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, titrating up to 60 mg if needed) for patients with moderate to severe symptoms or when fluid restriction is ineffective. The management of hyponatremia depends on the underlying cause, with SIADH being the most common etiology 1.

Key Considerations

• Fluid restriction allows the kidneys to excrete excess water and gradually increase serum sodium.
• For severe symptomatic hyponatremia (Na <120 mEq/L with neurological symptoms), 3% hypertonic saline may be administered at 1-2 mL/kg/hr with careful monitoring to raise sodium by 4-6 mEq/L in the first 24 hours, avoiding correction rates exceeding 8 mEq/L/day to prevent osmotic demyelination syndrome 1.
• Addressing the underlying cause, such as adjusting medications, treating hypothyroidism, or managing adrenal insufficiency, is essential for long-term management.
• Regular monitoring of serum sodium, osmolality, and volume status is crucial during treatment.

Pharmacological Options

• Vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily, titrating up to 60 mg if needed) can be used for patients with moderate to severe symptoms or when fluid restriction is ineffective 1.
• Loop diuretics such as furosemide (20-40 mg daily) combined with salt tablets may be used in some cases to promote water excretion.

Important Considerations

• The treatment of hypovolaemic hyponatremia consists of administration of sodium together with identification of the causative factor (usually excessive diuretic administration) 1.
• Hypertonic sodium chloride administration to patients with decompensated cirrhosis may improve natremia but enhances volume overload and worsens the amount of ascites and oedema, and should be limited to severely symptomatic hyponatremia 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.

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.