How do you investigate and manage hyponatremia?

From the Guidelines

For a patient with hyponatremia of 126, the most appropriate management is to monitor and restrict water intake to 1,000 mL/day, as this level is considered mild hyponatremia and does not require specific management apart from monitoring and water restriction, according to the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.

Key Considerations

• Assess the patient clinically for volume status (hypovolemic, euvolemic, or hypervolemic) and measure serum sodium, osmolality, and urine sodium and osmolality.
• For severe symptomatic hyponatremia (sodium <120 mmol/L with seizures or altered consciousness), consider administering 3% hypertonic saline.
• Correction should not exceed 8-10 mmol/L in 24 hours to prevent osmotic demyelination syndrome.

Management Approach

• 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 1.
• For severe hyponatremia (<120 mEq/L), a more severe restriction of water intake with albumin infusion is recommended 1.

Medications and Interventions

• Vasopressin receptor antagonists, such as tolvaptan, can be considered for short-term use (≤30 days) in patients with cirrhosis and hyponatremia, but should be used with caution 1.
• Hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant 1.

Monitoring and Prevention

• Regular monitoring of serum sodium (every 2-4 hours initially for severe cases) is essential to ensure appropriate correction rates and prevent complications.
• Discontinue medications that may cause hyponatremia, such as thiazide diuretics, SSRIs, or carbamazepine.

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.

To investigate and manage hyponatremia, the following steps can be taken:

• Assess the underlying cause of hyponatremia, such as heart failure, liver cirrhosis, or SIADH.
• Monitor serum sodium levels closely, especially in the first 24 hours of therapy.
• Avoid fluid restriction if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
• Consider treatment with tolvaptan, which has been shown to cause a statistically greater increase in serum sodium compared to placebo in patients with euvolemic or hypervolemic hyponatremia.
• Titrate the dose of tolvaptan as needed to achieve normonatremia (serum sodium >135 mEq/L), with a maximum dose of 60 mg once daily.
• Maintain treatment for 30 days, with additional serum sodium assessments on Days 11,18,25, and 30.
• Resume previous therapies for hyponatremia after discontinuation of tolvaptan and reevaluate 7 days later 2.

From the Research

Investigation of Hyponatremia

• The first step in investigating hyponatremia is to determine the severity of the condition, with a sodium concentration of 126 mEq/L considered moderate hyponatremia 3.
• It is essential to identify the underlying cause of hyponatremia, which can include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise 3.
• The patient's volume status should be assessed to determine if they are hypovolemic, euvolemic, or hypervolemic, as this will guide treatment decisions 3, 4.

Management of Hyponatremia

• Treatment of hyponatremia depends on the severity of the condition, the underlying cause, and the patient's volume status 3, 4.
• For patients with severe hyponatremia (sodium concentration < 125 mEq/L) and severe symptoms, emergency infusions with 3% hypertonic saline may be necessary 3.
• For patients with mild or moderate hyponatremia, treatment options include:
  • Hypovolemic hyponatremia: normal saline infusions 3.
  • Euvolemic hyponatremia: restricting free water consumption or using salt tablets or intravenous vaptans 3, 5, 6.
  • Hypervolemic hyponatremia: managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction 3, 4.
• Vasopressin receptor antagonists, such as tolvaptan, lixivaptan, and conivaptan, are promising new therapeutic options for the treatment of hyponatremia, particularly in patients with euvolemic or hypervolemic hyponatremia 7, 4, 5, 6.