How is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) managed?

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Fluid restriction is the first-line treatment for SIADH, with a target of 1-1.5 L/day for most patients with mild to moderate hyponatremia. 1, 2

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 concentration (>20 mEq/L) in the absence of hypothyroidism, adrenal insufficiency, or volume depletion 1
• Evaluation should include physical examination findings, basic laboratory studies, and invasive monitoring when available 2
• The critical factor in distinguishing SIADH from cerebral salt wasting is determination of extracellular fluid volume status, with SIADH characterized by euvolemia 3

Treatment Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Na <120 mmol/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, 3
• Monitor serum sodium every 2 hours initially 1
• Total correction should not exceed 8-10 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 3, 4
• For patients with malnutrition, alcoholism, or advanced liver disease, use more cautious correction rates (4-6 mmol/L per day) 3

Moderate Hyponatremia (Na 120-125 mmol/L)

• Fluid restriction to 1-1.5 L/day 1, 2
• Consider albumin infusion in hospitalized patients 2
• Monitor serum sodium levels regularly 1

Mild Hyponatremia (Na 126-135 mmol/L)

• Monitor serum electrolytes without specific intervention 2
• Continue diuretic therapy if present, but observe serum electrolytes 2
• Do not water restrict 2

Pharmacological Options

Second-Line Treatments

• Demeclocycline can be considered for chronic SIADH when fluid restriction is ineffective or poorly tolerated 2, 1, 5
• Urea, diuretics, and lithium are alternative options for SIADH management 2, 6

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan is FDA-approved for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including SIADH 4
• Initiate tolvaptan in a hospital setting with close monitoring of serum sodium 4
• Starting dose is 15 mg once daily, which can be increased to 30 mg after 24 hours, and then to 60 mg as needed 4
• Do not administer tolvaptan for more than 30 days to minimize risk of liver injury 4
• Avoid fluid restriction during the first 24 hours of tolvaptan therapy 4
• Clinical trials showed tolvaptan significantly increased serum sodium compared to placebo in patients with hyponatremia 4

Special Considerations

• In neurosurgical patients with subarachnoid hemorrhage at risk for vasospasm, fluid restriction should be avoided 3, 2
• Fludrocortisone may be considered in the treatment of hyponatremia in subarachnoid hemorrhage patients at risk of vasospasm 2
• Treatment of the underlying cause of SIADH is essential for long-term management 1, 7

Common Pitfalls to Avoid

• Overly rapid correction of hyponatremia (>12 mmol/L/24 hours) can cause osmotic demyelination syndrome 4, 1
• Inadequate monitoring during active correction of hyponatremia 1
• