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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

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

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 inappropriately high urinary sodium concentration (> 20 mEq/L) in the absence of hypothyroidism, adrenal insufficiency, or volume depletion 1
• Assessment of volume status is critical to differentiate SIADH (euvolemic) from other causes of hyponatremia such as cerebral salt wasting (hypovolemic) 1
• A serum uric acid level < 4 mg/dL in the presence of hyponatremia has a positive predictive value for SIADH of 73-100% 1

Treatment Algorithm Based on Severity

For Severe Symptomatic Hyponatremia (seizures, coma)

• Transfer to ICU for close monitoring 1
• 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 initially 1
• Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2
• For patients with malnutrition, alcoholism, or advanced liver disease, use more cautious correction rates (4-6 mmol/L per day) 1

For Mild Symptomatic or Asymptomatic Hyponatremia

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2, 3
• Avoid fluid restriction in the first 24 hours of therapy to prevent overly rapid correction 4
• Fluid restriction alone typically results in a modest rise of 3-4 mmol/L in serum sodium 3
• If no response to fluid restriction, consider:
  • Oral sodium chloride supplementation 1
  • Urea as an effective and safe second-line treatment 5
  • Demeclocycline as a second-line treatment 1, 6
  • Vasopressin receptor antagonists (tolvaptan) for refractory cases 4

Pharmacological Options

Tolvaptan (Vasopressin Receptor Antagonist)

• Indicated for 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) 4
• Must be initiated in a hospital setting where serum sodium can be closely monitored 4
• Starting dose is 15 mg once daily, which can be increased to 30 mg after 24 hours, and then to 60 mg if needed 4
• Avoid fluid restriction during the first 24 hours of therapy 4
• Significantly increases serum sodium compared to placebo (4.0 vs 0.4 mEq/L at Day 4) 4
• Should not be used for more than 30 days to minimize risk of liver injury 4

Other Pharmacological Options

• Demeclocycline can induce a negative free-water balance 6
• Urea is considered very effective and safe for chronic SIADH 5
• Fludrocortisone has been studied primarily in neurosurgical patients 1

Monitoring and Safety Considerations

• Monitor serum sodium levels closely: every 2 hours during initial correction for severe symptoms, then every 4-6 hours 1, 2
• Do not exceed correction of 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2
• For tolvaptan, measure serum sodium after 0,6,24, and 48 hours of treatment 7
• After discontinuation of tolvaptan therapy for longer than 5-6 days, monitor for hyponatremic relapse 7

Special Considerations

• In patients with subarachnoid hemorrhage at risk for vasospasm, fluid restriction should be avoided 1
• In SCLC patients with paraneoplastic SIADH, treatment of the underlying malignancy is important alongside hyponatremia management 1
• Distinguish between SIADH and cerebral salt wasting (CSW) in neurosurgical patients, as CSW requires volume and sodium replacement rather than fluid restriction 1, 2

Common Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome 1
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting instead of SIADH 1
• Failing to recognize and treat the underlying cause 1
• Ignoring mild hyponatremia as clinically insignificant 2

Treatment Response Expectations

• Fluid restriction typically induces a modest early rise in serum sodium (3-4 mmol/L) with minimal additional rise thereafter 3
• More than one-third of patients fail to reach a serum sodium ≥130 mmol/L after 3 days of fluid restriction, indicating the need for additional therapies in some patients 3
• Hyponatremia usually improves after successful treatment of the underlying cause of SIADH 1