How do I treat persistent hyponatremia (low sodium levels) with euvolemic (normal fluid volume) hypo-osmolar (low osmolarity) state?

From the Guidelines

Treatment of persistent euvolemic hypo-osmolar hyponatremia should involve fluid restriction to 800-1000 mL/day as the first-line treatment, with pharmacological options such as vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) considered for patients with moderate to severe symptoms or when fluid restriction is ineffective. The goal of treatment is to gradually increase serum sodium levels without exceeding 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1.

Key Considerations

• Fluid restriction allows the kidneys to excrete excess water and gradually increase serum sodium.
• Vasopressin receptor antagonists like tolvaptan work by blocking ADH receptors in the kidneys, promoting water excretion without electrolyte loss.
• Addressing the underlying cause is essential, which may include discontinuing medications that contribute to SIADH, treating hypothyroidism, or addressing adrenal insufficiency.
• Regular monitoring of serum sodium, fluid status, and neurological symptoms is crucial during treatment.

Pharmacological Options

• Oral urea (15-30 g daily) can increase solute excretion and free water clearance.
• Salt tablets (1-2 g three times daily) and loop diuretics like furosemide (20-40 mg daily) may be used as adjunctive therapy.

Important Safety Considerations

• Correction of sodium should be gradual to prevent osmotic demyelination syndrome.
• Vaptans should not be given to patients in an altered mental state who cannot drink appropriate amounts of fluid due to the risk of dehydration and hypernatremia 1.
• Treatment with vaptans should always be started in the hospital with close clinical monitoring and assessment of serum sodium levels.

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.

Treatment of Persistent Hyponatremia Euvolemic Hypo-osmolar:

• 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 in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in serious neurologic sequelae.
• Avoid fluid restriction during the first 24 hours of therapy to avoid overly rapid correction of serum sodium 2.

From the Research

Treatment of Persistent Hyponatremia Euvolemic Hypo-osmolar

• The treatment of euvolemic hyponatremia depends on the underlying cause, severity of symptoms, and rate of onset 3, 4, 5, 6, 7.
• For patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH), treatment options include fluid restriction, hypertonic saline, urea, and vaptans 3, 4, 5, 7.
• Vaptans, such as vasopressin receptor antagonists, can be effective in treating euvolemic hyponatremia, but may cause side effects such as thirst, polydipsia, and frequency of urination 4, 5.
• In patients with severe symptoms, such as somnolence, obtundation, coma, seizures, or cardiorespiratory distress, bolus hypertonic saline may be used to rapidly correct the serum sodium level 3, 7.
• However, overly rapid correction of chronic hyponatremia can cause osmotic demyelination, a rare but severe neurological condition, and the correction limit should not exceed 8-10 mEq/L within the first 24 hours 3, 4, 7.
• Free water restriction combined with increased solute intake, such as urea, is also an effective therapy for patients with SIADH 7.
• It is essential to monitor serum sodium levels closely during treatment and adjust the therapy as needed to prevent overly rapid correction or relapse of hyponatremia 4, 7.