Hypokalemia

Hypokalemia (low serum potassium) is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or diuretic medication). Mild hypokalemia may be asymptomatic or cause mild nonspecific symptoms such as nausea, muscle weakness, and fatigue. Severe deficiency can cause cardiac arrhythmias and death. Treatment consists of oral or IV supplementation in conjunction with treatment of the underlying cause. In concurrent hypomagnesemia, which may lead to refractory hypokalemia, the simultaneous repletion of magnesium and potassium is necessary.

See also “Hyperkalemia”.

• Serum potassium (K⁺) level < 3.5 mEq/L ^[1]
• Severe hypokalemia: K⁺ level < 2.5 mEq/L

Hypokalemia is most often caused by renal or gastrointestinal potassium loss. Other electrolyte imbalances (e.g., hypomagnesemia), alkalosis, and several medications can also have an impact on potassium homeostasis.

• Potassium is an important factor in maintaining the resting membrane potential.
• ↓ Extracellular K⁺ concentration → resting membrane potential becomes more negative than -90 mV) → ↓ excitability ^[3]
• Alkalosis can impact potassium balance via intracellular shifts and vice versa.
  • Alkalosis → ↓ extracellular H⁺ → stimulation of the Na⁺/H⁺ antiporter (transfers H⁺ out of the cells in exchange for Na⁺) → ↑ intracellular Na⁺ → ↑ sodium gradient stimulates the Na⁺/K⁺-ATPase (transfers K⁺ into the cells in exchange for Na⁺) → ↓ extracellular K⁺ concentration
  • Hypokalemia → ↓ extracellular K⁺ concentration → ↓ potassium gradient inhibits the Na⁺/K⁺-ATPase → ↓ extracellular Na⁺ → ↓ sodium gradient inhibits the Na⁺/H⁺ antiporter → ↓ extracellular H⁺ → alkalosis
  • Exception: In renal tubular acidosis, findings include hypokalemia and metabolic acidosis!

K⁺ acts like H⁺: Hypokalemia leads to alkalosis and vice versa!

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

• Hypomagnesemia can impact potassium balance via the following mechanisms of increased renal loss: ^[4]
  • Magnesium serves as a cofactor in Na⁺/K⁺-ATPases → hypomagnesemia disrupts the Na⁺/K⁺-ATPase in the basolateral membrane of the proximal convoluted loop of Henle → ↓ Na⁺ reabsorption → ↑ luminal Na⁺ → ↑ Na⁺ reabsorption and ↑ K⁺ secretion by the principal cells distally
  • Apical ROMK channels in principal cells are inhibited by intracellular magnesium. With low levels of magnesium available, the ROMK channels are not inhibited, resulting in increased K⁺ secretion.

Hypomagnesemia can lead to refractory hypokalemia!

Patients may be asymptomatic, particularly if the deficiency is mild. Symptoms usually occur if serum K⁺ levels are < 3.0 mEq/L and/or decrease rapidly. ^[2]

• Cardiovascular manifestations
  • Symptoms of cardiac arrhythmias (e.g., palpitations, irregular pulse, syncope)
  • Hypotension
• Neuromuscular manifestations
  • Muscle cramps and spasms ^[5]
  • Muscle weakness, paralysis
  • Respiratory failure secondary to paralysis of the respiratory muscles
  • Rhabdomyolysis
  • Decreased deep tendon reflexes
• Gastrointestinal manifestations
  • Nausea, vomiting ^[5]
  • Constipation or ileus
  • Fatigue
• Other manifestations
  • Hyperglycemia ^[6]
  • Polyuria ^[7]
  • Symptoms of underlying causes, including:
    • Dehydration in gastroenteritis
    • Tachycardia and tremors in alcohol withdrawal
    • Symptoms of thyrotoxicosis
    • Symptoms of digoxin toxicity in patients treated with digoxin ^[8]

Hypokalemia (and hyperkalemia) can cause cardiac arrhythmia and may lead to ventricular fibrillation!

