Hyperkalemia is defined as a serum potassium concentration greater than approximately 5.0-5.5 mEq/L in adults; the range in infants and children is age-dependent. Levels higher than 7 mEq/L can lead to significant hemodynamic and neurologic consequences, whereas levels exceeding 8.5 mEq/L can cause respiratory paralysis or cardiac arrest and can quickly be fatal. See the image below.
View Image
Widened QRS complexes in patient whose serum potassium level was 7.8 mEq/L.
Signs and symptoms
Many individuals with hyperkalemia are asymptomatic. When present, symptoms are nonspecific and predominantly related to muscular or cardiac function. Weakness and fatigue are the most common complaints. Occasionally, patients may report the following:
Frank muscle paralysis
Dyspnea
Palpitations
Chest pain
Nausea or vomiting
Paresthesias
In general, the results of the physical examination alone do not alert the physician to the diagnosis of hyperkalemia, except when severe bradycardia is present or muscle tenderness accompanies muscle weakness, suggesting rhabdomyolysis. Examination findings in patients with hyperkalemia include the following:
Vital signs usually normal, except occasionally in bradycardia due to heart block or tachypnea due to respiratory muscle weakness
Muscle weakness and flaccid paralysis
Depressed or absent deep tendon reflexes
When hyperkalemia is discovered, investigate potential pathophysiologic mechanisms. Hyperkalemia can result from any of the following, which often occur in combination:
Excessive intake
Decreased excretion
A shift of potassium from the intracellular to the extracellular space
See Clinical Presentation for more detail.
Diagnosis
In a patient who does not have a predisposition to hyperkalemia, repeat the blood test before taking any actions to bring down the potassium level, unless ECG changes are present. Other tests include the following:
ECG
Urine potassium, sodium, and osmolality
Complete blood count (CBC)
Metabolic profile
If the BUN and serum creatinine levels suggest renal insufficiency, using the MDRD or CKD-EPI equation to determine the estimated glomerular filtration rate (eGFR) is recommended.[1] Chronic kidney disease alone generally will not cause hyperkalemia until the eGFR is less than 20-25 mL/min.
Depending on the clinical findings and the results of the above laboratory work, the following may be indicated:
Glucose level - In patients with known or suspected diabetes mellitus
Digoxin level - If the patient is on a digitalis medication
Arterial or venous blood gas - If acidosis is suspected
Urinalysis - If signs of renal insufficiency without an already known cause are present (to look for evidence of glomerulonephritis)
Serum cortisol and aldosterone levels - To check for mineralocorticoid deficiency when other causes are eliminated
Serum uric acid and phosphorus tests - For tumor lysis syndrome
Serum creatinine phosphokinase (CPK) and calcium measurements - For rhabdomyolysis
Urine myoglobin test - For crush injury or rhabdomyolysis; suspect if urinalysis reveals blood in the urine but no red blood cells are seen on urine microscopy
ECG
Vital for assessing the physiologic significance of the hyperkalemia
ECG findings generally correlate with the potassium level, but potentially life-threatening arrhythmias can occur without warning at almost any level of hyperkalemia
In patients with organic heart disease and an abnormal baseline ECG, bradycardia may be the only new ECG abnormality
ECG changes have a sequential progression, which roughly correlate with the potassium level, but with the caveats mentioned above[2]
Early ECG changes of hyperkalemia, typically seen at a serum potassium level of 5.5-6.5 mEq/L, include the following:
Tall, peaked T waves with a narrow base, best seen in precordial leads[3]
Shortened QT interval
ST-segment depression
At a serum potassium level of 6.5-8.0 mEq/L, the ECG typically shows the following:
Peaked T waves
Prolonged PR interval
Decreased or disappearing P wave
Widening of the QRS
Amplified R wave
At a serum potassium level higher than 8.0 mEq/L, the ECG shows the following:
Absence of P waves
Progressive QRS widening
Intraventricular/fascicular/bundle branch blocks
The progressively widened QRS eventually merges with the T wave, forming a sine wave pattern. Ventricular fibrillation or asystole follows.
See Workup for more detail.
Management
The aggressiveness of therapy is directly related to the rapidity with which hyperkalemia has developed, the absolute level of hyperkalemia, and the evidence of toxicity. The faster the rise of potassium, the higher the level, and the stronger the evidence of cardiotoxicity, the more aggressive therapy should be.
If the patient has only a moderate elevation in potassium level and no ECG abnormalities, treatment is as follows:
Increase potassium excretion using a cation exchange resin or diuretics
Correct the source of excess potassium (eg, increased intake or inhibited excretion)
In patients with severe hyperkalemia, treatment is as follows:
IV calcium to ameliorate cardiac toxicity, if present
Identify and remove sources of potassium intake
IV glucose and insulin infusion to enhance potassium uptake by cells
Correct severe metabolic acidosis with sodium bicarbonate
Consider beta-adrenergic agonist therapy (eg, nebulized albuterol, 10 mg, administered by a respiratory therapist); preferred over alkali therapy in patients with renal failure
Increase potassium excretion by administering diuretics or gastrointestinal cation-exchange medications
Emergency dialysis for patients with potentially lethal hyperkalemia that is unresponsive to more conservative measures or with complete renal failure
Medications for increasing potassium excretion include the following:
IV saline and a loop diuretic (eg, furosemide), in patients with normal renal function
An aldosterone analogue, such as 9-alpha fluorohydrocortisone acetate (Florinef), in patients with hyporeninemia or hypoaldosteronism or solid organ transplant patients with chronic hyperkalemia from calcineurin inhibitor use
Potassiuim binders include cation exchange resins such as sodium polystyrene sulfonate (SPS; Kayexalate), patiromer, or sodium zirconium cyclosilicate (Lokelma); an SPS retention enema may be used for hyperkalemic emergencies, oral products have slower onset of action, but may be considered for patients with advanced renal failure who are not yet on dialysis or are transplant candidates
Surgery
Surgery is typically unnecessary, but the following scenarios may involve surgical intervention:
Patients with metabolic acidosis and consequent hyperkalemia due to ischemic gut: Exploration required
Patients with hyperkalemia due to rhabdomyolysis: Surgical decompression of swollen ischemic muscle compartments may be needed
Patients without end-stage renal disease who require hemodialysis for control of hyperkalemia: Placement of a hemodialysis catheter for emergent dialysis needed[4]
Hyperkalemia is defined as a serum potassium concentration higher than the upper limit of the normal range; the range in infants and children is age-dependent, whereas the range for adults is approximately 3.5-5.5 mEq/L. The upper limit may be considerably higher in young or premature infants, as high as 6.5 mEq/L.[5] Degrees of hyperkalemia are generally defined as follows (however, note that not all sources agree on these levels)[6] :
5.5-6.0 mEq/L – Mild
6.1-7.0 mEq/L – Moderate
≥7.0 mEq/L – Severe
Levels higher than 7 mEq/L can lead to significant hemodynamic and neurologic consequences. Levels exceeding 8.5 mEq/L can cause respiratory paralysis or cardiac arrest and can quickly be fatal.
Because of a paucity of distinctive signs and symptoms, hyperkalemia can be difficult to diagnose. Indeed, it is frequently discovered as an incidental laboratory finding. The physician must be quick to consider hyperkalemia in patients who are at risk for this disease process. (See Etiology.) However, any single laboratory study demonstrating hyperkalemia must be repeated to confirm the diagnosis, especially if the patient has no changes on electrocardiography (ECG).
Because hyperkalemia can lead to sudden death from cardiac arrhythmias, any suggestion of hyperkalemia requires an immediate ECG to ascertain whether ECG signs of electrolyte imbalance are present (see Workup). Continuous ECG monitoring is essential if hyperkalemia is confirmed. Other testing is directed toward uncovering the condition or conditions that led to the hyperkalemia (see Workup).
The aggressiveness of therapy for hyperkalemia is directly related to the rapidity with which the condition has developed, the absolute level of serum potassium, and the evidence of toxicity. The faster the rise of the potassium level, the higher it has reached, and the greater the evidence of cardiotoxicity, the more aggressive therapy should be.
In severe cases, treatment focuses on immediate stabilization of the myocardial cell membrane, rapid shifting of potassium to the intracellular space, and total body potassium elimination. In addition, all sources of exogenous potassium should be immediately discontinued. (See Treatment.)
Potassium is the primary intracellular cation; 95-98% of the total body potassium is found in the intracellular space, primarily in muscle. Total body potassium stores amount to approximately 50 mEq/kg (3500 mEq in a 70-kg person).
Normal homeostatic mechanisms precisely maintain the serum potassium level within a narrow range (3.5-5.0 mEq/L). The primary mechanisms for maintaining this balance are the buffering of extracellular potassium against a large intracellular potassium pool (via the sodium-potassium pump), which provides minute-to-minute control, and urinary excretion of potassium, which determines total body potassium balance.
Potassium is obtained through the diet. Common potassium-rich foods include meats, beans, tomatoes, potatoes, and fruits such as bananas. Gastrointestinal (GI) absorption is complete, resulting in daily excess intake of about 1 mEq/kg (60-100 mEq).
Under normal conditions, approximately 90% of potassium excretion occurs in the urine, with less than 10% excreted through sweat or stool. Within the kidneys, potassium excretion occurs mostly in the principal cells of the cortical collecting duct (CCD). Urinary potassium excretion depends on adequate luminal sodium delivery to the distal convoluted tubule (DCT) and the CCD, as well as the effect of aldosterone and other adrenal corticosteroids with mineralocorticoid activity.
Renal factors in potassium homeostasis
Sodium reabsorption through epithelial sodium channels (ENaC) located on the apical membrane of cortical collecting tubule cells is driven by aldosterone and generates a negative electrical potential in the tubular lumen, driving the secretion of potassium at this site through the renal outer medullary potassium (ROMK) channels. Aldosterone also regulates sodium transport in the thick ascending limb of the loop of Henle, the DCT, and the connecting tubule.
