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

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The management of SIADH should focus on fluid restriction as first-line treatment for mild cases, while using 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 2, 1
• Laboratory evaluation should include serum and urine osmolality, urine electrolytes, and assessment of extracellular fluid volume status to differentiate SIADH from other causes of hyponatremia 1, 3

Treatment Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Serum Na < 120 mEq/L with neurological symptoms)

• 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
• 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, 3
• For patients with advanced liver disease, alcoholism, or malnutrition, use more cautious correction rates (4-6 mmol/L per day) 1, 3

Mild to Moderate Hyponatremia or Asymptomatic Patients

• Fluid restriction to 1 L/day is the cornerstone of treatment 2, 1
• If no response to fluid restriction, consider adding oral sodium chloride 100 mEq three times daily 1
• Consider pharmacological options for resistant cases:
  • Demeclocycline as a second-line treatment 1
  • Vasopressin receptor antagonists (tolvaptan) for refractory cases 1, 4
  • Urea is considered an effective and safe treatment option 5, 6

Pharmacological Treatment Options

• Tolvaptan (vasopressin V2 receptor antagonist):

  • Initial dose: 15 mg once daily 4
  • Can be increased to 30 mg once daily after 24 hours, and up to 60 mg once daily as needed 4
  • Must be initiated in a hospital setting where serum sodium can be closely monitored 4
  • Significantly increases serum sodium levels compared to placebo 4
  • Should not be used for more than 30 days to minimize risk of liver injury 4
  • Reduces the need for fluid restriction (14% vs 25% with placebo) 4

• Urea:

  • Effective for chronic hyponatremia secondary to SIADH 5, 6
  • Well-tolerated even in long-term use 6
  • May allow decrease in fluid restriction 6

Special Considerations

• In patients with subarachnoid hemorrhage at risk for vasospasm, fluid restriction should be avoided 1
• Fludrocortisone may be considered in neurosurgical patients 1
• Treatment of underlying cause (e.g., small cell lung cancer) is important alongside hyponatremia management 2, 1
• Discontinue hypotonic fluids, such as D5 water, as they worsen hyponatremia 1

Common Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome 1, 4
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting instead of SIADH 1, 3
• Failing to recognize and treat the underlying cause 1
• Misdiagnosing volume status (SIADH is euvolemic) 1, 3

Monitoring

• For severe cases: monitor serum sodium every 2 hours during initial correction 1
• For mild cases: monitor daily to ensure correction does not exceed 8 mmol/L in 24 hours 1
• If overcorrection occurs, consider relowering with electrolyte-free water or desmopressin 3
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 3

By following this algorithm and carefully monitoring serum sodium levels, SIADH can be effectively managed while minimizing the risk of complications such as osmotic demyelination syndrome.