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

From the Guidelines

Management of hyponatremia should prioritize identifying the underlying cause and correcting sodium levels at an appropriate rate to avoid complications, with the goal of improving morbidity, mortality, and quality of life. The approach to managing hyponatremia depends on the etiology, chronicity, severity, and urgency of the condition. For patients with cirrhosis and ascites, the management of hyponatremia is guided by the American Association for the Study of Liver Diseases practice guidance 1.

Key Considerations

• For acute hyponatremia (onset within 48 hours), rapid correction is recommended to prevent cerebral edema without a concern for osmotic demyelination syndrome (ODS) 1.
• For chronic hyponatremia, more gradual and measured correction is necessary to avoid overcorrection and mitigate the risk of ODS 1.
• Hypovolemic hyponatremia should be treated with fluid resuscitation, typically with 5% IV albumin or crystalloid (preferentially lactated Ringer’s) solution, and discontinuation of diuretics and/or laxatives 1.
• Euvolemic hyponatremia should be managed based on the specific underlying cause, and for hypervolemic hyponatremia, treatment includes fluid restriction, reduction or discontinuation of diuretics and laxatives, administration of hyperoncotic albumin, and/or vasopressin receptor antagonists (“vaptans”) 1.

Treatment Approaches

• For severe symptomatic hyponatremia (sodium <120 mEq/L) with seizures or altered mental status, 3% hypertonic saline should be administered at 100-150 mL over 10-20 minutes, which can be repeated if symptoms persist.
• The correction rate should not exceed 8-10 mEq/L in the first 24 hours and 18 mEq/L in 48 hours to prevent osmotic demyelination syndrome.
• For SIADH, fluid restriction combined with oral salt tablets (1-2 g three times daily) may be effective, and vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) can be used for resistant cases but require careful monitoring 1.
• Regular monitoring of serum sodium (every 2-4 hours initially in severe cases) is essential to ensure appropriate correction rates and prevent neurological complications.

Underlying Causes

• Underlying causes must be addressed simultaneously, including discontinuing offending medications, treating infections, or managing endocrine disorders.
• The management of hyponatremia should be individualized based on the patient's clinical presentation, underlying cause, and response to treatment.

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.

Management of Hyponatremia: Tolvaptan is effective in increasing serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.

• The dose of tolvaptan can 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) is reached.
• Fluid restriction was to be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
• Tolvaptan caused a statistically greater increase in serum sodium during both periods in both studies, and this effect was also seen across all disease etiology subsets (e.g., CHF, cirrhosis, SIADH/other) 2.

From the Research

Management of Hyponatremia

• Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 3.
• Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma) 3, 4.
• The approach to managing hyponatremia should consist of treating the underlying cause, and patients should be categorized according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3, 4, 5.

Treatment of Hyponatremia

• Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 3.
• Hypertonic saline is reserved for patients with severely symptomatic hyponatremia, and the goal is to increase 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 within the first 24 hours 3, 4, 6.
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition 3, 6, 7.

Classification and Diagnosis of Hyponatremia

• Hyponatremia is classified based on volume status (hypovolemia, euvolemia, and hypervolemia) 4, 5.
• Diagnosis is based on findings from the history, physical examination, laboratory studies, and evaluation of volume status 4, 5.
• Treatment is based on symptoms and underlying causes, and may involve fluid restriction, isotonic saline, diuresis, or a combination of these therapies 4, 5.