited efficacy, we do not recommend administration of sodium bicarbonate
as only therapy for acute management of hyperkalemia, even in patients with mild to
moderate metabolic acidosis. However, prolonged bicarbonate therapy appears to be
beneficial in patients with metabolic acidosis. In one series, for example, the
administration of isotonic sodium bicarbonate in constant infusion to patients with
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 4 and 6 hours; the serum bicarbonate increased to 28 meq/L at one hour and
30 meq/L at six hours.
In addition, acute or chronic bicarbonate (alkali) therapy may be warranted to treat
acidemia independent of hyperkalemia.

D.

8.

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

isotonic solution (150 meq in one liter of 5% dextrose in water over 2 to 4 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.
E. Over the long term, in patients with CKD, there are a variety of benefits from treating
metabolic acidosis, and alkali therapy is recommended to maintain near-normal serum
bicarbonate, independent of any effect on the serum potassium concentration.
Efficacy in ESRD
A. Most patients with persistent hyperkalemia have CKD (GFR < 30 mL/min). One report
found the following mean changes in [K] at 1 hour after the institution of the following
therapies in hyperkalemic patients requiring maintenance hemodialysis.
i.
ii.

A 0.85 meq/L reduction with insulin and glucose

A 0.3 meq/L reduction with epinephrine; a greater response, similar to that with
insulin and glucose, is typically seen with albuterol which has no alpha-adrenergic
activity
iii.
No change with sodium bicarbonate
iv.
A 1.3 meq/L reduction with hemodialysis
TREATMENT OF REVERSIBLE CAUSES
1. A variety of factors can contribute to or cause hyperkalemia. Thus, consideration should be
given to addressing such factors. These include reversible causes of impaired renal function,
such as hypovolemia, NSAID, urinary tract obstruction, and inhibitors of RAAS, each of
which can also directly cause hyperkalemia.
2. These abnormalities often cannot be corrected quickly, and their correction may not be
sufficient to induce large fall in serum potassium. Thus, when there is more than mild
hyperkalemia, modalities directed at potassium removal should not be delayed.
POTASSIUM REMOVAL
1. The effective modalities described above only transiently lower [K]. Thus, additional therapy
is typically required to remove excess potassium from 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.
2. The three available modalities for potassium removal are diuretics, cation exchange resin,
and dialysis.
3.

Loop or thiazide diuretics

A. Loop and thiazide diuretics increase potassium loss in 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 clinically important short-term kaliuretic response to diuretic therapy.

B.

4.

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. For patients with moderate hyperkalemia whose renal function is not
severely impaired, we suggest a trial of diuretics if otherwise appropriate (HTN or
hypervolemia). Among patients with hyperkalemia due to ACEI, many can be controlled
with low-potassium diet and diuretic therapy.
Cation exchange resins
A. The major available cation exchange resin is sodium polystyrene sulfonate. Although
"SPS" is often used as abbreviation for sodium polystyrene sulfonate, SPS is actually a
brand name for sodium polystyrene sulfonate in sorbitol.
B. Cation exchange resins, which are effective in lowering serum potassium after multiple
doses, are usually not effective immediately and do not appear to be more effective in
removing potassium from body than laxative therapy. Although uncommon, cation
exchange resins can produce severe side effects, particularly intestinal necrosis, which
may be fatal.
C. When to use cation exchange resins
i.
Clinicians are often faced with choice between using sodium polystyrene sulfonate
therapy and dialysis in patients with kidney disease and hyperkalemia. As will be
discussed below in further detail, cation exchange resins are usually not effective
after a single dose and may produce fatal side effects (particularly in postoperative
patients or those with ileus or bowel obstruction and in patients who have received
kidney transplant).
ii.

iii.

iv.

Given these concerns, dialysis is preferred treatment in patients with severe kidney
disease and potentially life-threatening hyperkalemia, particularly in patients who
have vascular access. In patients with less severe hyperkalemia, diuretic therapy,
low-potassium diet, and removal of potentially reversible causes (such as
discontinuation of ACEI) may be sufficient.
Thus, we suggest that sodium polystyrene sulfonate be used (in conjunction with
the rapidly acting transient therapies mentioned above) only in patient who meets
all of the following criteria.
1. Potentially life-threatening hyperkalemia
2. Dialysis is not readily available.
3. Other therapies to remove potassium (diuretics, rapid restoration of kidney
function) have failed or are not possible.
Sodium polystyrene sulfonate with or without sorbitol should not be given to the
following patients because they may be at high risk for intestinal necrosis.
1. Postoperative patients
2. Patients with ileus or who are receiving opiates
3. Patients with large or small bowel obstruction

v.

vi.

