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

From the Guidelines

Hyponatremia should be treated based on its severity, onset speed, and underlying cause, with the goal of correcting serum sodium levels without exceeding 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment approach for hyponatremia depends on the type and severity of the condition. For hypovolemic hyponatremia, fluid resuscitation with saline solution and correction of the causative factor are necessary 1. In cases of hypervolemic hyponatremia, fluid restriction, reduction or discontinuation of diuretics and laxatives, administration of hyperoncotic albumin, and/or vasopressin receptor antagonists ("vaptans") may be used 1.

Medications

Medications like tolvaptan (starting at 15 mg daily) may be used for euvolemic or hypervolemic hyponatremia, while fludrocortisone (0.1 mg daily) can help with hypovolemic states 1. However, the use of these medications should be cautious, especially in patients with liver cirrhosis or impaired liver function, due to the risk of liver dysfunction 1.

Monitoring

Frequent monitoring of serum sodium (every 2-4 hours initially for severe cases) is essential to ensure appropriate correction rates and prevent complications like osmotic demyelination syndrome 1.

Key Considerations

• The underlying cause of hyponatremia must be addressed simultaneously, including discontinuing offending medications, treating SIADH, managing heart failure, or correcting adrenal insufficiency.
• The risk of osmotic demyelination syndrome should be carefully considered when correcting serum sodium levels, especially in patients with chronic hyponatremia.
• The use of vaptans, such as tolvaptan, should be cautious, especially in patients with liver cirrhosis or impaired liver function, due to the risk of liver dysfunction.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Hyponatremia 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 was effective in patients with serum sodium levels <135 mEq/L, <130 mEq/L, and <125 mEq/L.
• The effect of tolvaptan was seen across all disease etiology subsets, including heart failure, liver cirrhosis, and SIADH 2.

From the Research

Definition and Prevalence of Hyponatremia

• Hyponatremia is defined as a serum sodium level of less than 135 mEq/L 3, 4, 5, 6
• It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3, 4, 5, 6

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, 5, 6
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3

Diagnosis and Management of Hyponatremia

• Clinicians should categorize patients according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3, 4, 5, 6
• The approach to managing hyponatremia should consist of treating the underlying cause 3, 4, 5, 6
• 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, 5, 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 Options for Hyponatremia

• Vasopressin receptor antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia 5, 7
• Conivaptan, lixivaptan, and tolvaptan are examples of vasopressin receptor antagonists that have been shown to be safe and effective in clinical trials 5, 7
• Hypertonic saline is reserved for patients with severely symptomatic hyponatremia 3, 4