A family of signaling molecules, the WNK (with no K [lysine]) kinases, plays a critical role in the regulation of sodium and potassium transport in the distal nephron.[7] The WNK kinases are suspected of playing a role in the pathogenesis of several forms of hypertension.[4, 8]
WNK1 and WNK4 regulate the expression and function of the NaCl cotransporter and ROMK in the distal tubule. Increased WNK4 activity results in decreased NaCl cotransporter expression, permitting greater delivery of sodium to the cortical collecting tubule, thus facilitating potassium secretion. Conversely, lesser WNK4 activity results in increased NaCl cotransporter expression, diminishing distal sodium delivery, thus limiting cortical collecting tubule potassium secretion.[9, 10]
Renal potassium excretion is increased by the following:
Aldosterone
WNK1 and WNK4
High sodium delivery to the distal tubule (eg, diuretics)
High urine flow (eg, osmotic diuresis)
High serum potassium level
Delivery of negatively charged ions to the distal tubule (eg, bicarbonate)
Renal potassium excretion is decreased by the following:
Absence, or very low levels, of aldosterone
WNK1 and WNK4 mutations
Low sodium delivery to the distal tubule
Low urine flow
Low serum potassium level
Kidney injury
Kidneys adapt to acute and chronic alterations in potassium intake. When potassium intake is chronically high, potassium excretion also is increased. Even in the absence of potassium intake, however, obligatory renal losses amount to 10-15 mEq/day. Thus, chronic losses occur in the absence of any ingested potassium.
In chronic kidney disease, renal adaptive mechanisms allow the kidneys to maintain potassium homeostasis until the glomerular filtration rate (GFR) decreases to less than 15-20 mL/min. Additionally, in the presence of renal failure, the proportion of potassium excreted through the gut is thought to increase, though evidence for this compensatory mechanism has been elusive.
The colon is the major site of gut regulation of potassium excretion. Therefore, potassium levels can remain relatively normal under stable conditions, even with advanced renal insufficiency. However, as renal function worsens, the kidneys may not be capable of handling an acute potassium load. An excess of only 100-200 mEq will increase the serum potassium concentration by about 1 mEq/L.[11]
Potassium distribution and serum potassium levels
Potassium is predominantly an intracellular cation; thus, serum potassium levels do not always accurately reflect total body potassium stores. Serum potassium levels are determined by the shift of potassium between intracellular and extracellular fluid compartments, as well as by total-body potassium homeostasis.
Several factors regulate the distribution of potassium between the intracellular and extracellular spaces, including glucoregulatory hormones, adrenergic stimuli, and pH. Insulin enhances potassium entry into cells, whereas glucagon impairs it. Beta-adrenergic agonists enhance potassium entry into cells, whereas beta-blockers and alpha-adrenergic agonists inhibit it.
Alkalosis enhances potassium entry into cells. Acidosis causes a shift of potassium from intracellular space into extracellular space. Inorganic or mineral acid acidoses are more likely to cause a shift of potassium out of the cells than organic acidosis is.
In addition, an acute increase in osmolality, such as may result from hyperglycemia, causes potassium to exit from cells. Acute cell-tissue breakdown (eg, hemolysis or rhabdomyolysis) releases potassium into the extracellular space.
The 2 sets of regulatory factors—those that regulate total-body homeostasis and those that regulate distribution of potassium between intracellular and extracellular spaces—meld to create smooth control of potassium levels throughout the day. Thus, serum concentrations can remain stable even in the face of acute intake or loss of potassium.
For example, although a high-potassium meal might contain enough potassium to raise the serum potassium acutely to lethal levels if the potassium remained in the extracellular space, Na+ -K+ -ATPase rapidly takes up the potassium into cells, thus preventing the development of hyperkalemia. Adrenergic stimulation and insulin are important in maintaining the activity of Na+ -K+ -ATPase. The excess potassium then can be excreted by the kidneys, allowing serum potassium levels to return to normal.
Recent studies point toward a gastrointestinal-renal signal that is aldosterone-independent and causes enhanced renal potassium excretion after a meal. The mechanisms have not been fully determined.[12]
This integrated regulatory process is manifested in the diurnal rhythm for renal potassium excretion. The highest excretion occurs at midday, approximately 18 hours after peak potassium ingestion at the evening meal.[13]
Pathogenetic mechanisms
Hyperkalemia can result from any of the following:
Excessive intake of potassium
Decreased excretion of potassium
A shift of potassium from the intracellular to the extracellular space
In many cases a combination of these factors is involved. For example, a person with a GFR of less than 45 mL/min who consistently eats large amounts of high-potassium foods and is taking a medication that blocks the rennin-angiotensin-aldosterone system is at very high risk for hyperkalemia due to limitations in renal excretion of potassium in the face of high intake.
A person with diabetes mellitus who has hyporeninemic hypoaldosteronism associated with diabetic nephropathy is at high risk for hyperkalemia due to a diminished ability to shift potassium into the intracellular space (insulin deficiency) and impaired renal excretion (aldosterone deficiency). A third circumstance is acute kidney injury from rhabdomyolysis or tumor lysis syndrome, in which hyperkalemia results from impaired renal excretion in addition to the release of large amounts of potassium from intracellular to extracellular fluid compartments.
Excessive intake
Excessive potassium intake alone is a very uncommon cause of hyperkalemia in anyone with an estimated GFR higher than 60 mL/min. The mechanisms for shifting potassium intracellularly and for renal excretion allow a person with normal potassium homeostatic mechanisms to ingest very high quantities of potassium. Even parenteral administration of as much as 60 mEq/hr for several hours creates only a minimal increase in serum potassium concentration in healthy individuals.
The most common source of increased potassium intake is intravenous (IV) or oral potassium supplementation. Packed red blood cells (PRBCs) may also carry high concentrations of potassium that can lead to hyperkalemia during PRBC transfusion.[14]
Decreased excretion
Decreased excretion of potassium, especially when coupled with excessive intake, is the most common cause of hyperkalemia. The most common causes of decreased renal potassium excretion include the following:
Renal failure (most common)[15]
Medications that interfere with potassium excretion (eg, potassium-sparing diuretics, angiotensin-converting enzyme [ACE] inhibitors,[16, 17, 18, 19] and nonsteroidal anti-inflammatory drugs [NSAIDs])
Reduced aldosterone production
Impaired responsiveness of the distal tubule to the action of aldosterone (eg, type IV renal tubular acidosis observed with diabetes mellitus, sickle cell disease, or chronic partial urinary tract obstruction)[20, 21]
Primary adrenal disease (eg, Addison disease or salt-wasting forms of congenital adrenal hyperplasia)
Hyporeninemic hypoaldosteronism or renal tubular disease (pseudohypoaldosteronism I[22] or II)
Shift from intracellular to extracellular space
A number of factors can influence the shift of potassium from the intracellular to the extracellular space (see table below). By itself, this mechanism is a relatively uncommon cause of hyperkalemia, but it can exacerbate hyperkalemia produced by high intake or impaired renal excretion of potassium. A common scenario is that insulin deficiency or acute acidosis produces mild-to-moderate impairment of intracellular shifting of potassium.
Clinical situations in which this mechanism is the major cause of hyperkalemia include the following:
Hyperosmolality
Tissue breakdown (eg, rhabdomyolysis, tumor lysis syndrome, or massive hemolysis)
Propofol (“propofol infusion syndrome”)[23]
Toxins (digitalis intoxication or fluoride intoxication)
Succinylcholine (depolarizes the cell membrane and thus permits potassium to leave the cells[24, 25, 26] )
Beta-adrenergic blockade
Strenuous or prolonged exercise
Malignant hyperthermia
Hyperkalemic periodic paralysis
Hyperkalemia may also be caused by IV administration of epsilon aminocaproic acid (EACA), a synthetic amino acid. EACA has been found to cause hyperkalemia in studies conducted in dogs. The mechanism of action is presumed to be a structural similarity between EACA and arginine and lysine. These latter amino acids enter the muscle cell in exchange for potassium, thereby leading to an increase in extracellular potassium.[27, 28]
Cardiac and skeletal muscle effects
High levels of potassium cause abnormal heart and skeletal muscle function by lowering cell-resting action potential and preventing repolarization, leading to muscle paralysis. Classic ECG findings begin with tenting of the T wave, followed by lengthening and eventual disappearance of the P wave and widening of the QRS complex.[29] However, varying degrees of heart block are also common.
Just before the heart stops, the QRS and T wave merge to form a sinusoidal wave.
Hyperkalemia can result from increased potassium intake, decreased potassium excretion, or a shift of potassium from the intracellular to the extracellular space. The most common causes involve decreased excretion. Alone, excessive intake or an extracellular shift is distinctly uncommon. Often, several disorders are present simultaneously.
Increased potassium intake
Alone, increased intake of potassium is a rare cause of hyperkalemia, because the mechanisms for renal excretion and intracellular disposition are very efficient. In general, a relatively high potassium intake contributes to hyperkalemia in individuals who have impaired renal excretion or intracellular-to-extracellular shift.
Increased intake may result from the following:
High-potassium, low-sodium diets
Ingestion of potassium supplements – Ingested amounts would have to be massive to be the sole cause of hyperkalemia, but even relatively small amounts can produce hyperkalemia in a patient with impaired renal excretion
High concentrations of potassium in IV fluid preparations (eg, total parenteral nutrition formulas)
Dietary salt substitutes – Several “no-salt” or “low-salt” substitutes contain about 10-12 mEq of potassium per gram of salt and can be dangerous, especially with diminished renal function
Penicillin G potassium therapy
PRBC transfusion (risk peaks at 2-3 weeks of cell storage)
Cardioplegia solutions – These contain 20-30 mmol/L of potassium chloride
Decreased potassium excretion
Almost all patients who present with persistent hyperkalemia have impaired renal excretion of potassium. Mild degrees of renal failure generally do not result in resting hyperkalemia, because of compensation by adaptive mechanisms in the kidneys and GI tract. However, once the GFR falls below 15-20 mL/min, significant hyperkalemia can occur, even in the absence of an abnormally large potassium load. The simple lack of nephron mass prevents normal potassium homeostasis.
