Hypokalemia – Diagnosis, Symptoms, and Treatment

What is Hypokalemia?

Hypokalemia is an electrolyte disorder characterized by a low serum potassium concentration (<3.5 mg/dL). It can be caused by various conditions such as vomiting, diarrhea, and renal losses due to diuretic medication use (e.g., loop diuretics). Occasionally, it is caused by transcellular potassium shifts resulting from metabolic alkalosis, excessive insulin use, or beta-agonist therapy (e.g., albuterol inhaler).

The clinical features include muscle weakness, renal abnormalities, and glucose intolerance. Severe cases can result in life-threatening cardiac arrhythmias.

What Causes Hypokalemia?

Gastrointestinal or renal losses most frequently cause hypokalemia. Gastrointestinal etiologies include vomiting and diarrhea. Renal losses often occur with diuretic therapy such as thiazide diuretics (e.g., hydrochlorothiazide) or loop diuretics such as Lasix (furosemide) and Bumex (bumetanide). Cellular shifts in potassium may also lead to low potassium and normally results from conditions such as insulin use and beta-agonists (e.g., albuterol). Individuals with primary hyperaldosteronism can also develop hypokalemia as excessive aldosterone levels lead to increased potassium secretion by the kidney.

How Common is Hypokalemia?

Hypokalemia is an exceedingly common electrolyte abnormality often evaluated in both inpatient and outpatient settings. Severe cases that are unresponsive to first-line treatment typically require consultation with a nephrology (kidney) specialist.

Up to approximately 20% of hospitalized patients have low potassium - only about 5% of these patients have clinically significant hypokalemia. In the outpatient setting, an estimated 14% of individuals have evidence of mild hypokalemia. Diuretic use is a frequent cause, occurring in about 80% of individuals taking diuretic therapy.

Signs and Symptoms

Clinical features depend on the degree of hypokalemia and rapidity at which low potassium occurs. Patients with borderline low levels of potassium may be asymptomatic. Similarly, those with chronically low potassium levels may have no symptoms. The most common clinical manifestations of symptomatic hypokalemia include:

• Muscle weakness
• Cardiac arrhythmias
• Renal abnormalities
• Glucose intolerance

Muscle breakdown (rhabdomyolysis) can occur in severe cases. Underlying cardiac issues that predispose to arrhythmia in the setting of hypokalemia include digoxin toxicity, myocardial infarction, and underlying long QT syndrome.

Diagnosis

The diagnosis can be suggested based on symptoms and physical examination but is typically confirmed with laboratory studies. Your doctor will typically begin by obtaining a CMP (comprehensive metabolic panel) – this test evaluates your kidney function and electrolytes (including potassium). Serum potassium levels < 3.5 mg/dL are typically considered hypokalemia in most laboratories. Once the diagnosis has been confirmed, your doctor may ask you specific questions about vomiting, diarrhea, or certain medications such as diuretics. If there is no apparent etiology for the hypokalemia, your doctor will usually obtain additional studies such as a spot urine potassium concentration or a 24-hour urine collection. This is obtained to distinguish kidney losses of potassium versus other forms of potassium loss. They will also typically get other studies such as a complete blood cell count (CBC) and thyroid function studies (TSH, free T4). Thyrotoxic periodic paralysis is an essential consideration in hypokalemic patients.

An electrocardiogram is typically requested to evaluate your heart’s electrical activity and ensure no problematic changes due to hypokalemia. If your potassium is significantly low, you may be hospitalized and receive continuous EKG monitoring (telemetry)

Hypokalemia Medication and Treatment

The treatment of hyperkalemia depends on the severity and underlying cause. Patients with life-threatening hypokalemia require treatment with rapid infusion of intravenous potassium chloride. This is typically administered via a catheter inserted into a large vein, such as the internal jugular or femoral vein. Smaller peripheral veins can become irritated (phlebitis) with rapid infusion of potassium.

Patients with less severe hypokalemia who can tolerate oral medications are often treated with oral potassium chloride.

Occasionally, potassium repletion is not the best treatment for hypokalemia. This is the case with hypokalemia due to thyrotoxic periodic paralysis. This condition results in increased sympathetic nervous system activity, which drives potassium into cells. The treatments for this form of hypokalemia are non-selective beta-blockers, such as Inderal (propranolol). Administration of potassium in these patients can result in rebound hyperkalemia (elevated serum potassium). Similarly, patients with hypokalemia related to low magnesium levels should have magnesium repleted as potassium therapy alone is often insufficient.

Besides potassium chloride formulations, oral potassium is also available as potassium bicarbonate, potassium citrate, potassium acetate, and potassium phosphate. Potassium bicarbonate, potassium citrate, and potassium acetate are typically indicated in hypokalemia and coexisting metabolic acidosis. Potassium phosphate is reserved for patients with hypokalemia and hypophosphatemia due to proximal renal tubular acidosis.

Potassium-sparing diuretics may also be indicated in individuals with urinary potassium loss. This often includes Midamor (amiloride). Individuals with primary aldosteronism typically benefit from treatment with Aldactone (spironolactone) or Inspra (eplerenone). Patients may also be initiated on antihypertensive medications that increase serum potassium, such as ACE inhibitors (e.g., Zestril – Lisinopril) or angiotensin receptor blockers (Cozaar – losartan).

References:

1. Gennari FJ. Hypokalemia. N Engl J Med 1998; 339:451. - https://www.nejm.org/doi/full/10.1056/nejm199808133390707
2. Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000; 160:2429. - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485434
3. Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol 2007; 18:2649. - https://jasn.asnjournals.org/content/18/10/2649