What is the appropriate management for a patient with hyponatremia?

From the Guidelines

The management of hyponatremia should prioritize treating the underlying cause, with fluid restriction and hypertonic saline administration as needed, while closely monitoring serum sodium levels to prevent overly rapid correction and osmotic demyelination syndrome, as recommended by the most recent guidelines 1. The approach to managing hyponatremia depends on its severity, onset, and underlying cause. For mild to moderate hyponatremia (sodium >120 mEq/L) without symptoms, the focus should be on treating the underlying cause while restricting fluid intake to 1-1.5 L/day.

• Key considerations include:
  • Identifying and addressing the underlying cause of hyponatremia
  • Restricting fluid intake to 1-1.5 L/day for mild to moderate hyponatremia
  • Administering hypertonic saline (3% NaCl) at 1-2 mL/kg/hr for symptomatic or severe hyponatremia (<120 mEq/L)
  • Monitoring serum sodium levels closely to prevent overly rapid correction and osmotic demyelination syndrome For symptomatic or severe hyponatremia (<120 mEq/L), hypertonic saline (3% NaCl) may be administered at 1-2 mL/kg/hr, with the goal of increasing serum sodium by 4-6 mEq/L in the first 24 hours to alleviate acute symptoms, as recommended by the American Association for the Study of Liver Diseases 1.
• Correction should not exceed 8-10 mEq/L in 24 hours or 18 mEq/L in 48 hours to prevent osmotic demyelination syndrome.
• Regular monitoring of serum sodium levels (every 2-4 hours in severe cases) is essential to ensure appropriate correction rates. The treatment approach balances the risks of hyponatremia-induced cerebral edema against those of overly rapid correction, which can cause permanent neurological damage, and should be guided by the most recent and highest-quality evidence, such as the 2021 practice guidance by the American Association for the Study of Liver Diseases 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

The appropriate management for a patient with hyponatremia is treatment with tolvaptan, which has been shown to cause a statistically significant increase in serum sodium levels.

• Key points:
  • Tolvaptan is effective in increasing serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.
  • The treatment should be initiated at a dose of 15 mg once daily, with possible titration to 30 mg once daily, then to 60 mg once daily, until either the maximum dose or normonatremia is reached.
  • Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
  • Patients should be monitored for changes in serum sodium levels, with assessments at 8 hours after study drug initiation and daily up to 72 hours. 2

From the Research

Management of Hyponatremia

The management of hyponatremia depends on the underlying cause, severity, and symptoms of the condition. According to 3, treating the underlying cause is the primary approach for most patients. The following are key considerations in managing hyponatremia:

• Classification: Patients should be categorized based on their fluid volume status into hypovolemic, euvolemic, or hypervolemic hyponatremia 4, 5.
• Symptomatic Hyponatremia: Severely symptomatic hyponatremia is a medical emergency and should be treated with bolus hypertonic saline to increase the serum sodium level by 4-6 mEq/L within 1-2 hours, but not exceeding a correction limit of 10 mEq/L within the first 24 hours 3, 6.
• Treatment Options:
  • Hypovolemic hyponatremia: treated with normal saline infusions 5.
  • Euvolemic hyponatremia: managed by restricting free water consumption, using salt tablets, or intravenous vaptans 4, 5.
  • Hypervolemic hyponatremia: primarily treated by managing the underlying cause (e.g., heart failure, cirrhosis) and restricting free water intake 5, 7.
• Vaptans: Vasopressin receptor antagonists, such as tolvaptan, can be effective in treating euvolemic and hypervolemic hyponatremia, including cases associated with cirrhosis and heart failure 4, 7.
• Rapid Correction: Overly rapid correction of hyponatremia should be avoided to prevent osmotic demyelination syndrome, a rare but severe neurological condition 3, 6.