Other mechanisms, such as drug effects or renal tubular acidosis, can decrease renal potassium excretion and cause hyperkalemia even in individuals with normal or only mildly decreased renal function. Two other causes of decreased excretion of potassium are reduced distal sodium delivery and reduced tubular fluid flow rate.
Medications that can decrease potassium excretion include the following:
Disorders that can cause type IV renal tubular acidosis, resulting in hyperkalemia, include the following:
Diabetes mellitus
Sickle cell disease or trait
Lower urinary tract obstruction
Adrenal insufficiency
Primary Addison syndrome due to autoimmune disease, tuberculosis, or infarct
Enzyme deficiencies
Genetic disorders (see below)
Shift of potassium into extracellular space
Like increased intake, this is rarely the sole cause of hyperkalemia, because the mechanisms for renal excretion are very efficient. However, the inability to transport potassium intracellularly exacerbates hyperkalemia in individuals who have impaired renal excretion.
Factors that can shift potassium into the extracellular space include the following:
Metabolic acidosis
Beta-adrenergic blockade[30, 31]
Acute tubular necrosis
Electrical burns
Thermal burns
Cell depolarization
Head trauma
Digitalis toxicity
Fluoride toxicity[32]
Cyclosporine[33]
Methotrexate[34]
Propofol infusion syndrome
Rhabdomyolysis
Tumor lysis syndrome
Succinylcholine[25]
Hypertonicity may lead to hyperkalemia by the following 2 mechanisms:
Loss of intracellular water, resulting in an increased intracellular potassium concentration, favoring a gradient for potassium to move out of the cells
As water exits the cells, “solvent drag,” which sweeps potassium along
The most common cause of hyperosmolality is hyperglycemia in uncontrolled diabetes mellitus. Other conditions with hypertonicity are hypernatremia, hypertonic mannitol, and high-osmolarity contrast media..
Aldosterone deficiency is somewhat controversial as a cause of hyperkalemia. There is some evidence that long-term aldosterone deficiency impairs cell potassium uptake.
Toad venom, which is used in traditional Chinese medicine and in folk medicine in southeastern Asia, contains cardiac glycosides whose structure and biochemical activity are similar to those of digitalis. These cause hyperkalemia by binding to the alpha subunit of Na+ -K+ -ATPase and thus inhibiting reuptake of potassium from the extracellular space.[35]
Toad venom is prepared from dried secretions, typically from the Asiatic toad (Bufo gargarizans). In addition being an ingredient in Chinese medications (eg, Chan Su, Lu-Shen Wan), toad venom has also turned up in purported aphrodisiacs. Digoxin Fab fragments have been used to treat toad venom poisoning.[36]
Genetic disorders
Genetic disorders that can result in hyperkalemia include the following:
Glomerulopathy with fibronectin deposits (GFND)
Disorders of steroid metabolism and mineralocorticoid receptors[36, 37]
Congenital hypoaldosteronism
Pseudohypoaldosteronism
Disorders of chloride homeostasis
Nephronophthisis
Hyperkalemic periodic paralysis (HYPP)
Glomerulopathy with fibronectin deposits
GFND is a genetically heterogeneous autosomal dominant disorder which manifests as proteinuria, hypertension, type IV renal tubular acidosis. It eventually leads to end-stage renal failure, in the second to fifth decade of life. Type 1 GFND maps to chromosome 1q32, but the gene is unknown at this time. Type 2 GFND is caused by mutations in the FN1 gene located on chromosome 2q34.
Disorders of steroid metabolism and mineralocorticoid receptors
21-hydroxylase deficiency in its classic form and aldosterone synthase deficiency result in hyperkalemia due to low aldosterone levels. 11-Beta hydroxylase deficiency, 3-beta hydroxysteroid dehydrogenase deficiency, and 17 alpha-hydroxylase/17,20-lyase deficiency are generally not characterized by the development of hyperkalemia.
Congenital hypoaldosteronism
Congenital hypoaldosteronism is caused by mutations in the CYP11B2 gene, which encodes the type II corticosterone methyloxidase enzyme. It is inherited in an autosomal recessive manner. Patients with this disorder have decreased aldosterone and salt wasting. They will have an increased serum ratio of 18-hydroxycorticosterone to aldosterone.
Pseudohypoaldosteronism
Type I pseudohypoaldosteronism (PHAI) can be caused by an inactivating mutation of 1 of 3 encoding subunits of the epithelial sodium channel (SCNN1A, SCNN1G, or SCNN1B). PHAI is inherited in an autosomal recessive manner. These mutations result in impaired potassium secretion due to impaired sodium reabsorption in the distal tubule.[38]
PHAI tends to be most severe in the neonatal period, causing renal salt wasting and respiratory tract infections. Sweat, stool, and saliva have high sodium concentrations. Sometimes this disorder can be mistaken for cystic fibrosis.
Another form of PHAI is caused by mutations in the NR3C2 gene and is inherited in an autosomal dominant manner. Patients with this disorder may present in the neonatal period with renal salt wasting and hyperkalemic acidosis similar to those seen in the autosomal recessive form. Patients with this form of PHAI generally improve with age and are typically asymptomatic in adulthood.[39]
Gordon syndrome, or pseudohypoaldosteronism type II (PHAII), characterized by hyperkalemia and hypertension, is caused by mutations in several genes. The following 5 loci are known to be associated with PHAII:
PHA2A has been mapped to chromosome 1q31-q42, but no gene is known at the present time
PHA2B is caused by mutations in the WNK4 gene on chromosome 17q21
PHA2C is caused by mutations in the WNK1 gene on chromosome 12p13
PHA2D is caused by mutations in the KLHL3 gene on chromosome5q31
PHA2E is caused by mutations in the CUL3 gene on chromosome 2q36
The genes causing this disorder code for protein kinases that are localized to the distal tubule and that regulate ion transport in this nephron segment. WNK4 appears to have several roles in regulating sodium, potassium, and chloride transport through transcellular and paracellular pathways.[40] Interestingly, PHAII from mutations in WNK1 is significantly less severe than PHAII from mutations in WNK4 or KLHL3, whereas PHAII from mutations in CUL3 is more severe.[41] All forms of PHII generally respond to treatment with thiazide diuretics.
Disorders of chloride homeostasis
Disorders of chloride homeostasis can also result in hyperkalemia. Isolated hyperchlorhidrosis is caused by mutations in the CA12 gene, and is inherited in an autosomal recessive manner. This disorder can cause excessive salt wasting in sweat, which can result in severe hyponatremic dehydration and hyperkalemia.[42]
Nephronophthisis
Nephronophthisis is characterized by enlargement of the kidneys, inflammatory portal fibrosis of the liver, and variable development of end-stage renal disease (ESRD). Patients with the infantile form of this disease generally reach ESRD before the age of 2 years. Patients with the juvenile form reach ESRD at a median age of 13 years. Patients with other forms of the disease have variable natural history.
Ultimately, this disorder causes a progressive interstitial fibrosis and tubulopathy. Routine laboratory evaluation will show increased creatinine and potassium.
Hyperkalemic periodic paralysis
HYPP is caused by mutations in the SCN4A gene and is inherited in an autosomal dominant manner. During attacks (which can be precipitated by administration of potassium), individuals with HYPP have flaccid generalized weakness and increased serum potassium levels. In addition, patients with HYPP can also have myotonia, which is not typically a feature of hypokalemic periodic paralysis (HOKPP). A number of similar disorders involving myotonia or muscular weakness are allelic to HYPP.[43]
Diabetes mellitus
Patients with diabetes constitute a unique high-risk group for hyperkalemia, in that they develop defects in all aspects of potassium metabolism.[16, 17] The typical healthy diabetic diet often is high in potassium and low in sodium. Diabetic persons frequently have underlying renal disease and often develop hyporeninemic hypoaldosteronism (ie, decreased aldosterone secondary to suppressed renin levels), impairing renal excretion of potassium.[20, 21]
Many patients with diabetes are placed on ACE inhibitor or ARB therapy for treatment of hypertension or diabetic nephropathy, exacerbating the defect in potassium excretion. Finally, persons with diabetes have insulin deficiency or resistance to insulin action, limiting their ability to shift potassium intracellularly.
Hyperkalemia, defined as a serum potassium concentration greater than 5.0–5.3 mEq/L, is rare in a general population of healthy individuals. In hospitalized patients, the incidence of hyperkalemia has ranged from 1% to 10%, depending on how the condition is defined. In hospitalized patients, drugs are implicated in the development of hyperkalemia in as many as 75% of cases. Decreased renal function,[15] genitourinary disease, cancer, severe diabetes, and polypharmacy may also predispose to hyperkalemia.
The incidence of hyperkalemia in the pediatric population is unknown, though the prevalence of hyperkalemia in extremely low birth weight premature infants can exceed 50%.[44] Hyperkalemia in pediatric patients is most commonly associated with renal insufficiency, acidosis, and diseases that involve defects in mineralocorticoid, aldosterone, and insulin function.[22]
Military recruits, individuals with sickle cell traits, and people who abuse drugs are at risk for hyperkalemia because of acute rhabdomyolysis. These cases disproportionately occur in males, probably reflecting the higher muscle mass of males, though an underlying hormonal predisposition cannot be absolutely excluded.
