What is the approach to managing chronic hyponatremia (low sodium levels in the blood)?

From the Guidelines

The approach to chronic hyponatremia in patients with cirrhosis involves water restriction and cessation of diuretics for moderate hyponatremia, with a goal to increase serum sodium by 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, as recommended by the American Association for the Study of Liver Diseases 1.

Key Considerations

• For mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms, no specific management is required apart from monitoring and water restriction 1.
• Water restriction to 1,000 mL/day and cessation of diuretics is recommended for moderate hyponatremia (120-125 mEq/L) 1.
• Vasopressin receptor antagonists, such as tolvaptan, can be used with caution for a short term (≤30 days) to raise serum sodium in patients with cirrhosis, but their use should be carefully monitored due to potential side effects and interactions with other medications 1.

Treatment Strategies

• For hypervolemic hyponatremia seen in cirrhosis, fluid restriction combined with albumin infusion may be recommended for severe hyponatremia (<120 mEq/L) 1.
• Hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia, or those with imminent liver transplantation 1.
• Regular monitoring of serum sodium, typically every 4-6 hours during active correction, is essential to ensure safe correction rates and prevent complications such as osmotic demyelination syndrome 1.

Important Considerations

• The use of vaptans, such as tolvaptan, should be started in the hospital with close clinical monitoring and assessment of serum sodium levels to avoid rapid increases in serum sodium concentration 1.
• Patients with cirrhosis and hyponatremia should be managed with a multidisciplinary approach to mitigate the risk of osmotic demyelination syndrome and other complications 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 approach to chronic hyponatremia involves the use of tolvaptan, which has been shown to be effective in increasing serum sodium levels in patients with euvolemic or hypervolemic hyponatremia. Key points to consider include:

• Tolvaptan dosage: The initial dose is 15 mg once daily, which can be increased to 30 mg once daily, and then to 60 mg once daily, as needed, to achieve normonatremia.
• Fluid restriction: Fluid restriction should be avoided during the first 24 hours of therapy to prevent overly rapid correction of serum sodium.
• Monitoring: Serum sodium concentrations should be monitored regularly, including at 8 hours after study drug initiation and daily up to 72 hours.
• Efficacy: Tolvaptan has been shown to be effective in increasing serum sodium levels in patients with chronic hyponatremia, with a statistically significant increase in serum sodium compared to placebo 2.

From the Research

Approach to Chronic Hyponatremia

• The conventional treatment for chronic hyponatremia consists of fluid restriction in the presence of euvolemia or hypervolemia, while loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis, and nephrotic syndrome 3.
• In cases of hypovolemic conditions, intravenous isotonic or hypertonic solutions are administered 3.
• The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance 3.
• A new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans, with tolvaptan being the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults 3, 4.
• Tolvaptan has been used successfully in children with chronic hyponatremia due to SIADH, although few data are available in pediatric patients 3.
• Overly rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome, and European guidelines recommend a correction to ≤10 mEq/L in 24 hours to prevent this complication 5.
• However, osmotic demyelination syndrome may occur despite adherence to these guidelines, and specific risk factors for this complication include alcohol use disorder, hypokalemia, liver disease, and malnutrition 5.
• In patients with severe hyponatremia and high-risk features, especially those with serum sodium <115 mEq/L, it is recommended to limit serum sodium correction to <8 mEq/L 5.
• Thiamine supplementation is advisable for any patient with hyponatremia whose dietary intake has been poor 5.
• Vaptans are well suited to the treatment of chronic hyponatremia associated with SIADH and hypervolemic states like cirrhosis or congestive heart failure, but no data are available on the use of vaptans in acute hyponatremia, and they are not indicated in hypovolemic hyponatremia 6.
• Determination of the etiology of chronic hyponatremia requires analysis of serum osmolality, volume status, and urine osmolality and sodium level, and correct diagnosis points to the appropriate treatment and helps identify risk factors for accelerated correction of the serum sodium level 7.