What is the management of hyponatremia (low sodium levels)?

From the Guidelines

The management of hyponatremia should prioritize correction of the underlying cause, with fluid restriction and vasopressin receptor antagonists being key components of treatment, particularly in cases of hypervolemic states, as evidenced by the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.

Key Considerations

• For mild to moderate hyponatremia (sodium >125 mEq/L), fluid restriction to 800-1000 mL/day is often the first step, particularly in cases of SIADH or hypervolemic states.
• For severe hyponatremia (<125 mEq/L) with neurological symptoms, 3% hypertonic saline should be administered at 100-150 mL over 10-20 minutes, which can be repeated until symptoms improve, as recommended by the guidelines on the management of ascites in cirrhosis 1.
• The correction rate should not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, with a goal rate of increase of serum sodium of 4-6 mEq/L per 24-hour period, as stated in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.

Treatment Approaches

• Vasopressin receptor antagonists such as tolvaptan (starting at 15 mg daily) are effective for euvolemic or hypervolemic hyponatremia but require careful monitoring, as they can raise serum sodium during treatment but should be used with caution only for a short term (≤30 days) 1.
• Treating the underlying cause is essential, including discontinuing offending medications, managing heart failure, correcting adrenal insufficiency with hydrocortisone, or addressing hypothyroidism with levothyroxine.
• Volume status assessment is crucial for appropriate management, as hypovolemic patients require isotonic fluid replacement while hypervolemic patients benefit from fluid restriction and diuretics, as noted in the guidelines on the management of ascites in cirrhosis 1.

Monitoring and Prevention

• Regular monitoring of serum sodium levels every 2-4 hours during correction is necessary to prevent overcorrection, with a focus on preventing osmotic demyelination syndrome.
• Severe hyponatremia (<120 mEq/L) at the time of liver transplantation increases the risk of osmotic demyelination syndrome, and multidisciplinary coordinated care may mitigate this risk, as stated in 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 management of hyponatremia includes the use of tolvaptan, which has been shown to increase serum sodium levels in patients with euvolemic or hypervolemic hyponatremia. Key points to consider when managing hyponatremia with tolvaptan include:

• Initial dose: 15 mg once daily, which can be increased to 30 mg once daily, then to 60 mg once daily, until either the maximum dose or normonatremia is reached
• Fluid restriction: to be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium
• Monitoring: serum sodium concentrations should be determined at 8 hours after study drug initiation and daily up to 72 hours, and additional assessments on Days 11,18,25, and 30 2

From the Research

Management of Hyponatremia

The management of hyponatremia involves treating the underlying cause of the condition, and the approach may vary depending on the severity and symptoms of the patient 3, 4, 5, 6.

• For most patients, the management of hyponatremia should consist of treating the underlying cause, such as heart failure or syndrome of inappropriate antidiuresis (SIAD) 3.
• Urea and vaptans can be effective treatments for SIAD and hyponatremia in patients with heart failure, but have adverse effects such as poor palatability and gastric intolerance with urea, and overly rapid correction of hyponatremia and increased thirst with vaptans 3, 7.
• Severely symptomatic hyponatremia, characterized by signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress, is a medical emergency that requires urgent treatment with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 5, 6.
• The goal of treatment is to increase the serum sodium level 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 to avoid osmotic demyelination syndrome 3, 5, 6.

Treatment Options

The treatment options for hyponatremia include:

• Hypertonic saline for severely symptomatic patients 3, 5, 6
• Urea and vaptans for patients with SIAD and heart failure 3, 7
• Water restriction for patients with euvolemic hyponatremia 4
• Treatment of the underlying cause, such as heart failure or liver disease 3, 4

Special Considerations

• Patients with chronic hyponatremia require careful management to avoid overly rapid correction and osmotic demyelination syndrome 3, 5, 6
• Patients with hyponatremic encephalopathy require urgent treatment with hypertonic saline to reverse cerebral edema 5, 6
• Patients with heart failure may benefit from treatment with vaptans to improve congestive symptoms, but the long-term effects of these medications are not well established 7