Patients with diabetes mellitus are at increased risk for hyperkalemia. In one review of an unselected group of diabetes clinic patients, 15% (270 of 1764) had a serum potassium level higher than 5 mEq/L; however, fewer than 4% had levels higher than 5.4 mEq/L.[45] Clinical risk factors significant in predicting the occurrence of hyperkalemia included renal insufficiency, duration of diabetes mellitus, age, glycosylated hemoglobin levels, and retinopathy—but not the serum glucose level or the drugs used for diabetes treatment.
Use of ACE inhibitors as a risk factor for hyperkalemia is a significant concern, particularly because the indications for these agents in high-risk populations are broad. In a 1998 study, 11% of patients at a Veterans Affairs general medicine outpatient clinic had hyperkalemia; risk factors included elevated blood urea nitrogen (BUN) and serum creatinine, severe diabetes mellitus, heart failure, peripheral vascular disease, and the use of a long-acting drug. Hyperkalemia occurred in less than 6% of patients with normal renal function.[46]
As cardiovascular therapy has evolved, the growing population of patients with chronic heart failure also has come to constitute a high-risk group. The factors promoting the development of hyperkalemia in these patients include underlying renal insufficiency due to poor cardiac output and reduced renal blood flow, as well as the high prevalence of diabetes mellitus in patients with heart failure and the growing use of ACE inhibitors, ARBs, aldosterone inhibitors (eg, spironolactone), and direct renin inhibitors (eg, aliskiren), alone and in combination.[20, 21, 47, 48, 49]
Initial studies examining the risk of hyperkalemia in patients with heart failure who were treated with aldosterone inhibitors revealed only a minor increase in hyperkalemia. However, later studies showed that as the treatment became more widespread, morbidity and mortality from hyperkalemia increased.[50]
International statistics
Hyperkalemia has been reported in less than 5% of the general population worldwide. Hospitalized patients in countries as diverse as England, Australia, and Israel experience hyperkalemia approximately 10% of the time. No racial differences in the incidence of hyperkalemia appear to exist.
As in the United States, risk factors include advanced age, significant prematurity, and the presence of renal failure, diabetes mellitus, and heart failure. Additionally, one series documented an increased incidence of hyperkalemia with cancer and GI disease.[51] Polypharmacy, particularly the use of potassium supplements and potassium-sparing diuretics, in patients with underlying renal insufficiency contributed to hyperkalemia in almost 50% of the cases.
Age-related demographics
Several series document the increasing tendency for hyperkalemia in patients at the extremes of life—that is, small premature infants and elderly people. Renal insufficiency plays a significant role in both groups.
Studies in small premature infants indicate that the incidence of hyperkalemia is increased in infants with a lower GFR, as estimated on the basis of endogenous creatinine clearance. In these cases, hyperkalemia often occurs within the first 48 hours of life. Even full-term infants may have transient hyperkalemia and hyponatremia due to decreased responsiveness to aldosterone (PHAI).[22]
Several factors contribute to the increased propensity for elderly people to become hyperkalemic. Renal function tends to deteriorate with age, even in relatively healthy individuals. The GFR decreases by approximately 1 mL/min each year in people older than 30 years. Renal blood flow also decreases. Oral intake declines, resulting in decreased urine flow rates. Plasma renin activity and aldosterone levels also tend to decrease with age, reducing the ability of the distal nephron to secrete potassium.
Elderly patients are more likely to be taking medications that could interfere with potassium secretion, such as NSAIDs, ACE inhibitors, and potassium-sparing diuretics. Elderly individuals who are bedridden often are placed on subcutaneous heparin, which can decrease aldosterone production.
Sex-related demographics
Men are significantly more prone to hyperkalemia than women are. This difference has been noted in several series and stands in contrast to the increased incidence of hypokalemia in women. The reasons for this discrepancy are unknown. However, neuromuscular disorders, including myotonic and muscular dystrophies and related disorders that can predispose patients to hyperkalemia with succinylcholine administration, are more prevalent in males.[52]
For patients with a defined and transient cause of hyperkalemia, the prognosis is excellent. With correction of the underlying causative condition, full resolution can be expected. However, patients who have ongoing risk factors for hyperkalemia are likely to experience recurrent episodes.
Sudden and rapid onset of hyperkalemia can be fatal. With slow or chronic increase in potassium levels, adaptation occurs via renal excretion, with fractional potassium excretion increasing by as much as 5-10 times the reference range.
Complications of hyperkalemia range from mild ECG changes to cardiac arrest. Weakness is common as well. The primary cause of morbidity and mortality is potassium’s effect on cardiac function.[53] The mortality can be as high as 67% if severe hyperkalemia is not treated rapidly.[54]
In hospitalized patients, hyperkalemia is an independent risk factor for death. In one series, 406 (1.4%) of 29,063 patients who were hospitalized developed hyperkalemia; 58 (14.3%) of the 406 died, with the risk increasing as the potassium level increased.[51]
Whereas 28% of patients with a serum potassium level above 7 mEq/L died, only 9% of those with a potassium level below 6.5 mEq/L died.[51] In 7 of the 58 deaths, the cause of death was directly attributable to hyperkalemia. Most cases resulting in death were complicated by renal failure. It is noteworthy that all of the patients who died of hyperkalemia had normal potassium levels within the 36 hours preceding death.
Interestingly, in a large study of individuals living in the community, serum potassium leveles greater than 5.0 mEq/L correlated with increased mortality, although the mechanisms were not clear.[55]
Many individuals with hyperkalemia are asymptomatic. When present, the symptoms of hyperkalemia are nonspecific and predominantly related to muscular or cardiac function. The most common complaints are weakness and fatigue. Occasionally, a patient may complain of frank muscle paralysis or shortness of breath. Patients also may complain of palpitations or chest pain. Patients may report nausea, vomiting, and paresthesias. The history is most valuable in identifying conditions that may predispose to hyperkalemia.
When hyperkalemia is discovered, investigate potential pathophysiologic mechanisms. For excessive potassium intake, query patients about the following:
Eating disorders - Very unusual diets consisting almost exclusively of high-potassium foods, such as fruits (eg, bananas, oranges, or melons), dried fruits, raisins, fruit juices, nuts, and vegetables with little to no sodium
Heart-healthy diets - Very low–sodium and high-potassium diets recommended for patients with cardiac disease, hypertension, and diabetes mellitus
Use of potassium supplements in over-the-counter herbal supplements, sports drinks, dietary supplements such as noni (Morinda citrifolia) juice, salt substitutes, or prescribed pharmacologic agents
Many patients with hypertension have heard the advice to eat a banana a day because the potassium in it reduces blood pressure. They may not realize that in the case of renal insufficiency and hypertension, this is potentially a life-threatening practice.
With hospitalized patients, review the medication list for potassium supplements or high-dose penicillin G potassium, and review the chart to determine whether the patient has received transfusions. With patients who have undergone cardiac surgery, consider the possibility of residual effects of cardioplegic solutions.
For decreased potassium excretion, query patients regarding a history of renal insufficiency or renal failure. In addition, elicit any history of diabetes mellitus, sickle cell disease or trait, or symptoms of lower urinary tract obstruction. These conditions predispose people to type IV renal tubular acidosis, also called hyperkalemic renal tubular acidosis. Type IV renal tubular acidosis also may accompany other tubulointerstitial disorders, such as polycystic kidney disease or amyloidosis.
Often, patients with type IV renal tubular acidosis have hyporeninemic hypoaldosteronism.[20, 21] One example is diabetes mellitus, where the relative volume overload leads to low renin.
Patients with ureteral diversion into the ileum can develop hyperkalemia due to reabsorption of secreted potassium.
Ask about the use of medications that impair renal potassium excretion, as follows:
Potassium-sparing diuretics, which are especially popular in the treatment of cirrhosis and chronic heart failure
Nonsteroidal anti-inflammatory drugs (NSAIDs)[56]
Angiotensin-converting enzyme (ACE) inhibitors
The combination of spironolactone and ACE inhibitors[57]
Angiotensin-receptor blockers (ARBs)
Direct renin inhibitors (eg, aliskiren)
Cyclosporine or tacrolimus
Antibiotics (eg, pentamidine and trimethoprim-sulfamethoxazole)[58]
Epsilon-aminocaproic acid (EACA)[27]
Oral contraceptive agents, such as drosperinone
For a shift of potassium into the extracellular space, query patients about the following:
Recurrent episodes of flaccid paralysis
Presence of diabetes mellitus
Use of beta-blocker therapy (eg, for hypertension or angina)
Risk factors for rhabdomyolysis, such as heat stroke, chronic alcoholism, seizures, sudden excessive exertion (as in military recruits undergoing basic training), or use of medications that interfere with heat dissipation (eg, tricyclic antidepressants or anesthesia)
Risk factors for tumor lysis syndrome, such as ongoing treatment for widespread lymphoma, leukemia, or other large tumors
Risk factors for hemolysis, such as blood transfusion and sickle cell disease
Redistribution - Metabolic acidosis (diabetic ketoacidosis [DKA]) and catabolic states
Pediatric patients
In a previously well child with acute hyperkalemia, the history should focus on the following:
How the blood sample was obtained
Potassium intake or recent blood product transfusion
Risk factors for transcellular shift of potassium (acidosis) or tissue death or necrosis
Use of medication associated with hyperkalemia (by the child, other family members, pets, or household visitors)
Presence or signs of renal insufficiency
Specific questions may be focused on the following:
Urine output (last void or number of wet diapers) and fluid intake
Cola-colored urine (which may indicate acute glomerulonephritis)
Bloody stool (which may indicate hemolytic-uremic syndrome [HUS])
Drugs present in the household (or used by recent visitors), such as potassium preparations, digoxin, and diuretics
Any history of trauma (crush injuries) or thermal injury (burns)
Medical history, family history, and review of systems should be explored for any of the following:
Acute kidney injury or chronic kidney disease
Hypertension
Diabetes mellitus
Adrenogenital syndromes
Malignancy (tumor lysis syndrome)
The family history should include questions about the following:
In patients with hyperkalemia, vital signs generally are normal. Nonspecific findings can include muscle weakness, fatigue, and depression. Occasionally, cardiac examination may reveal extrasystoles, pauses, or bradycardia resulting from heart block or tachypnea resulting from respiratory muscle weakness. Skeletal muscle weakness and flaccid paralysis may be present, along with depressed or absent deep tendon reflexes. Patients with ileus may have hypoactive or absent bowel sounds.
