a. Definition. Hyperkalemia refers to serum potassium concentration >5 mEq/L.
b. Maintenance of plasma potassium
i. Plasma potassium is maintained in a narrow range primarily by two mechanisms:
1. Intracellular fluid (ICF) and extracellular fluid (ECF) shifts of potassium
a. Normal extracellular potassium concentration is 4 mEq/L, and intracellular potassium concentration is 150 mEq/L.
2. Renal potassium excretion
a. Normal potassium is excreted 90% renally and 10% through the gastrointestinal (GI) tract.
ii. Increased potassium shifting to the extracellular space and decreased renal potassium losses lead to hyperkalemia.
iii. Increased potassium intake is rarely associated with hyperkalemia unless a patient is oliguric or has significant kidney disease. (Typically, a glomerular filtration rate [GFR] >20 mL/min is sufficient to maintain potassium balance provided that the diet is not extremely high in potassium.)
B. Clinical Manifestations. Symptoms primarily arise from alterations in membrane polarization.
i. Altered cardiac conduction is the most life-threatening abnormality. This occurs primarily by making the resting membrane potential less negative (e.g., –90 mV to –80 mV).
ii. An electrocardiogram (EKG) may first show peaking of the T wave; then flattening of the P wave and prolongation of the PR interval; then widening of the QRS complex; and finally a deep S wave or sine wave, which heralds ventricular fibrillation and cardiac arrest.
Hyperkalemia with EKG abnormalities is an emergency! When any EKG abnormality is seen, life-threatening arrhythmias can rapidly occur.
b. Neuromuscular. A range of abnormalities from mild weakness to tingling and paraesthesias may occur. Rarely, flaccid paralysis takes place.
c. Renal. Hyperkalemia reduces renal ammoniagenesis and NH4+ secretion, leading to less net acid excretion and metabolic acidosis. The acidosis then worsens the degree of hyperkalemia.
C. Causes of Hyperkalemia
a. Hyperkalemia with transcellular redistribution
i. Acidosis-induced hyperkalemia occurs primarily due to acidosis due to inorganic acids. Cations move intracellularly in exchange for potassium; potassium levels rise about 0.5 mEq/L for every decrease of 0.1 pH units. Respiratory acidosis causes a small rise in serum potassium levels.
Metabolic acidosis from organic acids (e.g., lactic acid) does not typically result in hyperkalemia because both the cation and organic anion are freely permeable across the cell membrane.
ii. Insulin deficiency and hypertonicity (e.g., hyperglycemia) promotes potassium shift from the ICF to the ECF through solvent drag and lack of stimulation of the Na+/K+-ATPase.
iii. β-Adrenergic antagonists, specifically β2 antagonists, cause hyperkalemia but do not lead to life-threatening potassium levels.
iv. Hyperkalemic periodic paralysis is a rare hereditary disorder leading to recurrent weakness or paralysis. Stimuli that lead to mild hyperkalemia (e.g., exercise) can precipitate an episode.
v. Pseudohyperkalemia occurs with redistribution of potassium out of cells after blood is drawn (the laboratory will usually report that the blood sample analyzed was a hemolyzed specimen).
vi. Hemolysis and rapid tissue breakdown in conditions such as rhabdomyolysis or tumor lysis cause release of intracellular potassium.
b. Decreased potassium excretion
i. Kidney disease. GFR <15 mL/min can be accompanied by hyperkalemia, whereas GFR >20 mL/min rarely leads to hyperkalemia.
Patients with significant kidney dysfunction must be educated about the high potassium content of certain foods, such as citrus fruits and juices, tomatoes, potatoes, and salt substitutes.
ii. Renal secretory defects associated with interstitial nephritis, sickle cell disease, obstructive uropathy, and renal transplantation all may lead to distal renal tubular defects and hyperkalemia.
