Hyperkalemia is defined as a serum or plasma potassium level above the upper limits of normal, usually greater than 5.0 mEq/L to 5.5 mEq/L. While mild hyperkalemia is usually asymptomatic, high levels of potassium may cause life-threatening cardiac arrhythmias, muscle weakness or paralysis. Symptoms usually develop at levels higher levels, 6.5 mEq/L to 7 mEq/L, but the rate of change is more important than the numerical value. Patients with chronic hyperkalemia may be asymptomatic at increased levels, while patients with dramatic, acute potassium shifts may develop severe symptoms at lower ones. Infants have higher baseline levels than children and adults.
Pseudohyperkalemia is quite common and represents a false elevation in measured potassium due to specimen collection, handling, or other causes. Hyperkalemia should always be confirmed before aggressive treatment in cases where the serum potassium is elevated without explanation. True hyperkalemia may be caused by increased potassium intake, transcellular movement of intracellular potassium into the extracellular space, and decreased renal excretion. The urgency of therapy depends on symptoms, serum levels and explanation for hyperkalemia.
The most common cause of hyperkalemia is pseudohyperkalemia, which is not reflective of the true serum potassium levels. Pseudohyperkalemia is most commonly due to hemolysis of the sample causing intracellular potassium to be measured in the serum. Hemolysis is more common when a syringe is used as compared to a vacuum device. The use of tourniquets and excessive fist pumping during blood draw also increases the risk. Specimens drawn from patients with leukocytosis or thrombocytosis are also frequently associated with falsely elevated potassium concentrations.
Increased Potassium Intake
Increased potassium intake from food is a very uncommon cause of hyperkalemia in adult patients with normal renal function but can be an important cause in those with kidney disease. Foods with very high potassium content include dried fruits, seaweed, nuts, molasses, avocados, and Lima beans. Many vegetables that are also high in potassium include spinach, potatoes, tomatoes, broccoli, beets, carrots, and squash. High-potassium-containing fruits include kiwis, mangoes, oranges, bananas, and cantaloupe. Red meats are also rich in potassium. While generally safe to consume even in large quantities by patients with normal potassium homeostasis, these foods should be avoided in patients with the severe renal disease or other underlying conditions or medications that predispose them to hyperkalemia. Intravenous intake through high potassium containing fluids, particularly total parenteral nutrition, medications with high potassium content and massive blood transfusions can significantly elevate serum potassium levels.
Intracellular Potassium Shifts
Cellular injury can release large quantities of intracellular potassium into the extracellular space. This can be due to rhabdomyolysis from a crush injury, excessive exercise, or other hemolytic processes. Metabolic acidosis may cause intracellular potassium to shift into the extracellular space without red cell injury. Metabolic acidosis is most frequently caused by decreased, effective, circulating, arterial blood volume. Sepsis or dehydration may lead to hypotension and decreased tissue perfusion leading to metabolic acidosis with subsequent potassium elevation. Insulin deficiency and diabetic ketoacidosis may cause dramatic extracellular shifts causing measured serum potassium to be elevated in the setting of whole body potassium depletion. Certain medications, such as succinylcholine may cause severe, acute potassium elevations in patients with up-regulation of receptors, particularly in the setting of subacute neuromuscular disease. Tumor lysis syndrome, particularly in patients receiving chemotherapy for hematogenous malignancy, may cause acute hyperkalemia due to massive cancer cell death. Hyperkalemic periodic paralysis is a rare, autosomal dominant condition that causes potassium to shift into the extracellular space due to impaired sodium channel function in skeletal muscle.
Impaired Potassium Excretion
Acute or chronic kidney disease is a common cause of hyperkalemia. Hyperkalemia is usually not seen until the glomerular filtration rate falls below 30 ml/min. This is commonly due to primary renal dysfunction but may be from acute volume depletion from dehydration or bleeding or decreased circulating blood volume due to congestive heart failure or cirrhosis. Tubular dysfunction due to aldosterone deficiency or insensitivity can also cause hyperkalemia.
Hyperkalemia is unusual in the general population, reported in less than 5% of the population, worldwide, but may affect up to 10% of all hospitalized patients. Most cases in hospitalized patients are due to medications and renal insufficiency. Diabetes, malignancy, extremes of age, and acidosis are other important causes in inpatients. Hyperkalemia is rare in children but may occur in up to 50% of premature infants. Hyperkalemia is more commonly reported in men than women perhaps due to increased muscle mass and higher rates of rhabdomyolysis and increased prevalence of neuromuscular disease.
Potassium is usually an intracellular cation. The sodium-potassium pump is responsible for maintaining potassium within the cells. Most potassium is excreted in urine through the kidneys with about 10% in sweat and stool.