In general, the results of the physical examination alone do not alert the physician to the diagnosis, except when severe bradycardia is present or muscle tenderness accompanies muscle weakness, suggesting rhabdomyolysis. However, when hyperkalemia has been recognized, evaluation of vital signs is essential for determining hemodynamic stability and identifying the presence of cardiac arrhythmias related to the hyperkalemia.[6]
Ascertain whether the elevated potassium level is real or factitious (see DDx). In a patient who does not have a predisposition to hyperkalemia, repeat the blood test before taking any actions to bring down the potassium level, unless changes are present on electrocardiography (ECG).
Renal function testing is important. If the patient has renal failure, the serum calcium level should be checked because hypocalcemia can exacerbate cardiac rhythm disturbances. Other tests include the following:
Electrocardiogram (ECG)
Urine potassium, sodium, and osmolality
Complete blood count (CBC)
Metabolic profile
Measurement of the trans-tubular potassium gradient (TTKG) remains widely used as a means of assessing whether decreased renal excretion of potassium is contributing to hyperkalemia. Despite its initial promise, however, recent research has called its accuracy into question,[59] and some experts now recommend that TTKG measurement be abandoned.
Depending on the clinical findings and the results of the above laboratory work, the following may be indicated:
Glucose level - In patients with known or suspected diabetes mellitus
Digoxin level - If the patient is on a digitalis medication
Arterial or venous blood gas - If acidosis is suspected
Urinalysis - If signs of renal insufficiency without an already known cause are present (to look for evidence of glomerulonephritis)
Serum cortisol and aldosterone levels - To check for mineralocorticoid deficiency when other causes are eliminated
Serum uric acid and phosphorus assays - For tumor lysis syndrome
Serum creatinine phosphokinase (CPK) and calcium measurements - For rhabdomyolysis
Urine myoglobin test - For crush injury or rhabdomyolysis; suspect if urinalysis reveals blood in the urine but no red blood cells are seen on urine microscopy
The relationship between the serum potassium level and symptoms of hyperkalemia is not consistent. For example, patients with a chronically elevated potassium level may be asymptomatic at much higher levels than other patients are. The rapidity of change in the potassium level influences the symptoms observed at various potassium levels.
In pediatric patients, capillary blood gas sampling should not routinely be used to evaluate for hyperkalemia, because of the significant risks of factitious hyperkalemia.
ECG is vital for assessing the physiologic significance of hyperkalemia. ECG findings generally correlate with the potassium level, but potentially life-threatening arrhythmias can occur without warning at almost any level of hyperkalemia. In patients with organic heart disease and an abnormal baseline ECG, bradycardia may be the only new ECG abnormality.
ECG changes have a sequential progression, which roughly correlate with the potassium level.[2] Early changes of hyperkalemia include tall, peaked T waves with a narrow base, best seen in precordial leads[3] ; shortened QT interval; and ST-segment depression. These changes are typically seen at a serum potassium level of 5.5-6.5 mEq/L.
At a serum potassium level of 6.5-8.0 mEq/L, in addition to peaked T waves, the ECG shows the following:
Prolonged PR interval
Decreased or disappearing P wave
Widening of the QRS (see the images below)
Amplified R wave
View Image
Widened QRS complexes in hyperkalemia.
View Image
Widened QRS complexes in patient whose serum potassium level was 7.8 mEq/L.
At a serum potassium level higher than 8.0 mEq/L, the ECG shows absence of P wave, progressive QRS widening, and intraventricular/fascicular/bundle-branch blocks. The progressively widened QRS eventually merges with the T wave, forming a sine wave pattern. Ventricular fibrillation or asystole follows.
The ECG changes of hyperkalemia reverse with appropriate treatment (see the image below).
View Image
ECG of patient with pretreatment potassium level of 7.8 mEq/L and widened QRS complexes after receiving 1 ampule of calcium chloride. Note narrowing o....
Check serum levels of blood urea nitrogen (BUN) and creatinine to determine whether renal insufficiency is present. If such insufficiency is confirmed, check 24-hour urine for creatinine clearance or estimate the creatinine clearance using the Cockroft-Gault equation to assess whether the degree of renal insufficiency alone explains the hyperkalemia. The Cockroft-Gault equation is as follows:
It must be kept in mind that because the serum creatinine level is dependent on muscle mass, a seemingly normal creatinine level in a geriatric or cirrhotic patient will actually indicate impaired renal function. Tools such as the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas are recommended for estimating glomerular filtration rate (GFR) in these patients.[1] The MDRD formula for estimating the GFR is as follows[60] :
186 ´ serum creatinine (mg/dL)−1.154 ´ age (y)−0.203 (´ 0.742 if female) (´ 1.210 if black)
Measurement of urine potassium and sodium concentrations and urine osmolality is essential to determine whether impairment of renal excretion is contributing to the hyperkalemia. A urine potassium level below 20 mEq/L suggests impaired renal excretion. A urine potassium level above 40 mEq/L suggests intact renal excretory mechanisms, implying that high intake or failure of cell uptake is the major mechanism for hyperkalemia.
A spot urine potassium measurement is the easiest and most commonly obtained test; a 24-hour urine potassium measurement is rarely needed. However, an isolated urine potassium level often is misleading, because the urine potassium concentration is influenced not only by secretion by the cortical collecting tubule but also by the degree of urinary concentration. If urine osmolality is high (>700 mOsm/kg), the absolute value for urine potassium concentration can be misleading and suggest that the kidneys are disposing of potassium appropriately.
For example, if serum potassium is 6 mEq/L and urine potassium 60 mEq/L, the high urine potassium level may be taken as suggesting appropriate renal potassium excretion. However, the final concentration of potassium in the urine depends not only on how much potassium is secreted in response to sodium reabsorption but also on how concentrated the urine is.
In this example, if urine osmolality is 300 mOsm/kg—that is, not concentrated in relation to serum—then a measured urine potassium level of 60 mEq/L indeed suggests renal potassium loss. However, if urine osmolality is 1200 mOsm/kg—that is, concentrated 4-fold in relation to serum—then the urine potassium concentration, in the absence of urinary concentration due to water reabsorption, is 15 mEq/L, which is very low. In the latter case, the conclusion would be that the kidneys are not appropriately excreting potassium.
The trans-tubular potassium gradient (TTKG) was developed to account for the potentially confounding effect of urine concentration on the interpretation of the urine potassium concentration. In effect, the TTKG back-calculates what the serum-to–tubular fluid ratio of potassium would be at the level of the cortical collecting tubule, where potassium is secreted before urine concentration has occurred.
The TTKG is determined by the following equation:
TTKG = (urine K x serum osmolarity)
(serum K x urine osmolarity)
A TTKG of less than 3 suggests a lack of aldosterone effect on the collecting tubules (that is, the kidneys are not excreting potassium appropriately). A TTKG greater than 7 suggests an aldosterone effect, which would be appropriate in the setting of hyperkalemia. In pediatric patients with hyperkalemia, a TTKG greater than 10 is consistent with normal renal excretion of potassium; a TTKG of less than 8 implies inadequate potassium excretion, which is usually secondary to aldosterone deficiency or unresponsiveness. Checking a serum aldosterone level may be helpful.
Measurement of the TTKG was initially considered superior to measurement of urine potassium alone for assessing the contribution of decreased renal excretion to hyperkalemia. However, it is important to recognize that the TTKG is valid for this purpose only if (1) the urine osmolality is greater than the serum osmolality—that is, the urine is concentrated relative to the serum—and (2) the urine sodium is greater than 20 mEq/L—that is, distal delivery of sodium is adequate for potassium excretion.
Furthermore, recent evidence suggesting that urea recycling may influence potassium secretion has cast some doubt on the utility of the TTKG.[59] One assumption inherent in the calculation of the TTKG is that the absorption of osmoles distal to the cortical collecting duct is negligible. If further studies suggest that urea transport can influence potassium handling, this test may have to be abandoned.
The aggressiveness of therapy for hyperkalemia is directly related to the rapidity with which the condition has developed, the absolute level of serum potassium, and the evidence of toxicity. The faster the rise in the potassium level, the higher it has reached, and the greater the evidence of cardiotoxicity, the more aggressive therapy should be.
If the patient has only a moderate elevation in potassium level and no electrocardiographic (ECG) abnormalities, excretion can be increased by using a cation exchange resin or diuretics, and the source of excess potassium (eg, increased intake or inhibited excretion) can be corrected.[61]
In patients with severe hyperkalemia, treatment focuses on immediate stabilization of the myocardial cell membrane, rapid shifting of potassium to the intracellular space, and total body potassium elimination. In addition, all sources of exogenous potassium should be immediately discontinued; including intravenous (IV) and oral potassium supplementation, total parenteral nutrition, and any blood product transfusion. Drugs associated with hyperkalemia should also be discontinued (see Etiology).[62]
Definitive therapy is hemodialysis in patients with renal failure or when pharmacologic therapy is not sufficient. Any patient with significantly elevated potassium levels should undergo dialysis; pharmacologic therapy alone is not likely to bring about adequate reduction of potassium levels in a timely fashion.
After emergency management and stabilization of hyperkalemia, the patient should be hospitalized. Once the potassium level is restored to normal, the potassium-lowering therapies can be discontinued, and the serum potassium level can be monitored. Continuous cardiac monitoring should be maintained.
Further workup should be initiated to determine the inciting cause and to prevent future episodes. Such a workup should include evaluation of sources of potassium intake, causes for decreased renal excretion, and causes for decreased cell uptake of potassium. In most cases, all 3 of those etiologic factors contribute to hyperkalemia. It is particularly important to reevaluate the use of potassium supplements (including salt substitutes) in patients with renal insufficiency or in patients taking medications that impair renal excretion of potassium.
In the prehospital setting, a patient with known hyperkalemia or a patient with renal failure with suspected hyperkalemia should have IV access established and should be placed on a cardiac monitor.[21] In patients with hypotension or marked QRS widening, IV bicarbonate, calcium, and insulin given together with 50% dextrose may be appropriate (see Medication). If digoxin toxicity is suspected, avoid calcium; instead, give magnesium sulfate (2 g over 5 minutes) for patients with cardiac arrhythmias from digitalis toxicity.
In the emergency department (ED), perform continuous ECG monitoring with frequent vital sign checks when hyperkalemia is suspected or when laboratory values indicative of hyperkalemia are received. Measurement of potassium levels at least 1, 2, 4, 6, and 24 hours after identification and treatment of hyperkalemia is recommended.[62]
Discontinue any potassium-sparing drugs or dietary potassium. If the patient is taking digoxin, look for evidence of digitalis toxicity.
If the hyperkalemia is severe (potassium >7.0 mEq/L) or if the patient is symptomatic, begin treatment before diagnostic investigation of the underlying cause. Individualize treatment in accordance with the patient’s presentation, potassium level, and electrocardiographic findings. For example, patients with mild hyperkalemia may not need anything more than enhancement of potassium excretion.
Medications such as calcium, insulin, glucose, and sodium bicarbonate are temporizing measures. Definitive loss of excess potassium can be achieved only with cation exchange resins, dialysis, or increased renal excretion. Begin administration of a cation exchange resin soon after the other drugs have been administered.
Watch for overcorrection of potassium level. For example, in diabetic ketoacidosis (DKA) and many other types of metabolic acidosis, the extracellular potassium level is elevated, yet the patient may have a total body deficit of potassium. Once the clinician initiates therapy for DKA, the extracellular potassium level decreases spontaneously.
Medical treatment of hyperkalemia may be conveniently divided into discrete components. Although these different aspects of hyperkalemia treatment are listed sequentially below, in a step-by-step format, they generally are addressed simultaneously.
Step 1
Administer intravenous (IV) calcium to ameliorate cardiac toxicity, if present. Infuse calcium chloride or calcium gluconate (10 mL of a 10% solution over 2-3 minutes). Onset of action occurs within minutes; duration of action is 30 minutes to an hour.[63]
Step 2
Identify and remove sources of potassium intake. Discontinue oral and parenteral potassium supplements. Remove potassium-containing salt substitutes. Examine the patient’s diet. Change the diet to a low-potassium tube feed or a 2-g potassium ad-lib diet.
Step 3
Enhance potassium uptake by cells to decrease the serum concentration. IV glucose and insulin infusions are very effective in enhancing potassium uptake. A typical regimen is 10 U of regular insulin and 50 mL of dextrose 50% in water (D50W).The onset of action is within 20-30 minutes, and the duration is variable, ranging from 2 to 6 hours. Continuous infusions of insulin and glucose-containing IV fluids can be used for prolonged effect.
IV insulin (even when administered with dextrose) can cause hypoglycemia. Patients with acute kidney injury and chronic kidney disease are especially susceptible. Measure glucose and potassium levels every 2 hours. Continue monitoring glucose levels for at least 6 hours after administering insulin-glucose.[64]
A retrospective study by Pierce et al of 149 patients with low estimated glomerular filtration rate (eGFR) who received IV insulin for hyperkalemia found no significant difference in the rate of hypoglycemia (blood glucose ≤70 mg/dL) or severe hypoglycemia (< 50 mg/dL) with 10 U versus 5 U of insulin. Rates of hypoglycemia in the 10-U and 5-U groups were 16.7% and 19.7%, respectively (P = 0.79). Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). [65]
Correct metabolic acidosis with sodium bicarbonate. Because of the variable effect of different forms of metabolic acidosis on the serum potassium level, this therapeutic modality is less effective and less predictable in producing a hypokalemic response, especially in patients with chronic renal failure. Nonetheless, if the acidosis is severe, then a trial of parenteral sodium bicarbonate therapy is warranted.
Beta-adrenergic agonists also are quite effective but are perhaps somewhat more controversial and more likely to produce side effects. In the United States, the most commonly used preparation is nebulized albuterol. The dose for treating hyperkalemia, 10 mg, is substantially higher than the usual dose for the treatment of bronchospasm and requires the assistance of a respiratory therapist. The peak hypokalemic effect occurs at 90 minutes. This therapy is highly effective and is preferred to alkali therapy in patients with renal failure.
Parenteral isoproterenol and albuterol also decrease potassium. However, isoproterenol is not commonly used, and parenteral albuterol is not available in the United States. Some investigators have reported tachycardia and chest discomfort with the use of beta-agonist therapy for hyperkalemia. Discontinue beta-adrenergic antagonists.
Step 4
Increase potassium excretion from the body. Renal excretion is enhanced easily in patients with normal kidney function by administering IV saline accompanied by a loop diuretic (eg, furosemide). Discontinue potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and other drugs that inhibit renal potassium excretion. Monitor volume status and aim to maintain euvolemia.
Renal excretion can be enhanced by administration of an aldosterone analogue, such as 9-alpha fluorohydrocortisone acetate. Fluorohydrocortisone is especially helpful in patients with hyporeninemia or hypoaldosteronism. It has been increasingly used in solid-organ transplant recipients who have chronic hyperkalemia from calcineurin inhibitor use. Usually, serum potassium returns to normal after about 48 hours.[66]
Sodium polystyrene sulfonate
Gastrointestinal (GI) excretion can be increased through the use of cation exchange resins such as sodium polystyrene sulfonate (SPS). SPS can be administered orally or rectally (as a retention enema). Because the major site of action for this drug is the colon, rectal administration is preferred for hyperkalemic emergencies. The effectiveness of SPS is enhanced if the enema can be retained for 1 hour.
SPS is not useful for acute control of hyperkalemia, because its effect on potassium is delayed for at least 2 hours, peaking at 4-6 hours. SPS can decrease serum potassium by 2 mEq/L.
Oral SPS is useful in patients with advanced renal failure who are not yet on dialysis or transplant candidates. One or more daily doses of 15 g can control mild to moderate hyperkalemia effectively, with little inconvenience to patients.
Although SPS has a long history of use for hyperkalemia, its safety and efficacy have been questioned.[64, 67, 68, 61] The US Food and Drug Administration (FDA) advises against its use in patients who do not have normal bowel function (eg, postoperative patients who have not had a bowel movement since their procedure) or those who are at risk for constipation or impaction.[69] SPS should be discontinued in patients who become constipated, and repeat doses should not be given to patients who have not passed a bowel movement.
In addition, the FDA cautions that giving SPS with sorbitol, an osmotic cathartic used to prevent fecal impaction from SPS and to speed delivery of resin to the colon, has been associated with cases of intestinal necrosis, some of them fatal.[69] Current evidence indicates that this serious side effect can occur with SPS even when preparation does not contain any sorbitol.[70]
Patiromer
Patiromer sorbitex calcium (Veltassa) is a nonabsorbed, cation exchange polymer that contains a calcium-sorbitol counterion. It increases fecal potassium excretion by binding potassium in the lumen of the GI tract. It is indicated for hyperkalemia. It should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
FDA approval of patiromer was based on the AMETHYST-DN trial. Results showed that among patients with hyperkalemia and diabetic kidney disease taking RAAS inhibitors, patiromer resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 week.[71]
The OPAL-HK trial showed that patiromer was well tolerated, decreased serum K(+) , and, compared with placebo, reduced recurrent hyperkalemia in patients with chronic kidney disease (CKD) and heart failure who were hyperkalemic while taking renin-angiotensin-aldosterone system inhibitors (RAASi). In the study, patiromer was given to patients with CKD who were taking RAASi and had serum K(+) levels >5.1 mEq/L to < 6.5 mEq/L (n=243) for 4 weeks. Patients whose K(+) levels were ≥3.8 mEq/L to < 5.1 mEq/L at the end of week 4 entered an 8-week randomized withdrawal phase and were randomly assigned to continue patiromer or switch to placebo.[72]
The primary efficacy endpoint was the between-group difference in median change in the serum K(+) over the first 4 weeks of the withdrawal phase. The median increase in serum K(+) from baseline of the withdrawal phase was greater with placebo (n = 22) than patiromer (n = 27) (P < 0.001). Recurrent hyperkalemia (serum K(+) ≥5.5 mEq/L) occurred in 52% of patients on placebo and 8% of those on patiromer (P < 0.001).[72]
Sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate (Lokelma) was approved by the FDA in May 2018 to treat hyperkalemia in adults. It preferentially captures potassium in exchange for hydrogen and sodium, which reduces the free potassium concentration in the lumen of the GI tract, and thereby lowers the serum potassium level. Like patiromer, sodium zirconium cyclosilicate should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Approval was based on the HARMONIZE clinical trial in patients with serum potassium levels of 5.1 mEq/L or higher. In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients achieving normokalemia by 24 hours and 98% by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L, 4.5 mEq/L, and 4.4 mEq/L for 5 g, 10 g, and 15 g, respectively; 5.1 mEq/L for placebo; P < 0.001 for all comparisons).[73]
The HARMONIZE trial also included patients with heart failure who were maintained on renin-angiotensin-aldosterone system inhibitors (RAASi), which are known to cause elevated serum potassium levels. Compared with placebo, all 3 zirconium cyclosilicate doses lowered potassium and effectively maintained normokalemia for 28 days in patients with heart failure without the need to adjust RAASi regimens.[74]
Step 5
Emergency dialysis is a final recourse for patients who are experiencing potentially lethal hyperkalemia that has not responded to more conservative measures or for patients who have complete renal failure. Initiation of dialysis can often take several hours; therefore, even if dialysis is contemplated, the other therapeutic modalities should be instituted as a bridge to dialysis.
