Hypokalemia

GENERAL PRINCIPLES

• Hypokalemia is defined as a plasma [K⁺] [K⁺] by the total daily urine output. A spot urine [K⁺] may be helpful (urine [K⁺] 5.0 mEq/L.

• Pseudohyperkalemia represents an artificially elevated plasma [K⁺] due to K⁺ movement out of cells immediately before or following venipuncture. Contributing factors include repeated fist clenching, hemolysis, and marked leukocytosis or thrombocytosis.

• True hyperkalemia occurs as a result of one of the following:

î Transcellular shift. Insulin deficiency, hyperosmolality, nonselective β-blockers, digitalis, metabolic acidosis (excluding those from organic acids), and depolarizing muscle relaxants, such as succinylcholine, release K⁺ from ICF stores into the ECF compartment. The release of intracellular K+ can also be seen after severe exercise, rhabdomyolysis, and tumor lysis syndrome.

î Increased exposure to K⁺ is rarely the sole cause of hyperkalemia unless there is an impairment in renal excretion. Foods with a high content of K⁺ include salt substitutes, dried fruits, nuts, tomatoes, potatoes, spinach, bananas, and oranges. Juices derived from these foods may be especially rich sources.

î Decreased renal K⁺ excretion. In the setting of hyperkalemia, the kidney is capable of generating a significant urinary excretion of K⁺. This process can be impaired by a number of processes, including volume depletion, renal injury, adrenal insufficiency, and hyporeninemic hypoaldosteronism (type 4 RTA).

• Drugs may also be implicated in the genesis of hyperkalemia through a variety of mechanisms. Common culprits include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, NSAIDs, and cyclosporine.

DIAGNOSIS

Clinical Presentation

• The most serious effect of hyperkalemia is cardiac arrhythmogenesis secondary to potassium’s pivotal role in membrane potentials. Patients may present with palpitations, syncope, or even sudden cardiac death.

• Severe hyperkalemia causes partial depolarization of the skeletal muscle cell membrane and may manifest as weakness, potentially progressing to flaccid paralysis and hypoventilation if the respiratory muscles are involved.

Diagnostic Testing

• If the etiology is not readily apparent and the patient is asymptomatic, pseudohyperkalemia should be excluded by rechecking laboratory data.

• An assessment of renal [K⁺ ] excretion and the renin-angiotensin-aldosterone axis can help narrow the differential diagnosis when the etiology is not immediately apparent.

î Low aldosterone levels suggest either adrenal disease (renin levels elevated) or hyporeninemic hypoaldosteronism (renin levels low; occurs with type 4 RTA).

î High aldosterone levels, typically accompanied by high renin levels, suggest aldosterone resistance (pseudohypoaldosteronism) but can also be seen in K⁺-sparing diuretics.

• ECG changes include increased T-wave amplitude or peaked T waves. More severe degrees of hyperkalemia result in a prolonged PR interval and QRS duration, atrioventricular conduction delay, and loss of P waves. Progressive widening of the QRS complex and its merging with the T wave produce a sine wave pattern. The terminal event is usually ventricular fibrillation or asystole.

TREATMENT

Severe hyperkalemia with ECG changes is a medical emergency and requires immediate treatment directed at minimizing membrane depolarization and acutely reducing the ECF [K⁺]. Acute therapy may consist of some or all of the following (the hypokalemic effect is additive):

• Calcium gluconate decreases membrane excitability but does not lower [K⁺].

• Insulin causes K⁺ to shift into cells and temporarily lowers the plasma [K⁺]. A commonly used combination is 10-20 units of regular insulin and 25-50 g of glucose administered IV Hyperglycemic patients should be given the insulin alone.

• NaHCO₃ is effective for severe hyperkalemia associated with metabolic acidosis. In the acute setting, it can be given as an IV isotonic solution (three ampules of NaHCO₃ in 1 L of 5% dextrose).

• β₂-Adrenergic agonists promote cellular uptake of K⁺. The onset of action is 30 minutes, lowering the plasma [K⁺] by 0.5-1.5 mEq/L, and the effect lasts for 2-4 hours. Albuterol can be administered in a dose of 10-20 mg as a continuous nebulized treatment over 30-60 minutes.

• Longer term means for [K⁺] removal.

î Increasing distal Na⁺ delivery in the kidney enhances renal K⁺ clearance. This can be achieved with the administration of saline in patients who appear volume depleted. Otherwise, diuretics can be used if renal function is adequate.

î Cation exchange resins, such as sodium zirconium cyclosilicate and patiromer, promote the excretion of K⁺ in the GI tract and can be used in the management of chronic or resistant hyperkalemia. Both agents appear to be effective, well tolerated, and safe. The usual dose of patiromer is 8.4 g mixed with 100 mL of water, given daily. Sodium zirconium cyclosilicate may have a faster onset of action and is usually initiated at 10 g up to three times/day.

• Dialysis should be reserved for patients with renal failure and those with severe life-threatening hyperkalemia who are unresponsive to more conservative measures.

• Chronic therapy may involve dietary modifications to avoid high K⁺ foods, correction of metabolic acidosis with oral alkali, the promotion of kaliuresis with diuretics, and/or administration of exogenous mineralocorticoid in states of hypoaldosteronism.