D.

Even if restoration of renal function or dialysis are not possible or immediately

available, sodium polystyrene sulfonate should not be given in these high-risk
settings; such patients can be managed with repeated doses of insulin and glucose
(or continuous infusions) until dialysis can be performed.
Despite modest efficacy and risk of catastrophic consequences, sodium polystyrene
sulfonate remains the most widely used treatment for hyperkalemia. In a six-month
single-center survey from ED, 1001 patients received sodium polystyrene sulfonate
in sorbitol, while only 188 received other therapies. Sodium polystyrene sulfonate is
also frequently used as chronic therapy to control hyperkalemia in patients with
CKD who do not have other indications for dialysis and whose hyperkalemia is not
controlled adequately with a low-potassium diet, diuretic therapy, and removal of
potentially reversible causes.

Mechanism of action
i.
In the gut, sodium polystyrene sulfonate takes up potassium (and calcium and
magnesium to lesser degrees) and releases sodium. Each gram of resin may bind as
much as 1 meq of potassium and release 1 to 2 meq of sodium. Thus, a potential
side effect is exacerbation of edema due to sodium retention. Calcium polystyrene
sulfonate, available outside the US, does not have significant sodium content.
ii.
The osmotic diarrhea induced by addition of sorbitol may also contribute to
potassium lowering. As an example, a carefully performed study in six patients on
maintenance hemodialysis found that 12-hour fecal potassium output with a single
dose of sodium polystyrene sulfonate in sorbitol was 31 meq; 19 meq was soluble,

and 12 meq was insoluble and presumably bound to the resin.

E. Administration and dose
i.
Sodium polystyrene sulfonate without or with sorbitol can be given orally and
sodium polystyrene sulfonate without sorbitol can be given as 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 4 to 6 hours as necessary.
Single doses are probably ineffective.
ii.
When given as enema, 50 g of sodium polystyrene sulfonate is mixed with 150 mL
of tap water (not sorbitol). After cleansing enema with tap water at body
temperature, resin emulsion should be administered at body temperature through
rubber tube placed at about 20 cm from the rectum with the tip well into the

iii.

sigmoid colon. The emulsion should be introduced by gravity and flushed with
additional 50 to 100 mL of non-sodium-containing fluid.
The emulsion should be kept in 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). The enema can be repeated every two to four hours, as
necessary.

F.

Sorbitol
i.
As discussed below, the occurrence of intestinal necrosis in some patients treated

ii.

iii.

iv.

with cation exchange resins led FDA to issue recommendation in September 2009
that SPS should no longer be administered in sorbitol. Thus, if cation exchange resin
is given, we prefer the preparation of sodium polystyrene
sulfonate without sorbitol (whenever possible). Sodium polystyrene sulfonate
without sorbitol comes in a powder form that must be reconstituted. The
suspension solution should not contain sorbitol.
Concurrent laxative therapy may be beneficial for the prevention and treatment of
constipation and possibly for enhanced gastrointestinal potassium loss. If given, the
preparation should not contain sorbitol, potassium, or cations such as magnesium
or calcium, which can compete with potassium for binding to the resin. In patients
with renal insufficiency, the laxative should also not contain phosphorus.
Preparations that fulfill all of these criteria include lactulose and some preparations
of polyethylene glycol 3350. Data demonstrating efficacy and safety in this setting
are not available. Certain polyethylene glycol electrolyte solutions that contain
potassium should not be used.
If SPS without sorbitol is not available, clinicians must consider whether treatment
with sodium polystyrene sulfonate in sorbitol is necessary. The low risk of intestinal
necrosis must be weighed against the delayed onset of efficacy with little evidence
of benefit in the first 12 hours.
If sodium polystyrene sulfonate in sorbitol is used, it should be given in a 33%

solution. It should not be given in a 70% sorbitol solution.