The final step in the medical management of hyperkalemia is to determine the cause of hyperkalemia in order to prevent future episodes. This should include examination of the following:
Surgical intervention generally is not needed for the care of a patient with hyperkalemia. Patients with metabolic acidosis and consequent hyperkalemia due to ischemic gut obviously require exploration. Patients with hyperkalemia due to rhabdomyolysis may need surgical decompression of swollen, ischemic muscle compartments. Patients without end-stage renal disease who require hemodialysis for control of hyperkalemia require placement of a hemodialysis catheter for emergency dialysis.[75]
In patients with solid tumors, tumor debulking may be considered as a means of decreasing the risk of hyperkalemia from tumor lysis syndrome.[76]
Hypercalcemia due to excessive calcium administration
Hypocalcemia from excessive bicarbonate therapy
Chest discomfort or tachycardia due to beta-agonist therapy
Hypoglycemia or hyperglycemia complicating glucose and insulin administration
Metabolic alkalosis and tetany due to excessive sodium bicarbonate administration
Volume depletion, metabolic alkalosis, renal insufficiency, hypocalcemia, hypomagnesemia, and hypophosphatemia due to aggressive loop diuretic use
Colon perforation due to exchange resin administration
Treatment of pseudohyperkalemia may result in hypokalemia; thus, treatment of non–life-threatening hyperkalemia should be deferred pending verification of hyperkalemia.
A low-potassium diet containing 2 g of potassium is recommended so as to minimize potassium intake in patients at risk for hyperkalemia. In particular, potassium intake must be closely monitored (and possibly restricted) in patients with renal failure.
No restrictions on activity are necessary unless continuous monitoring for cardiotoxicity is required.
Inform patients at risk for hyperkalemia about dietary sources of potassium, including salt substitutes. Adjust the diet to decrease potassium dietary load. Adjust medications that predispose to or exacerbate hyperkalemia.
In a retrospective observational study of 27,355 patients with diabetes, Raebel et al concluded that potassium monitoring can reduce the incidence of serious hyperkalemia-associated adverse events in patients with diabetes and chronic kidney disease who are undergoing renin-angiotensin-aldosterone system inhibitor therapy.[16] The investigators found that for monitored patients with diabetes alone, the adjusted relative risk was 0.50, whereas for monitored patients who also had chronic kidney disease, the adjusted relative risk was 0.29.
For patients with severe hyperkalemia or renal failure, early consultation with a nephrologist for aid in implementing efficient therapy and plans for dialysis is highly recommended. In addition, these patients should be admitted to an intensive care unit (ICU).
Consultations with the following specialists may be necessary in cases of hyperkalemia that result from certain conditions or disease states:
Pediatric intensivist or neonatologist – For life-threatening hyperkalemia (hyperkalemia with ECG changes) in infants and children
Social services specialist – For hyperkalemia developing in children after unintentional ingestions or poisonings
Cardiologist - For emergency pacemaker placement in patients with refractory heart block
Hematologist/oncologist – For hyperkalemia resulting from tumor lysis syndrome
Nutritional support specialist - For hyperkalemia caused by renal failure, which requires close regulation of potassium and sodium intake
Endocrinologist – For suspected mineralocorticoid abnormalities (eg, congenital adrenal hyperplasia)
For patients whose hyperkalemia resulted from a single, clearly defined episode (eg, acute exertional rhabdomyolysis or drug-induced hemolysis), infrequent monitoring of serum potassium generally suffices. However, for patients who have conditions or medications that will continue to predispose to hyperkalemia, more frequent monitoring of serum potassium is required. For patients at high risk, monthly measurements are indicated.
Continuing care relates to the disease process that led to the hyperkalemia. For patients who have recurrent or constant hyperkalemia (eg, those with diabetic nephropathy and type IV renal tubular acidosis), long-term therapy with an oral loop diuretic and SPS may be indicated. For pseudohypoaldosteronism type II, the treatment of choice is a thiazide diuretic.
The risk of severe hypoglycemia for patients with acute kidney injury or end-stage renal disease is heightened in patients with lower body weight and creatinine clearance. Sufficient dextrose in the patient’s treatment regimen can minimize the risk.[77] In patients with salt-wasting congenital adrenal hyperplasia, corticosteroid and mineralocorticoid supplementation are necessary.
The goals of pharmacotherapy are to reduce potassium levels and morbidity and to prevent complications. Calcium protects the myocardium from the deleterious effects of hyperkalemia. Beta-adrenergic agents, insulin, and loop diuretics stimulate cellular uptake of potassium, lowering the serum potassium level.
Clinical Context:
Calcium increases the threshold potential, thus restoring the normal gradient between threshold potential and resting membrane potential, which is abnormally elevated in hyperkalemia. Onset of action is within 5 minutes, and duration of action is about 30-60 minutes. Doses should be titrated with constant monitoring of ECG changes during administration; repeat the dose if ECG changes do not normalize within 3-5 minutes.
Clinical Context:
Calcium prevents the deleterious cardiac effects of severe hyperkalemia that may occur before the serum potassium level is corrected. Because of its irritating effects when administered parenterally, calcium chloride is generally considered a second choice, after calcium gluconate.
Calcium antagonizes the cardiotoxicity of hyperkalemia by stabilizing the cardiac cell membrane against undesirable depolarization. Onset of effect is rapid (≤ 15 minutes) but relatively short-lived. These agents are the first-line treatment for severe hyperkalemia (ie, >7 mEq/L), when the electrocardiogram (ECG) shows significant abnormalities (eg, widening of QRS interval, loss of P wave, or cardiac arrhythmias). Calcium usually is not indicated when the ECG shows only peaked T waves.
Calcium has no effect on the serum level of potassium. For that reason, administration of calcium should be accompanied by the use of other therapies that actually help lower serum potassium levels.
Calcium chloride contains about 3 times more elemental calcium than an equal volume of calcium gluconate: 1 g of calcium chloride has 270 mg (13.5 mEq) of elemental calcium, whereas 1 g of calcium gluconate has 90 mg (4.5 mEq). Therefore, when hyperkalemia is accompanied by hemodynamic compromise, calcium chloride is preferred to calcium gluconate. Other calcium salts (eg, glubionate and gluceptate) have even less elemental calcium than calcium gluconate and generally are not recommended for therapy of hyperkalemia.
Clinical Context:
Albuterol is an adrenergic agonist that has an additive effect with insulin and glucose, which may in turn help shift potassium into the intracellular space. This agent lowers the serum potassium level by 0.5-1.5 mEq/L. It can be very beneficial in patients with renal failure when fluid overload is concern. Onset of action is 30 minutes; duration of action is 4-6 hours for the immediate-release product.
Through activation of cyclic adenosine monophosphate (cAMP), these agonists stimulate the sodium-potassium–adenosine triphosphatase (Na+ -K+ -ATPase) pump, thereby shifting potassium into the intracellular compartment. However, these shifts in potassium occur primarily during exercise rather than at rest.
Clinical Context:
Regular insulin stimulates cellular uptake of potassium within 20-30 minutes and lasts for 4-6 hours. The serum potassium concentration typically drops by 0.5-1.2 mEq/L. Administer glucose along with insulin to prevent hypoglycemia. Monitor blood sugar levels frequently. Although the effect is rapid, it is temporary; therefore, insulin therapy should be followed by therapy that actually enhances potassium clearance (eg, sodium polystyrene sulfonate [SPS]).
Insulin is administered with glucose to facilitate the uptake of glucose into muscle cells, bringing potassium with it, primarily by enhancing the activity of the Na+ -K+ -ATPase pump and thereby temporarily lowering serum potassium levels.
Clinical Context:
Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Furosemide has a slow onset of action (frequently 1 hour), and its effect on lowering the potassium level is inconsistent. Large doses may be needed in renal failure.
Individualize the dose to the patient. For the treatment of edema, depending on the response, administer in increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants and children, give 1-2 mg/kg every 6-12 hours. If the diuretic response is not satisfactory, furosemide may be titrated in increments of 1 mg/kg (no sooner than 2 hours after the previous dose) until a satisfactory effect is achieved (up to 6 mg/kg).
Oral absorption of furosemide varies from person to person. If the patient requires rapid and effective therapy, the intravenous (IV) route is preferred. Continuous infusion of furosemide (at rates as high as 40 mg/hr) is occasionally used for severe edema but rarely is required for the treatment of hyperkalemia.
Clinical Context:
Bumetanide increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Individualize the dose to the patient.
For treatment of edema in adults, start at 0.5-1 mg IV or intramuscularly (IM); if the desired response is not achieved, administer a second or third dose at 2-3 hour intervals. Titrate to a maximum dosage of 10 mg/day. Rarely, dosages as high as 20 mg/day are used for edema in patients with renal impairment; however, they generally are not required for treatment of hyperkalemia.
Clinical Context:
Ethacrynic acid increases excretion of water by interfering with the chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. For treatment of edema in adults, start at 0.5-1 mg/kg IV. Typically, 1 dose is all that is needed; occasionally, however, a second dose may be given after 2-4 hours. For second doses, a new injection site should be used so as to avoid possible thrombophlebitis. Single IV doses higher than 100 mg are not recommended.