All patients require an ECG and laboratory studies to confirm the diagnosis and rule out concurrent electrolyte abnormalities. Further diagnostic tests depend on the suspected underlying etiology.

Initial evaluation

Laboratory studies ^[1]

• Electrolytes and kidney function
  • Serum K⁺ levels
  • Basic metabolic panel
  • Serum calcium, magnesium, phosphate
• Blood gas (venous or arterial): : may show metabolic alkalosis
• Urinary potassium: Consider measuring to narrow down underlying etiology ^[9][10][11]
  • Methods
    • Spot urine: rapid assessment, indicated in urgent cases , less reliable than 24-hour collections
    • 24-hour urine collection: less practical, indicated for chronic cases and uncertain diagnoses, more accurate than spot urine
  • Findings
    • Renal loss; : spot urine > 15–20 mEq/L (24 hour collection > 15 mEq/L) ^[1][10]
    • Extrarenal loss; : spot urine < 15–20 mEq/L (24 hour collection < 15 mEq/L) ^[11]

Consider confirming abnormal serum potassium levels with a repeat blood draw.

ECG findings in hypokalemia ^[2][12]

• Mild to moderate hypokalemia
  • T-wave flattening or inversion
  • ST depression
  • Prolonged PR interval
• Moderate to severe hypokalemia
  • Presence of U waves: small waveform following the T wave that is often absent but becomes more pronounced in hypokalemia or bradycardia ^[2]
  • T and U wave fusion
  • QT prolongation ^[12]
• Dysrhythmias
  • Premature atrial and ventricular complexes
  • Sinus bradycardia
  • Paroxysmal atrial or junctional tachycardia
  • Ventricular dysrhythmias, e.g., Torsades de pointes
  • PEA/asystole

To remember that low potassium may result in a flattened T wave, think of: "No pot, no tea (T)!"

Identification of underlying etiology

• If the etiology is still unclear, further testing can help determine the underlying etiology.
• Imaging is not routinely required but may be necessary if certain underlying etiologies are suspected. ^[1]

Approach

Most patients require potassium chloride (KCl) repletion, management of concurrent electrolyte abnormalities (see “Electrolyte repletion”), and treatment of the underlying cause. See “Potassium replacement” for detailed repletion regimens for hypokalemia, treatment goals, warnings, and adverse effects.

• Severe hypokalemia (< 2.5 mEq/L) and/or high risk of recurrent severe hypokalemia
  • KCl: High-dose IV repletion
  • Consider admission to ICU, continuous cardiac monitoring, and central line placement.
• Moderate hypokalemia (2.5–2.9 mEq/L)
  • KCl: Oral or IV repletion may be used.
  • Disposition usually determined by treatment of underlying disorder
• Mild hypokalemia with easily reversible cause (3.0–3.5 mEq/L)
  • Prioritize treatment of the underlying condition (e.g., GI fluid losses).
  • Consider oral supplementation.
  • Consider increasing dietary potassium intake. ^[14]
  • Patients can usually be discharged after stabilization.

IV potassium may cause local irritation and lead to cardiac arrhythmias. Therefore, it should always be administered slowly (max. rate of 10 mEq/hour via a peripheral line or 40 mEq/hour via a central line)

Treatment of underlying condition

• Diuretic-induced hypokalemia (e.g., loop diuretics or thiazides) ^[1]
  • Discontinue the diuretic or reduce the dose and combine with potassium-sparing diuretics, e.g., spironolactone.
  • Rehydrate with normal saline if the patient has both volume depletion and contraction alkalosis.
• Oral or IV magnesium for patients with hypomagnesemia
• For other underlying conditions, see “Etiology of hyperkalemia”.

Potassium supplementation will be ineffective if concurrent hypomagnesemia is left untreated (see “Magnesium repletion”).

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