What is the management of euvolemic hyponatremia (low sodium levels in the blood with normal fluid volume)?

From the Guidelines

Management of euvolemic hyponatremia should prioritize correcting the underlying cause while carefully correcting sodium levels, with fluid restriction being the cornerstone for most cases, as recommended by expert opinion 1. The primary treatment approach depends on symptom severity. For asymptomatic mild cases, free water restriction (< 1 L/d) is a first-line treatment.

• In cases of SIADH-related hyponatremia, additional treatments such as demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) may be used to correct hyponatremia 1.
• For life-threatening or acute symptomatic and severe (< 120 mEq/L) hyponatremia, hypertonic 3% saline IV is recommended 1. It is essential to monitor serum sodium levels frequently, especially in severe cases, to guide therapy and prevent overcorrection, which can lead to osmotic demyelination syndrome.
• Addressing underlying causes such as hypothyroidism, adrenal insufficiency, or medication effects is crucial for long-term management 1. Chronic management may require ongoing fluid restriction, salt supplementation, or maintenance doses of vasopressin 2 receptor antagonists in select cases.
• The goal is to correct sodium levels while minimizing the risk of complications, with a target sodium increase of 4-6 mEq/L in the first 6 hours for severe cases, and not exceeding 8-10 mEq/L in 24 hours or 18 mEq/L in 48 hours 1.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. 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.

Management of Euvolemic Hyponatremia:

• Tolvaptan is indicated for the treatment of clinically significant euvolemic hyponatremia.
• The recommended starting dose is 15 mg once daily, which can be increased to 30 mg once daily after at least 24 hours, and to a maximum of 60 mg once daily as needed.
• Patients should be initiated and re-initiated in a hospital where serum sodium can be monitored closely to avoid too rapid correction of hyponatremia.
• The treatment should be maintained for 30 days to minimize the risk of liver injury 2, 2.
• Key considerations:
  • Monitor serum sodium levels closely.
  • Avoid fluid restriction during the first 24 hours of therapy.
  • Patients receiving tolvaptan should be advised to continue ingestion of fluid in response to thirst.
  • Following discontinuation, patients should resume fluid restriction and be monitored for changes in serum sodium and volume status.

From the Research

Management of Euvolemic Hyponatremia

Euvolemic hyponatremia is a condition where the body has a low sodium level and a normal fluid volume. The management of this condition depends on the underlying cause, severity of symptoms, and rate of onset.

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hyponatremia 3, 4, 5, 6.
• Patients with SIADH should be treated to cure symptoms, and the treatment approach depends on the severity of symptoms 4.
• For patients with mild to moderate symptoms, fluid restriction and hypertonic saline are commonly used treatments 4.
• Vaptans, which are vasopressin receptor antagonists, have been introduced as a specific and direct therapy for SIADH and appear to be advantageous for patients and physicians 4, 5.
• However, vaptans can cause side effects such as thirst, polydipsia, and frequency of urination 4.
• In any therapy of chronic SIADH, it is essential to limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 4, 6.

Treatment Options

The treatment options for euvolemic hyponatremia include:

• Fluid restriction: This is the most effective therapy to treat patients with SIADH 6.
• Hypertonic saline: This should be used in patients with significant neurologic symptoms, and the maximal correction of serum Na level should be limited to <8 mEq over 24 hours to prevent osmotic demyelination syndrome (ODS) 3, 6.
• Vaptans: These can be used to treat patients with SIADH, but the serum sodium level should be monitored closely to prevent overly rapid correction 4, 5.
• Urea: This can be used to increase solute intake and treat patients with SIADH 6.
• Desmopressin: This can be used to prevent overly rapid Na correction in high-risk patients 6.

Important Considerations

• The distinction between acute and chronic hyponatremia is crucial in initiating proper therapy 6.
• Osmotic demyelination syndrome (ODS) can occur when rapidly correcting any chronic hyponatremia, and the maximal correction of serum Na level should be limited to <8 mEq over 24 hours to prevent ODS 3, 6.
• 0.9% saline should be avoided in the treatment of SIADH due to rapid fluctuations in serum Na levels 6.