What is the treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

Treatment of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The cornerstone treatment for SIADH is fluid restriction to 1 L/day for mild to moderate cases, while severe symptomatic cases require 3% hypertonic saline with careful monitoring to prevent osmotic demyelination syndrome. 1, 2

Initial Assessment and Diagnosis

• SIADH is characterized by hyponatremia (serum sodium < 134 mEq/L), hypoosmolality (plasma osmolality < 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and high urinary sodium (> 20 mEq/L) in a euvolemic patient without hypothyroidism or adrenal insufficiency 2
• Assessment of volume status is critical to differentiate SIADH (euvolemic) from cerebral salt wasting (hypovolemic) or hypervolemic hyponatremia, as treatment approaches differ significantly 1, 2
• Serum uric acid < 4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100% 2

Treatment Algorithm Based on Symptom Severity

Severe Symptomatic Hyponatremia (Seizures, Coma)

• Transfer to ICU for close monitoring 2
• Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1, 2
• Monitor serum sodium every 2 hours during initial correction 1
• Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2

Mild to Moderate Symptomatic or Asymptomatic Hyponatremia

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• Consider pharmacological options for resistant cases 2:
  • Demeclocycline (second-line treatment) 2, 3
  • Urea 4
  • Vasopressin receptor antagonists (tolvaptan) 5, 6

Special Considerations

Correction Rate Guidelines

• Do not exceed correction of 8 mmol/L in 24 hours for most patients 1, 2
• For patients with advanced liver disease, alcoholism, or malnutrition, use more cautious correction rates (4-6 mmol/L per day) 1, 2
• If overcorrection occurs, consider relowering with electrolyte-free water or desmopressin 1, 4

Pharmacological Options for Resistant Cases

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan is FDA-approved for euvolemic or hypervolemic hyponatremia 5
• Initial dose: 15 mg once daily, may increase to 30 mg after 24 hours, maximum 60 mg daily 5
• Must be initiated in hospital setting with close monitoring of serum sodium 5
• Avoid fluid restriction during first 24 hours of therapy 5
• Do not administer for more than 30 days to minimize risk of liver injury 5
• Contraindicated in hypovolemic hyponatremia and in patients taking strong CYP3A inhibitors 5

Other Pharmacological Options

• Demeclocycline: Effective for chronic SIADH when fluid restriction is ineffective 3, 6
• Urea: Considered effective and safe, especially in European practice 7, 4
• Loop diuretics and lithium: Limited data to support their use 3

Neurosurgical Patients

• Distinguish between SIADH and cerebral salt wasting (CSW) as treatment approaches differ significantly 1, 2
• In patients with subarachnoid hemorrhage at risk for vasospasm, avoid fluid restriction 1, 2
• Consider fludrocortisone for hyponatremia in subarachnoid hemorrhage patients 1

Treatment of Underlying Cause

• Identify and treat the underlying cause of SIADH when possible 1, 2
• Common causes include:
  • Malignancies (especially small cell lung cancer) 2
  • CNS disorders 1, 2
  • Medications (antidepressants, antiepileptics, chemotherapeutic agents) 2
• Effective treatment of underlying malignancy can resolve paraneoplastic SIADH 2

Common Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome 1, 2
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting instead of SIADH 1, 2
• Failing to recognize and treat the underlying cause 1, 2
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1

Long-term Management

• For chronic SIADH, continue fluid restriction as first-line therapy 6, 7
• If fluid restriction is ineffective or poorly tolerated, consider pharmacological options 6, 7
• When discontinuing any vaptan therapy, monitor for hyponatremic relapse 6
• Regular monitoring of serum sodium levels is essential during treatment 1, 4