What is the treatment for persistent hypo-osmolar hyponatremia (low sodium levels in the blood)?

From the Guidelines

To treat persistent hypo-osmolar hyponatremia, first identify and address the underlying cause while carefully correcting sodium levels, with the most recent guidelines suggesting fluid restriction and vaptans as primary treatment options 1.

Treatment Approach

For mild to moderate cases (sodium >120 mEq/L) with minimal symptoms,

• fluid restriction to 800-1000 mL/day is the initial approach, as it can help prevent further decrease in serum sodium levels 1.
• Consider oral urea (15-30 g daily) or tolvaptan starting at 15 mg daily (maximum 60 mg daily), monitoring sodium levels closely, especially in cases of SIADH 1.

Severe Symptomatic Hyponatremia

For severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms),

• administer 3% hypertonic saline as a 100-150 mL bolus over 10-20 minutes, repeatable up to 2-3 times if symptoms persist, aiming for a sodium correction rate of 4-6 mEq/L in the first 24 hours and not exceeding 8 mEq/L/day to prevent osmotic demyelination syndrome 1.

Monitoring and Discontinuation

Regular monitoring of serum sodium (every 2-4 hours initially for severe cases, then every 4-6 hours) is essential to ensure appropriate correction rates. Discontinue treatment when symptoms improve or sodium reaches safe levels (>120 mEq/L).

Key Considerations

• The treatment of hypovolemic hyponatremia consists of administration of sodium together with identification of the causative factor (usually excessive diuretic administration) 1.
• Vaptans, such as tolvaptan, have been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH, heart failure, or cirrhosis 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 dose of tolvaptan could be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) was reached Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies

The treatment for persistent hypo-osmolar hyponatremia is tolvaptan. The initial oral dose is 15 mg once daily, which can be increased to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) is reached 2.

• Key points:
  • Tolvaptan can be used to treat euvolemic or hypervolemic hyponatremia.
  • The dose of tolvaptan can be titrated to achieve the desired serum sodium level.
  • Tolvaptan has been shown to be effective in increasing serum sodium levels in patients with hyponatremia.

From the Research

Treatment Options for Hypo-Osmolar Hyponatremia

• Fluid restriction is a common treatment approach for euvolemic hyponatremia, as seen in the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3, 4, 5.
• Hypertonic saline can be used to treat severe symptomatic hyponatremia 3, 5, 6.
• Vasopressin receptor antagonists, also known as vaptans, have been introduced as a specific and direct therapy for SIADH and other forms of euvolemic and hypervolemic hyponatremia 3, 4, 6, 7.
• Loop diuretics can be useful in reducing water retention in patients with hypervolemic hyponatremia, but may exacerbate hyponatremia if not used carefully 6.
• Demeclocycline, lithium carbonate, and urea are other pharmacologic agents that have been used to treat hyponatremia, but may have significant limitations and side effects 3, 4, 6.

Considerations for Treatment

• It is essential to limit the daily increase of serum sodium to less than 8-10 mmol/liter to avoid osmotic demyelination 3.
• The first 24 hours of vaptan treatment are critical for preventing an overly rapid correction of hyponatremia, and serum sodium should be measured frequently 3.
• Discontinuation of vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse, and it may be necessary to taper the vaptan dose or restrict fluid intake 3.