G. Efficacy of cation exchange resins
i.
Weak evidence suggests that SPS can lower serum potassium, usually after multiple
doses are given over 1 to 5 days; single doses are not very effective. However,
laxative therapy (sorbitol) may produce equivalent reduction in serum potassium.
ii.
In the largest published series, 30 patients with hyperkalemia due to AKI or CKD
were treated with 10 to 60 g per day of SPS orally or rectally. During the first 24
hours of therapy, the serum potassium decreased by average of 1 meq/L with oral
administration and 0.8 meq/L with rectal administration; 23 of 30 patients had a
decrease in serum potassium of at least 0.4 meq/L in the first 24 hours. However,
all patients received a low-potassium diet, and some received other therapies to
iii.

lower the serum potassium, such as insulin, glucose, and sodium bicarbonate.
Cation exchange resins do not appear to have superior efficacy as compared with
laxatives alone. As an example, a study of 10 patients with AKI and hyperkalemia
were given either SPS combined with sorbitol or sorbitol alone for five days. The
reduction in the serum potassium was larger in those given sorbitol alone (from 6.3
to 4.6 meq/L) than in those given sodium polystyrene sulfonate combined with
sorbitol (from 6.6 to 5.2 meq/L).

H.

Intestinal necrosis
i.
When SPS first became available, it was typically administered in water. However,

ii.

iii.

gastric and intestinal opacification caused by concretions of the crystalline resin

were described that could lead to intestinal obstruction, particularly when given
with aluminum hydroxide. As a result, it became increasingly popular to administer
sodium polystyrene sulfonate in a suspension of hypertonic sorbitol to promote an
osmotic diarrhea to avoid concretions and colonic impaction.
A major concern with SPS in sorbitol is the development of intestinal necrosis,
usually involving the colon and ileum, which is frequently a fatal complication. In
such cases, sodium polystyrene sulfonate crystals can often be detected in
pathological specimens, adherent to the injured mucosa. Sodium polystyrene
sulfonate in sorbitol can also injure the esophagus and stomach when given orally,
possibly resulting in manifestations such as bleeding and esophageal necrosis.
Other complications of sodium polystyrene sulfonate include hypocalcemia, volume
overload, and hypokalemia.
High-risk patients
1. The risk of intestinal necrosis may be greatest when SPS in sorbitol is given
within the first week after surgery, due to postoperative ileus and the
administration of opioids, which also increase the risk for ileus. In a series of
117 such patients, two (1.8%) developed intestinal necrosis. Additionally,
sodium polystyrene sulfonate should not be given to patients with obstructive
bowel disease.
2.

iv.

Despite the possible increase in risk in the postoperative setting, most cases of
intestinal necrosis associated with SPS in sorbitol are not related to surgery. As
an example, only two of eleven confirmed cases of intestinal necrosis
associated with sodium polystyrene sulfonate in sorbitol occurred in the
postoperative setting. Intestinal necrosis has also been reported after the
administration of sodium polystyrene sulfonate in sorbitol in renal transplant
recipients, although these patients may have had surgical ileus.
Presumed effect of sorbitol
1. The majority of cases of intestinal necrosis associated with SPS occurred when
the resin was administered with sorbitol. In addition, intestinal necrosis was
induced in a rat model by sorbitol alone or by sorbitol mixed with sodium

2.

polystyrene sulfonate, but not with sodium polystyrene sulfonate alone. Thus,
it was presumed that sorbitol was required for the intestinal injury.
As a result, the FDA issued a recommendation in September 2009 that SPS
should no longer be administered in sorbitol. Despite this, many hospitals and
pharmacies only stock sodium polystyrene sulfonate premixed in sorbitol.
Sodium polystyrene sulfonate alone is not always available and, when
available, comes as a powder that must be reconstituted.

v.

Intestinal necrosis in the absence of sorbitol

1. The association of sodium polystyrene sulfonate in sorbitol with intestinal
necrosis may be coincidental since sorbitol is so widely used in conjunction
with sodium polystyrene sulfonate. Multiple cases of intestinal necrosis with
sodium polystyrene sulfonate and similar cation exchange resins without
sorbitol have been reported. In addition, intestinal necrosis has been reported
in patients receiving sodium polystyrene sulfonate in a reduced concentration
(33%) of sorbitol. Thus, intestinal necrosis may be a complication of sodium
polystyrene sulfonate independent of sorbitol.

5.