Loop diuretics markedly enhance renal potassium excretion and thus lower serum levels. Parenterally administered drugs have a more rapid onset of action and are preferable in emergency situations. Simultaneous administration of saline can prevent severe volume depletion.
Clinical Context:
SPS exchanges sodium for potassium and binds it in the gut, primarily in the large intestine, decreasing the total body potassium level by approximately 0.5-1 mEq/L. Multiple doses are usually necessary.
Onset of action ranges from 2 to 24 hours after oral administration and is even longer after rectal administration. The duration of action is 4-6 hours. Do not use SPS as a first-line therapy for severe life-threatening hyperkalemia; use it in the second stage of therapy.
The US Food and Drug Administration (FDA) notes that SPS has been associated with intestinal necrosis and other serious gastrointestinal (GI) complications and advises against its use in patients who do not have normal bowel function. Concomitant use of sorbitol with sodium polystyrene sulfonate has been implicated in cases of colonic necrosis.[62]
Clinical Context:
Patiromer sorbitex calcium is a nonabsorbed, cation exchange polymer that contains a calcium-sorbitol counterion. It increases fecal potassium excretion by binding potassium in the lumen of the GI tract. It is indicated for hyperkalemia. It should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Clinical Context:
Potassium binder; nonabsorbed zirconium silicate that preferentially captures potassium in exchange for hydrogen and sodium. It increases fecal potassium excretion through binding of potassium in the lumen of the GI tract; binding of potassium reduces the free potassium concentration in the GI lumen, thereby lowering serum potassium level. It is indicated for treatment of nonemergent hyperkalemia in adults.
Clinical Context:
The bicarbonate ion neutralizes hydrogen ions and raises urinary and blood pH. Onset of action occurs within minutes; duration of action is approximately 15-30 minutes. Monitor blood pH to avoid excess alkalosis. Use the 8.4% solution in adults and children and the 4.2% solution in children younger than 2 years. The adult dose for hyperkalemia is 50 mEq IV over 5 minutes. Consider methods of enhancing potassium removal or excretion, as appropriate.
The following formula may be used to estimate the dose that should be administered for metabolic acidosis:
This formula has many limitations; however, it allows the practitioner to make a rough determination of the amount of bicarbonate required and subsequently to titrate against the pH and anion gap.
In patients with severe metabolic acidosis, sodium bicarbonate IV is used as a buffer that breaks down to water and carbon dioxide after binding free hydrogen ions. By increasing the pH, sodium bicarbonate promotes a temporary potassium shift from the extracellular to the intracellular environment. It also enhances the effectiveness of insulin in patients with acidemia. These agents have been successfully used in the treatment of acute overdose of slow-release oral potassium preparations.
The use of sodium bicarbonate can be considered in treatment of hyperkalemia even in the absence of metabolic acidosis, though it is less likely to be effective in this context. This agent also increases sodium delivery to the kidney, which assists in potassium excretion.
Clinical Context:
Magnesium is a cofactor in enzyme systems involved in neurochemical transmission and muscular excitability. In adults, potassium 60-180 mEq/day, magnesium 10-30 mEq/day, and phosphate 10-40 mmol/day may be necessary for optimum metabolic response. Give IV for acute suppression of torsades de pointes. Repeat doses are dependent on the continuing presence of patellar reflex and adequate respiratory function.
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causes hyperkalemia (high serum potassium levels)?What are the risk factors for development of hyperkalemia (high serum potassium level)?When can excessive potassium intake alone cause hyperkalemia (high serum potassium level)?What are the most common causes of decreased excretion of potassium in hyperkalemia (high serum potassium level)?What causes potassium to shift from the intracellular to the extracellular space?Which clinical situations suggest a shift of potassium from the intracellular to the extracellular space?Can epsilon aminocaproic acid (EACA) cause hyperkalemia (high serum potassium levels)?What are cardiac and skeletal muscle effects of hyperkalemia (high serum potassium levels)?What is the etiology of hyperkalemia (high serum potassium levels)?What causes increased potassium intake in patients with hyperkalemia (high serum potassium level)?What causes decreased potassium excretion in patients with hyperkalemia (high serum potassium level)?Which disorders cause type IV 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the role of type II pseudohypoaldosteronism (PHAII) (Gordon syndrome) in the development of hyperkalemia (high serum potassium level)?How does type II pseudohypoaldosteronism (PHAII) (Gordon syndrome) affect hyperkalemia (high serum potassium level)?How do chloride homeostasis disorders cause hyperkalemia (high serum potassium levels)?How does nephronophthisis cause hyperkalemia (high serum potassium levels)?What causes hyperkalemic period paralysis (HYPP)?Why are people with diabetes mellitus at higher risk for developing hyperkalemia (high serum potassium level)?In what populations is hyperkalemia (high serum potassium level) most common?What is the prevalence of hyperkalemia (high serum potassium level) among children?Why are military recruits, individuals with sickle cell traits, and people who abuse drugs at risk for hyperkalemia (high serum potassium level)?What clinical factors increase the risk of hyperkalemia (high serum potassium level) in patients with diabetes mellitus?Are 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levels)?How is metabolic acidosis corrected in patients with hyperkalemia (high serum potassium level)?Are parenteral isoproterenol and albuterol used in the treatment of hyperkalemia (high serum potassium level)?How is potassium excretion increased in the treatment of hyperkalemia (high serum potassium level)?How is sodium polystyrene sulfonate (SPS) used in the treatment of hyperkalemia (high serum potassium level)?Is sodium polystyrene sulfonate (SPS) a safe and effective treatment in patients with hyperkalemia (high serum potassium level)?How is patiromer sorbitex calcium (Veltassa) used in the treatment of hyperkalemia (high serum potassium level)?Is patiromer sorbitex calcium (Veltassa) safe and effective in the treatment of hyperkalemia (high serum potassium level)?When is emergency dialysis indicated in the treatment of hyperkalemia (high serum potassium level)?What is the final step in the medical treatment of hyperkalemia (high serum potassium level)?When is surgery indicated for hyperkalemia (high serum potassium level)?What are possible complications of hyperkalemia (high serum potassium level) treatment?What are the diet and activity recommendations for patients with hyperkalemia (high serum potassium level)?How can hyperkalemia (high serum potassium level) be prevented?Which specialists should be consulted in the management of hyperkalemia (high serum potassium level)?How and when should patients with hyperkalemia (high serum potassium level) be monitored?Which medications in the drug class Calcium salts are used in the treatment of Hyperkalemia?Which medications in the drug class Beta-adrenergic agonists are used in the treatment of Hyperkalemia?Which medications in the drug class Antidiabetics, Insulins are used in the treatment of Hyperkalemia?Which medications in the drug class Diuretics, Loop are used in the treatment of Hyperkalemia?Which medications in the drug class Potassium Binders are used in the treatment of Hyperkalemia?Which medications in the drug class Alkalinizing Agents are used in the treatment of Hyperkalemia?Which medications in the drug class Electrolytes are used in the treatment of Hyperkalemia?
Eleanor Lederer, MD, FASN, Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc<br/>Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.
Coauthor(s)
Lina Mackelaite, MD, Assistant Professor of Medicine, University of Louisville School of Medicine
Disclosure: Nothing to disclose.
Vibha Nayak, MD, Assistant Professor of Nephrology, Director of Home Dialysis, Kidney Disease Program, University of Louisville School of Medicine
Disclosure: Nothing to disclose.
Zygimantas C Alsauskas, MD, Assistant Professor of Medicine, Division of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Chief Editor
Vecihi Batuman, MD, FASN, Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System
Disclosure: Nothing to disclose.
Acknowledgements
Son Dinh, MD Nephrologist, Southland Renal Medical Group, Inc
Son Dinh, MD is a member of the following medical societies: American Society of Nephrology and National Kidney Foundation
Disclosure: Nothing to disclose.
Anil Kumar Mandal, MD Clinical Professor, Department of Internal Medicine, Division of Nephrology, University of Florida School of Medicine
Anil Kumar Mandal, MD is a member of the following medical societies: American College of Clinical Pharmacology, American College of Physicians, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.
Rosemary Ouseph, MD Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine
Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Royal College of Physicians
[Guideline] Alfonzo A, Soar J, MacTier R, et al. Treatment of Acute Hyperkalaemia in Adults. The Renal Association. Available at http://www.renal.org/guidelines/joint-guidelines/treatment-of-acute-hyperkalaemia-in-adults#sthash.vXcD0IG3.QqdB4c5G.dpbs. March 1, 2014; Accessed: October 6, 2015.
US Food and Drug Administration. Safety: Kayexalate (sodium polystyrene sulfonate) powder. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm186845.htm. Accessed: October 5, 2015.
Schafers S, Naunheim R, Vijayan R. Incidence of hypoglycemia following insulin-based acute stabilization of hyperkalemia treatment. J Hospit Med. 15 Nov 2011. Early online:
Widened QRS complexes in patient whose serum potassium level was 7.8 mEq/L.
Widened QRS complexes in hyperkalemia.
Widened QRS complexes in patient whose serum potassium level was 7.8 mEq/L.
ECG of patient with pretreatment potassium level of 7.8 mEq/L and widened QRS complexes after receiving 1 ampule of calcium chloride. Note narrowing of QRS complexes and reduction of T waves.
Widened QRS complexes in patient whose serum potassium level was 7.8 mEq/L.
ECG of patient with pretreatment potassium level of 7.8 mEq/L and widened QRS complexes after receiving 1 ampule of calcium chloride. Note narrowing of QRS complexes and reduction of T waves.
Hyperkalemia diagnosis and treatment flow chart.
Widened QRS complexes in hyperkalemia.
Factor
Effect on Plasma K+
Mechanism
Aldosterone
Decrease
Increases sodium resorption, and increases K+ excretion
Insulin
Decrease
Stimulates K+ entry into cells by increasing sodium efflux (energy-dependent process)
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