Hypokalemia

Essentials of Diagnosis

• Serum K⁺ < 3.5 mEq/L (< 3.5 mmol/L)

• Severe hypokalemia may induce arrhythmias and rhabdomyolysis

• Assessment of urine potassium excretion (urine potassium to creatinine ratio) can distinguish renal from non-renal loss of potassium

General Considerations

• Hypokalemia can result from

  • Insufficient dietary potassium intake

  • Intracellular shifting of potassium from the extracellular space

  • Potassium loss (renal or extra-renal)

• A low dietary potassium intake is usually not sufficient to cause hypokalemia because the kidneys can lower urine potassium excretion to very low levels (< 15 mEq/L)

• Shift of potassium into cells is increased by insulin and beta-adrenergic stimulation

• Excess potassium excretion by the kidneys is usually due to increased aldosterone action in the setting of preserved delivery of sodium to the distal nephron

• Magnesium

  • An important regulator of potassium handling

  • Low levels lead to persistent renal excretion of potassium; hypokalemia is often refractory to treatment until the magnesium deficiency is corrected

• Loop diuretics (eg, furosemide) cause substantial renal potassium and magnesium losses

• Usually asymptomatic

• When severe, may lead to muscle weakness and cardiac arrhythmias

• Involvement of gastrointestinal smooth muscle may result in constipation or ileus

• Rhabdomyolysis with associated acute kidney injury may occur with potassium levels < 2.5 mEq/L

• May additionally present as polyuria and polydipsia due to diminished concentrating ability of the kidney (nephrogenic DI)

• Chronic hypokalemia can lead to kidney disease (tubulointerstitial nephritis)

Laboratory Tests

• Transient hypokalemia is generally secondary to intracellular shift, while sustained hypokalemia is secondary to potassium wasting or rarely inadequate intake

• Assessment of renal potassium excretion can help distinguish renal from non-renal causes

• A 24-hour urine collection is the most accurate method for assessing renal handling of potassium, with a level < 25 mEq/day compatible with appropriate renal potassium retention, and higher values corresponding to renal potassium wasting

• A more immediate assessment can be made by measuring a urine potassium to creatinine ratio (U_K/U_Cr) on a spot urine sample

• In the setting of hypokalemia, a U_K/U_Cr ratio < 13 mEq/g (or 1.5 mEq/mmol) is suggestive of a nonrenal etiology, most commonly gastrointestinal losses, intracellular potassium shifts, or inadequate dietary intake; higher values imply renal potassium wasting

Diagnostic Procedures

• Characteristic progression of electrocardiogram (ECG) changes as the hypokalemia becomes more severe: initially T wave flattening, subsequently ST depressions and T wave inversions, ultimately U waves

• Typical ECG patterns may be not be observed in all patients

• Any underlying conditions should be treated and causative drugs discontinued

• Magnesium deficiency should be corrected, particularly in refractory hypokalemia

• Oral potassium supplementation

  • Safest for mild to moderate deficiency

  • However, may cause gastrointestinal upset

  • Dosages

    • 20 mEq/day is generally sufficient to prevent hypokalemia

    • In cases of established hypokalemia, 40–100 mEq/day over a period of days to weeks may be needed to treat hypokalemia and fully replete potassium stores

• Intravenous potassium

  • Reserved for severe hypokalemia (< 3.0 mEq/L)

  • Requires careful monitoring due to the risk of transient hyperkalemia

  • Potassium chloride

    • May be given through a peripheral intravenous line at rates up to 10–15 mEq/h diluted in 0.5% or 0.9% normal saline

    • Higher rates (up to 20 mEq/h) require central access due to the risk of peripheral vein irritation

    • In cases of concurrent metabolic acidosis, potassium repletion should take precedence over alkali administration because correction of the acidosis results in intracellular shift of potassium, further decreasing extracellular potassium concentration

    • Similarly, potassium should be given in a saline, rather than dextrose solution since dextrose would stimulate insulin release and hence, intracellular shift

Follow-Up

• Monitor ECG continuously when infusing intravenous potassium for severe hypokalemia

• Check serum potassium level every 3–6 hours

Complications

• Hypokalemia increases the likelihood of digitalis toxicity

• In patients with heart disease, hypokalemia induced by beta-2-adrenergic agonists and diuretics may impose a substantial risk

Prognosis

• Most hypokalemia will correct with replacement after 24–72 h

When to Refer

• Patients with unexplained hypokalemia, refractory hyperkalemia, or clinical features suggesting alternative diagnoses (eg, aldosteronism or hypokalemic periodic paralysis) should be referred for endocrinology or nephrology consultation

When to Admit

• Patients with symptomatic or severe hypokalemia, especially with cardiac manifestations, require cardiac monitoring, frequent laboratory testing, and potassium supplementation