Dialysis
A. Dialysis is indicated if measures listed above are insufficiently effective or hyperkalemia
is severe or is expected to increase rapidly as could occur with marked tissue breakdown,
leading to the release of large amounts of potassium from injured cells.
B. Hemodialysis is preferred, since the rate of potassium removal is many times faster than
with peritoneal dialysis. Hemodialysis can remove 25 to 50 meq of potassium per hour,
with variability based upon 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, and the potassium concentration of the dialysate.
C. Dialysate potassium concentration
i.
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.
D. Post-dialysis potassium rebound
i.
A rebound increase in serum potassium occurs after hemodialysis in all patients in
whom potassium is removed, since reduction in serum potassium during dialysis
create gradient for potassium movement out of cells. The magnitude of this effect
was evaluated in a study of 14 stable maintenance hemodialysis patients. The
average serum potassium concentrations at baseline, during hemodialysis, and up
to 6 hours after hemodialysis were 5.7, 3.6, and 5.0 meq/L. Thus, the serum
potassium should usually not be measured soon after completion of hemodialysis,
since the results are likely to be misleading.
ii.
The post-dialysis rebound after hemodialysis is more pronounced in patients
undergoing acute hemodialysis for hyperkalemia due to massive release of
potassium from injured cells (tumor lysis, rhabdomyolysis) and after regular
maintenance hemodialysis in patients with a high predialysis serum potassium
concentration.

iii.

Rapidly acting transient therapies given before dialysis, such as insulin with glucose
or albuterol, have two-fold effect: total potassium removal is reduced due to

lowering of the serum potassium concentration; and the potassium rebound is

greater because of 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.
iv.
Patients who have a large post-dialysis rebound may require daily dialysis or
continuous renal replacement therapy to avoid recurrent severe hyperkalemia.
END-STAGE RENAL DISEASE
1. Patients with ESRD requiring dialysis are often hyperkalemic to varying degrees prior to the
onset of the procedure. The potassium concentration in bath can be adjusted according to
the serum potassium concentration. In this nonemergent setting, the goal of therapy should
be gradual potassium removal rather than an acute reduction in the serum potassium
concentration to normal.
2. The management of the hyperkalemic patient with ESRD undergoing emergent surgery,
where there may not be time for preoperative dialysis, is discussed separately.
DRUG-INDUCED HYPERKALEMI
1. A variety of drugs can raise serum potassium, primarily by interfering with RAAS. Probably
most common are ACEI and ARB, aldosterone antagonists and other potassium sparing
diuretics (spironolactone, eplerenone, and amiloride), digitalis, and NSAID (table 3).
2. These drugs should be discontinued or the dose reduced at least temporarily until the
hyperkalemia is controlled.
PREVENTION
1. There are several measures that can help to prevent hyperkalemia in patients with CKD,
particularly those with ESRD. In addition to low-potassium diet, the following modalities have
been effective in stable maintenance hemodialysis patients.
A. Avoid episodes of fasting, which can increase potassium movement out of the cells due,
at least in part, to reduced insulin secretion. In a study of 10 stable patients on
maintenance hemodialysis who did not have DM, fasting for 18 hours led to mean 0.6
meq/L rise in serum potassium, which was completely prevented when the protocol was
repeated with the administration of low dose insulin with dextrose. Thus, non-diabetic
patients with ESRD who are undergoing elective surgery should, if they are in the
B.

hospital, receive parenteral glucose-containing solutions when fasting overnight.

Avoid drugs that raise serum potassium. These include inhibitors of RAAS, such as ACEI,
ARB, direct renin inhibitors, aldosterone antagonists, and nonselective B (propranolol).
1-selective blockers such as metoprolol and atenolol are much less likely to cause
hyperkalemia.

2.

Patients with CKD or HF are often treated with RAAS inhibitors. A variety of preventive
measures can diminish the risk of hyperkalemia.
A.
B.
C.
D.

E.
F.

Close monitoring of serum potassium and eGFR, particularly after changes in RAAS
inhibitor therapy.
Dietary restriction of potassium.
Avoidance or discontinuation of other drugs that impair potassium excretion (NSAID).
The utilization of low initial doses and evidence-based final doses of RAAS inhibitors for
specific indications (HF, proteinuric CKD). The dose should be reduced with moderate
hyperkalemia (serum potassium 5.5 meq/L) and therapy discontinued if serum
potassium rises > 5.5 meq/L unless serum potassium can be reduced by diuretic therapy.
The use of thiazide or loop diuretics whenever otherwise indicated.
There are no good data on chronic efficacy of oral alkali therapy (sodium bicarbonate or

sodium citrate) for 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 recommended to maintain
near-normal serum bicarbonate, independent of any effect on the serum potassium
concentration.
SUMMARY AND RECOMMENDATIONS
1. Hyperkalemia is most often due to impaired urinary potassium excretion due to acute or
chronic kidney disease and/or disorders or drugs that inhibit the
renin-angiotensin-aldosterone axis. Less commonly, redistributive hyperkalemia results from
the movement of potassium out of the cells, even though the total body potassium may be
2.

3.

reduced. The main cause of redistributive hyperkalemia is uncontrolled hyperglycemia.

The urgency of treatment of hyperkalemia varies with the cause and the presence or absence
of the symptoms and signs associated with hyperkalemia. Marked tissue breakdown can be
associated with rapid and substantial elevations in serum potassium. As a result, aggressive
therapy to remove potassium is warranted in such patients even if there is only a modest
elevation in serum potassium.
Rapidly acting therapies for acute hyperkalemia that may be used include the administration
of calcium, insulin with glucose, and, in selected patients, -2-adrenergic agonists, and
sodium bicarbonate. These therapies are primarily used among patients with hyperkalemia
and electrocardiographic changes; those with a serum potassium greater than 6.5 to 7.0
meq/L; or those with a lower serum potassium that is rapidly increasing due to marked tissue
breakdown.
A. We recommend calcium infusion in addition to other therapies in patients who have
severe manifestations of hyperkalemia such as widening of the QRS complex or loss of P
waves, in whom it would be potentially dangerous to wait the 30 to 60 minutes for
insulin and glucose to act.

B.

C.

4.

5.

6.
7.

8.

We recommend the administration of insulin in patients with a serum potassium

concentration greater than 6.5 to 7.0 meq/L or less severe hyperkalemia associated with
electrocardiographic changes or lower serum potassium that is rapidly increasing.
Glucose is usually given with insulin to prevent the development of hypoglycemia.
However, insulin should be given alone if serum glucose is 250 mg/dL. A commonly
used regimen for administering insulin and glucose is 10 units of regular insulin in 500
mL of 10% dextrose, given over 60 minutes. Another regimen consists of a bolus
injection of 10 units of regular insulin, followed immediately by 50 mL of 50% dextrose
(25 g of glucose). To avoid hypoglycemia, a subsequent infusion of 10% dextrose at 50 to
75 mL/hour should be administered. With either regimen, the serum glucose should be
measured one hour after the administration of insulin.
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.
D. Sodium bicarbonate is not indicated as single agent for acute management of
hyperkalemia, but may be given for treatment of significant metabolic acidosis. In such
patients, we prefer administration of isotonic solution (150 meq in 1 liter of 5% dextrose
in water over two to four hours) providing the patient can tolerate the volume load.
Reversible causes of impaired renal function should be addressed in all patients with
hyperkalemia. Reversible causes include hypovolemia, NSAID, urinary tract obstruction, and
inhibitors of RAAS, which can also directly cause hyperkalemia.
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.
A. Diuretics (which are primarily used for chronic therapy)
B. Cation exchange resins
C. Dialysis
Although data documenting their effectiveness are lacking, we suggest a trial of diuretics for
patients with moderate hyperkalemia whose renal function is not severely impaired.
Cation exchange resins (sodium polystyrene sulfonate) can lower the potassium
concentration and are frequently used in clinical practice. The usual dose is 15 to 30 g, which
can be repeated every four to six hours. However, cation exchange resins are usually not
effective after a single dose and may produce fatal side effects (especially intestinal necrosis).
If is given, we prefer the preparation of sodium polystyrene sulfonate without sorbitol.
However, the following hyperkalemic patients should not receive cation exchange resins
(sodium polystyrene sulfonate); repetition of rapidly acting transient therapies (such as with
repeated doses of insulin and glucose) is preferred in such patients until dialysis is available.
A. Postoperative patients
B. Patients with ileus or who are receiving opiates
C. Patients with large or small bowel obstruction

9.

In other hyperkalemic patients who meet all of the following criteria, we suggest therapy
with a cation exchange resin rather than with repeated doses of insulin and glucose.
A.
B.
C.

Potentially life-threatening hyperkalemia

Dialysis is not readily available.
Other therapies to remove potassium (diuretics, rapid restoration of kidney function)
have failed or are not possible.
10. Dialysis is indicated if measures listed above are insufficiently effective or hyperkalemia is
severe or is expected to increase rapidly as could occur with marked tissue breakdown,
leading to the release of large amounts of potassium from injured muscle. Hemodialysis is
preferred since the rate of potassium removal is many times faster than with peritoneal
dialysis.