1. Heparin, regardless of molecular weight, suppresses aldosterone excretion.
2. Spironolactone, triamterene, and trimethoprim inhibit potassium excretion by sodium channels in the distal nephron.
3. Angiotensin-converting enzyme inhibitors suppress aldosterone production.
4. Nonsteroidal antiinflammatory drugs cause a reversible form of hyporeninemic hypoaldosteronism.
5. Cyclosporine and tacrolimus also cause renal potassium secretory defects.
iv. Mineralocorticoid deficiency leads to a hyperchloremic metabolic acidosis and hyperkalemia. Causes include Addison’s disease and hyporeninemic hypoaldosteronism, as seen in patients with type 4 renal tubular acidosis (see Chapter 40) from diabetes mellitus or AIDS.
D. Approach to the Patient
a. History can be helpful in determining new or changed medications and dietary changes.
b. Laboratory analysis
i. Serum tests include complete blood count (CBC) and lactate dehydrogenase (LDH) levels to assess for hemolysis, creatine kinase (CK) to assess for rhabdomyolysis, arterial blood gases (ABG) to assess for acidosis, metabolic panel to assess renal function and serum glucose, and osmolality for assessment of transtubular potassium gradient (TTKG) (see Chapter 45). Cortisol, renin, and aldosterone levels can be measured but are rarely needed.
ii. Urine tests include sodium to assess volume status, potassium, and osmolality to calculate TTKG (which should be greater than 10 in hyperkalemia).
E. Treatment. As with hypokalemia, the underlying disorder, if known, should be treated along with the serum potassium level. Always ask if a laboratory specimen was hemolyzed. The potassium level should be confirmed with a repeat blood draw, particularly in patients who do not have symptoms, by measuring plasma levels rather than serum. This avoids the leakage of potassium out of cells in the course of clotting.
a. Antagonism of cardiac conduction abnormalities can be accomplished with the administration of calcium.
i. Give 10 mL of 10% calcium gluconate administered by intravenous (IV) route over 2–3 minutes.
ii. The onset of action is minutes, and the effect lasts for up to 1 hour. Repeat as needed; continuous calcium infusions are occasionally required.
iii. Works by raising the threshold for depolarization (e.g., –75 mV to –65 mV) and restoring the normal difference between resting potential and threshold potential.
Intravenous calcium does not lower serum potassium levels, but this therapy should be used whenever there is EKG evidence of hyperkalemia-induced changes to prevent arrhythmias.
b. Intracellular shifting of potassium occurs relatively rapidly.
i. Insulin and albuterol begin to act over 15–30 minutes, lasting from 4–6 and 2–4 hours, respectively.
ii. Bicarbonate distributes potassium into cells and may help chronic hyperkalemia; however, efficacy of this therapy to correct acute hyperkalemia is unclear.
c. Potassium removal can be accomplished in several ways.
i. Loop or thiazide diuretics (e.g., 40–160 mg of furosemide, preferably IV) is given if the patient is making urine.
ii. Sodium polystyrene sulfonate (Kayexalate) is an ion-exchange binding resin that administers a sodium load in exchange for binding potassium.
iii. Newer agents such as patiromer and sodium zirconium cyclosilicate have been developed to enhance GI elimination of potassium and have been studied for more chronic therapy of hyperkalemia, but are not yet approved by the Food and Drug Administration (FDA).
iv. Hemodialysis and peritoneal dialysis result in the extracorporeal removal of potassium. As much as 300 mEq of potassium can be removed during each treatment, and this is by far the most effective treatment of hyperkalemia in the setting of renal failure.
d. Limiting potassium intake is an important step for patients who have an irreversible reduction in potassium elimination such as chronic kidney disease. Dietary education can help patients to avoid high potassium foods.
Suggested Further Readings
Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med 2005;20:272–90.Find this resource:
Ingelfinger JR. A new era for the treatment of hyperkalemia? N Engl J Med 2014;372:275–7.Find this resource: