What are the treatment options for hyponatremia?

From the Guidelines

Treatment of hyponatremia should be guided by the severity, cause, and symptoms of the condition, with the goal of correcting serum sodium levels at a rate of 4-6 mEq/L per 24-hour period to prevent osmotic demyelination syndrome, as recommended by the American Association for the Study of Liver Diseases in 2021 1.

Overview of Treatment Options

• For mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms, no specific management is required apart from monitoring and water restriction 1.
• For moderate hyponatremia (120-125 mEq/L), water restriction to 1,000 mL/day and cessation of diuretics is recommended, while severe hyponatremia (<120 mEq/L) requires a more severe restriction of water intake with albumin infusion 1.
• Vasopressin receptor antagonists can be used with caution for a short term (≤30 days) to raise serum sodium in cirrhosis, but their use should be carefully considered due to potential risks 1.

Aggressive Intervention for Symptomatic Hyponatremia

• Hypertonic (3%) saline may be administered intravenously at 1-2 mL/kg/hour for short-term treatment of patients with symptomatic or severe hyponatremia, or those with imminent liver transplant, with careful monitoring to avoid correcting sodium levels too quickly 1.
• The goal rate of increase of serum sodium is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period to ameliorate the risk of osmotic demyelination syndrome, as recommended by the American Association for the Study of Liver Diseases in 2021 1.

Importance of Addressing Underlying Causes

• Underlying causes of hyponatremia, such as heart failure or liver disease, must be addressed simultaneously with treatment of hyponatremia, including discontinuing offending medications, treating infections, or managing underlying conditions 1.
• Regular monitoring of serum sodium, typically every 2-4 hours during acute correction, is essential to ensure appropriate correction rates and prevent complications, as emphasized by the European Association for the Study of the Liver in 2018 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.

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

The treatment options for hyponatremia include tolvaptan, which can be administered orally at an initial dose of 15 mg once daily, with possible increases to 30 mg once daily and then to 60 mg once daily until normonatremia is reached or the maximum dose is attained 2. Fluid restriction may also be implemented as clinically indicated, with the goal of avoiding overly rapid correction of serum sodium levels 2. It is essential to monitor serum sodium levels to prevent hypernatremia and adjust the treatment plan accordingly 2.

From the Research

Treatment Options for Hyponatremia

The treatment of hyponatremia depends on the underlying cause, severity, and symptoms of the condition. The following are some of the treatment options:

• Treating the underlying cause of hyponatremia, such as correcting heart failure or stopping medications that may be contributing to the condition 3
• Fluid restriction, which is often the first-line treatment for chronic hyponatremia 4, 5
• Hypertonic saline, which is used to treat severely symptomatic hyponatremia, such as in patients with seizures or coma 3, 5, 6
• Urea, which can be used to treat the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure 3, 4
• Vaptans, which are vasopressin receptor antagonists that can be used to treat hyponatremia, particularly in patients with heart failure or the syndrome of inappropriate antidiuresis 3, 4
• Loop diuretics, which can be used to increase renal free water excretion and treat hyponatremia 5

Considerations for Treatment

When treating hyponatremia, it is essential to consider the following:

• The rate of correction of serum sodium levels, as overly rapid correction can cause osmotic demyelination, a rare but severe neurological condition 3, 4
• The need for fluid restriction, which can be challenging for patients, particularly those with heart failure 4, 5
• The potential side effects of medications, such as urea and vaptans, which can include poor palatability, gastric intolerance, and increased thirst 3, 4
• The importance of monitoring serum sodium levels closely, particularly in the first 24 hours of treatment, to avoid overly rapid correction 4, 6

Special Considerations for Severe Hyponatremia

Severely symptomatic hyponatremia, such as in patients with seizures or coma, requires immediate treatment with hypertonic saline to prevent neurological complications 3, 5, 6. The goal of treatment is to increase serum sodium levels by 4-6 mEq/L within 1-2 hours, but not to exceed a correction limit of 10 mEq/L within the first 24 hours 3.