Most patients are relatively asymptomatic with mild and even moderate hyperkalemia. Elevated potassium is often discovered on screening labs done in patients with nonspecific complaints or those with suspected electrolyte abnormalities due to infection, dehydration or hypoperfusion. Historical clues include the history of renal disease, diabetes, chemotherapy, major trauma, crush injury, or muscle pain suggestive of rhabdomyolysis. Medications that may predispose to the development of hyperkalemia include digoxin, potassium-sparing diuretics, non-steroidal anti-inflammatory drugs, ace-inhibitors or recent intravenous (IV) potassium, total parenteral nutrition, potassium penicillin or succinylcholine. Patients may complain of weakness, fatigue, palpitations, or syncope.
Physical exam findings may include hypertension and edema in the setting or renal disease. There may also be signs of hypoperfusion. Muscle tenderness may be present in patients with rhabdomyolysis. Jaundice may be seen in patients with hemolytic conditions. Patients may have muscle weakness, flaccid paralysis, or depressed deep tendon reflexes.
The first test that should be ordered in a patient with suspected hyperkalemia is an ECG since the most lethal complication of hyperkalemia is cardiac condition abnormalities which can lead to dysrhythmias and death.
Elevated potassium causes ECG changes in a dose-dependent manner:
It should be noted that the rate of rising in serum potassium is a greater factor than the level. Patients with chronic hyperkalemia may have relatively normal EGCs even at high levels, and significant ECG changes may be present at much lower levels in patients with sudden spikes in serum potassium.
Additional laboratory testing should include serum blood urea nitrogen and creatinine to assess renal function, and urinalysis to screen for the renal disease. Urine potassium, sodium, and osmolality may also be helpful in evaluating the cause. In patients with the renal disease, the serum calcium level should also be checked because hypocalcemia may exacerbate the cardiac effects of hyperkalemia. Complete blood count to screen for leukocytosis or thrombocytosis may also be helpful. Serum glucose and blood gas analysis should be ordered in diabetics and patients with suspected acidosis. Lactate dehydrogenase should be ordered in patients with suspected hemolysis. Creatinine phosphokinases and urine myoglobin should be ordered in patients with suspected rhabdomyolysis. Uric acid and phosphorus should be ordered in patients with suspected tumor lysis syndrome. Digoxin toxicity may cause hyperkalemia so serum levels should be checked in patients on digoxin. If no other cause is found, consider cortisol and aldosterone levels to assess for mineralocorticoid deficiency.
Since pseudohyperkalemia is so common, confirmation should be obtained in asymptomatic patients without typical ECG changes prior to initiating aggressive therapy.
The urgency with which hyperkalemia should be managed depends on how rapidly the condition developed, the absolute serum potassium level, the degree of symptoms, and the cause.
Patients with neuromuscular weakness, paralysis or ECG changes and elevated potassium of more than 5.5 mEq/L in patients at risk for ongoing hyperkalemia, or confirmed hyperkalemia of 6.5 mEq/L should have aggressive treatment. Exogenous sources of potassium should be immediately discontinued. Calcium therapy will stabilize the cardiac response to hyperkalemia and should be initiated first in the setting of cardiac toxicity. Calcium does not alter the serum concentration of potassium but is first-line therapy in hyperkalemia related arrhythmias and ECG changes. Calcium chloride contains three times more elemental calcium than calcium gluconate but is more irritating to peripheral vessels and more likely to cause tissue necrosis with extravasation, so it is usually only given through central venous lines or peripherally in cardiac arrest. Thus, calcium gluconate is the usual initial drug of choice in patients with evidence of cardiac toxicity. Insulin and glucose, or insulin alone in hyperglycemic patients, will drive the potassium back into the cells, effectively lowering serum potassium. A common regimen is ten units of regular insulin given with 50 ml of a 50% dextrose solution (D50). Patients should be monitored closely for development of hypoglycemia. A 10% dextrose infusion at 50-75 ml/hour is associated with less hypoglycemia than bolus dosing with D50. Beta-2 adrenergic agents such as albuterol will also shift potassium intracellularly. To be effective, beta-2 agonists are given in much higher doses than commonly used for bronchodilation. Sodium bicarbonate infusion may be helpful in patients with metabolic acidosis. Bolus dosing of sodium bicarbonate is less effective.
Loop or thiazide diuretics may be helpful in enhancing potassium excretion. They may be used in non-oliguric, volume overloaded patients but should not be used as monotherapy in symptomatic patients. Gastrointestinal cation exchangers such as patiromer may be helpful, particularly in patients with renal insufficiency who cannot receive immediate dialysis. Sodium polystyrene sulfonate, though commonly used, is falling out of favor due to lack of effectiveness and adverse effects, particularly bowel necrosis in elderly patients. If used due to lack of alternatives, it should not be given with sorbitol, which increases toxicity. Hemodialysis should be performed in patients with end-stage renal disease or severe renal impairment.
For patients with mild transient hyperkalemia, the prognosis is excellent if the inciting cause is addressed and treated. Sudden onset, extreme hyperkalemia can cause cardiac arrhythmias that can be lethal in up to two-thirds of cases if not rapidly treated. Hyperkalemia is an independent risk factor for death in hospitalized patients.