- Author: Eleanor Lederer, MD, FASN; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
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.
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.
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.
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.
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.
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.
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.
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]).
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.
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.
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.
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.
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.
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.
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.
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:
HCO3− (mEq) = 0.5 (L/kg) × weight (kg) × (24 − serum HCO3− [mEq/L])
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.
Magnesium sulfate is used for hyperkalemic patients with cardiac arrhythmias from digitalis toxicity.
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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|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)|
|Beta-adrenergic agents||Decrease||Increases skeletal muscle uptake of K+|
|Alpha-adrenergic agents||Increase||Impairs cellular K+ uptake|
|Acidosis (decreased pH)||Increase||Impairs cellular K+ uptake|
|Alkalosis (increased pH)||Decrease||Enhances cellular K+ uptake|
|Cell damage||Increase||Intracellular K+ release|
|Succinylcholine||Increase||Cell membrane depolarization|