What is the treatment for euvolemic hyponatremia?

Treatment of Euvolemic Hyponatremia

Euvolemic hyponatremia should be managed based on the specific underlying cause, with fluid restriction as first-line therapy for most cases and vasopressin receptor antagonists (vaptans) for more severe or refractory cases. 1

Diagnostic Approach

Before initiating treatment, confirm euvolemic status and identify the underlying cause:

• Euvolemic hyponatremia is characterized by normal extracellular fluid volume without signs of volume depletion or overload 1
• Most common cause is Syndrome of Inappropriate Antidiuresis (SIAD) 2
• Diagnostic criteria for SIAD include:
  • Hyponatremia (serum sodium <135 mEq/L)
  • Hypoosmolality (plasma osmolality <275 mosm/kg)
  • Inappropriately high urine osmolality (>500 mosm/kg)
  • Urinary sodium concentration >20 mEq/L
  • Absence of hypothyroidism, adrenal insufficiency, and volume depletion 1

Treatment Algorithm Based on Severity

Mild Hyponatremia (126-135 mEq/L)

• Often does not require specific management beyond monitoring and water restriction 1
• Fluid restriction is the mainstay of treatment 1

Moderate Hyponatremia (120-125 mEq/L)

• Fluid restriction to 1,000 mL/day is recommended 1
• If ineffective after adequate trial, consider pharmacologic options 1

Severe Hyponatremia (<120 mEq/L)

• More severe fluid restriction together with albumin infusion is recommended 1
• Consider vasopressin receptor antagonists (vaptans) if fluid restriction fails 1
• For symptomatic severe hyponatremia (somnolence, seizures, coma), use hypertonic (3%) saline 3

Specific Treatment Options

Fluid Restriction

• First-line therapy for most cases of euvolemic hyponatremia 1
• Restrict fluid intake to <1 L/day 1
• Caution: Fluid restriction alone is often insufficient to correct sodium levels but can prevent further decreases 1

Pharmacologic Options

Vasopressin Receptor Antagonists (Vaptans)

• Effective for euvolemic hyponatremia, particularly SIAD 4
• Tolvaptan is FDA-approved for clinically significant euvolemic hyponatremia 4
• Important safety considerations:
  • Must be initiated in a hospital setting with close monitoring of serum sodium 4
  • Avoid correction of serum sodium >12 mEq/L/24 hours to prevent osmotic demyelination syndrome 4
  • Do not administer for more than 30 days to minimize risk of liver injury 4
  • Starting dose is 15 mg once daily, may increase to 30 mg after 24 hours, maximum 60 mg daily 4

Urea

• Alternative option for SIAD in the ICU setting 5
• Dosage: 0.5-1 g/kg/day, can be administered via gastric tube 5
• Advantages: simple, inexpensive, effective even with large fluid intake 5

Hypertonic Saline

• Reserved for severely symptomatic hyponatremia 3
• 3% hypertonic saline to increase serum sodium by 4-6 mEq/L within 1-2 hours 3
• Critical safety limit: Do not exceed correction of 10-12 mEq/L in 24 hours 1, 3

Monitoring and Safety Considerations

• Monitor serum sodium levels frequently during correction, especially in the first 24-48 hours 4
• Rate of correction should be 4-8 mEq/L per day, not exceeding 10-12 mEq/L in 24 hours 1
• For high-risk patients (alcoholism, malnutrition, advanced liver disease), aim for slower correction of 4-6 mEq/L per day 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, mutism, dysphagia, lethargy, quadriparesis) 1, 4
• If overcorrection occurs, consider relowering with electrolyte-free water or desmopressin 1

Special Considerations

• Avoid fluid restriction in patients who cannot sense or respond to thirst 4
• Vaptans should not be given to patients with altered mental state who cannot drink appropriately 1
• Drug interactions: Strong CYP3A inhibitors (ketoconazole, grapefruit juice, clarithromycin) increase vaptan exposure and risk of rapid sodium correction 1, 4
• Duration of treatment depends on the underlying cause; some patients may require long-term management 1