How to manage hyponatremia (low sodium levels) in patients?

From the Guidelines

The management of hyponatremia should prioritize identifying and addressing the underlying cause while carefully correcting sodium levels, with the goal of improving morbidity, mortality, and quality of life. For patients with hyponatremia, the treatment approach depends on the severity and underlying cause of the condition.

• For mild asymptomatic hyponatremia (sodium 130-135 mEq/L), fluid restriction to 800-1000 mL/day is often sufficient 1.
• For moderate to severe symptomatic hyponatremia (sodium <130 mEq/L with neurological symptoms), 3% hypertonic saline may be administered at 1-2 mL/kg/hour, aiming for sodium correction of 4-6 mEq/L in the first 24 hours and not exceeding 8 mEq/L/day to prevent osmotic demyelination syndrome 1.
• For SIADH-induced hyponatremia, fluid restriction plus oral salt tablets (1-2 g three times daily) or vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) may be used 1.
• Hypervolemic hyponatremia often responds to loop diuretics like furosemide (20-40 mg IV or oral) combined with fluid restriction.
• Hypovolemic hyponatremia requires isotonic fluid replacement with 0.9% saline. Regular monitoring of serum sodium every 2-4 hours during active correction is essential, with slower correction rates for chronic hyponatremia (present >48 hours) 1. Addressing underlying conditions such as heart failure, cirrhosis, adrenal insufficiency, or medication effects is crucial for successful long-term management. The most recent and highest quality study 1 provides the best guidance for managing hyponatremia, emphasizing the importance of careful correction of sodium levels and addressing the underlying cause.

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. Patients were randomized to receive either placebo (N = 220) or tolvaptan (N = 223) at an initial oral dose of 15 mg once daily. 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

Treatment of Hyponatremia:

• Tolvaptan can be used to treat hyponatremia (low sodium levels) in patients.
• The initial dose is 15 mg once daily, which can be increased to 30 mg once daily, then to 60 mg once daily, as needed and tolerated.
• Treatment should be maintained for 30 days.
• Key Considerations:
  • Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
  • Patients can resume or initiate fluid restriction as clinically indicated after the first 24 hours.
• Efficacy: Tolvaptan has been shown to cause a statistically significant increase in serum sodium levels compared to placebo in patients with hyponatremia 2.

From the Research

Treatment Approaches for Hyponatremia

The management of hyponatremia involves treating the underlying cause and categorizing patients according to their fluid volume status (hypovolemic, euvolemic, or hypervolemic) 3, 4.

• Hypovolemic hyponatremia is treated with normal saline infusions.
• Euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans.
• Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction.

Management of Severe Hyponatremia

Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency that requires immediate attention 3, 4.

• US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours but by no more than 10 mEq/L (correction limit) within the first 24 hours.
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition.

Role of Vaptans in Hyponatremia Management

Vaptans, such as conivaptan, lixivaptan, and tolvaptan, are vasopressin receptor antagonists that can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure 5, 6, 7.

• Vaptans increase free water excretion without adverse consequences and can be used to treat euvolemic and hypervolemic hyponatremia.
• The use of vaptans appears to be beneficial for patients and physicians due to their efficiency and reliability, but their effects on hard outcomes in patients with heart failure and hyponatremia require further examination.