What are the causes and treatments of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia should be treated with caution, prioritizing the correction rate to prevent osmotic demyelination syndrome, and the most recent guidelines recommend a correction rate of 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period 1.

Treatment Approach

The treatment of hyponatremia depends on the severity, symptoms, and underlying cause. For mild to moderate cases (sodium 125-134 mEq/L), fluid restriction to 800-1000 mL/day is often the first approach.

• For symptomatic or severe hyponatremia (sodium <125 mEq/L), 3% hypertonic saline may be administered intravenously at 1-2 mL/kg/hour, with careful monitoring to avoid correcting sodium levels too quickly.
• The correction rate should not exceed 8-10 mEq/L in the first 24 hours and 18 mEq/L in 48 hours to prevent osmotic demyelination syndrome, as recommended by recent guidelines 1.

Underlying Cause

Addressing the underlying cause is crucial, whether it's medication adjustment, treating heart failure, or managing adrenal insufficiency.

• Regular monitoring of serum sodium, fluid status, and neurological symptoms is essential during treatment.
• Hyponatremia occurs when water and sodium balance is disrupted, either from excessive water retention or sodium loss, affecting cellular function particularly in the brain where it can cause symptoms ranging from headache and nausea to seizures and coma in severe cases.

Specific Considerations

For patients with cirrhosis, the use of vasopressin receptor antagonists can raise serum sodium during treatment, but they should be used with caution only for a short term (≤30 days) 1.

• The use of hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant.
• In cases of hypervolemic hyponatremia, discontinuation of intravenous fluid therapy and free water restriction should be considered, as recommended by guidelines 1.

From the FDA Drug Label

In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies

• Tolvaptan is effective in treating hyponatremia by increasing serum sodium levels.
• The studies showed a statistically significant increase in serum sodium levels in patients treated with tolvaptan compared to placebo.
• Tolvaptan is indicated for the treatment of euvolemic or hypervolemic hyponatremia.
• The medication can be used to treat hyponatremia caused by various underlying conditions, including heart failure, liver cirrhosis, and SIADH 2.

From the Research

Definition and Prevalence of Hyponatremia

• Hyponatremia is defined as a serum sodium concentration <135 mmol/l 3, 4, 5
• It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3
• Hyponatremia can lead to a wide spectrum of clinical symptoms, from mild to severe or even life-threatening, and is associated with increased mortality, morbidity, and length of hospital stay 3, 5

Symptoms and Signs of Hyponatremia

• Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma) 3, 4
• The severity of hyponatremia-induced neurological manifestation and the risk of poor outcome is mainly driven by the rapidity of serum sodium decrease 4
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3

Diagnosis and Management of Hyponatremia

• The approach to managing hyponatremia should consist of treating the underlying cause 3
• Clinicians should categorize patients according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3
• Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 3, 6, 7
• Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency and should be treated with bolus hypertonic saline 3, 4

Treatment of Hyponatremia

• The treatment of hyponatremia should be guided by symptom severity and the assumed onset of hyponatremia development, distinguishing acute (<48 hours) versus chronic hyponatremia (>48 hours) 4
• Vasopressin-2 receptor antagonists (vaptans) provide a new approach to the treatment of hyponatremia and have been shown to be effective in clinical trials 6, 7
• The use of vaptans can lead to aquaresis, an electrolyte-sparing excretion of free water, that results in the correction of serum sodium concentration 7