What is the recommended treatment for correcting hyponatremia (low sodium levels) in patients with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Treatment of Hyponatremia in SIADH

Fluid restriction to 1 L/day is the first-line treatment for asymptomatic or mild SIADH-induced hyponatremia, while hypertonic 3% saline is reserved for severe symptomatic cases with careful monitoring to prevent osmotic demyelination syndrome. 1, 2

Diagnosis of SIADH

SIADH is characterized by:

• Hyponatremia (serum sodium < 134 mEq/L) 1
• Hypoosmolality (plasma osmolality < 275 mosm/kg) 1
• Inappropriately high urine osmolality (> 500 mosm/kg) 1
• Inappropriately high urinary sodium concentration (> 20 mEq/L) 1
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Treatment Algorithm Based on Symptom Severity

Severe Symptomatic Hyponatremia (Mental status changes, seizures, coma)

• Administer 3% hypertonic saline with a goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1, 2
• Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2, 3
• Monitor serum sodium every 2 hours initially 1
• Transfer to ICU for close monitoring 1
• Calculate sodium deficit using formula: Desired increase in Na (mEq/L) × (0.5 × ideal body weight in kg) 2
• When severe symptoms resolve, transition to mild/asymptomatic protocol 1

Mild Symptomatic Hyponatremia (Nausea, vomiting, headache) or Na < 120 mEq/L

• Fluid restriction to 1 L/day 1, 2
• Monitor sodium every 4 hours 1
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1, 2
• Consider high protein diet to increase solute intake 2

Asymptomatic Hyponatremia

• Fluid restriction to 1 L/day 1, 2
• Monitor sodium daily 1
• If no response after 24-48 hours, consider adding oral sodium chloride 100 mEq three times daily 2

Second-Line Treatment Options

If fluid restriction and salt supplementation fail to correct hyponatremia:

• Vasopressin receptor antagonists (vaptans):

  • Tolvaptan starting at 15 mg once daily, can be increased to 30 mg after 24 hours, maximum 60 mg daily 4
  • Must be initiated in hospital setting with close monitoring of serum sodium 4
  • Avoid fluid restriction during first 24 hours of therapy 4
  • Do not administer for more than 30 days due to risk of liver injury 4

• Demeclocycline: Alternative option mentioned in guidelines 1

• Urea: Considered effective and safe as second-line therapy 5

Monitoring and Safety Considerations

• For severe hyponatremia correction, limit rate to < 8 mmol/L per 24 hours 1, 2, 3
• For chronic hyponatremia, slower correction is safer to prevent osmotic demyelination syndrome 3
• Patients with malnutrition, alcoholism, or advanced liver disease require more cautious correction rates (4-6 mmol/L per day) 3
• Monitor for signs of overcorrection; be prepared to administer hypotonic fluids if correction occurs too rapidly 5

Common Pitfalls to Avoid

• Overly rapid correction of chronic hyponatremia leading to osmotic demyelination syndrome 3, 6
• Inadequate monitoring during active correction 3
• Using hypertonic saline in non-severe cases 7
• Failing to recognize and treat the underlying cause of SIADH 3
• Using fluid restriction in cerebral salt wasting (which can be confused with SIADH) 3

Special Considerations

• When using tolvaptan, monitor serum sodium at 0,6,24, and 48 hours to prevent overly rapid correction 8
• If tolvaptan is discontinued after more than 5-6 days, monitor for hyponatremic relapse 8
• In clinical trials, tolvaptan was more effective than placebo in increasing serum sodium levels in patients with SIADH 4
• Patients receiving tolvaptan should be advised to continue fluid intake in response to thirst 4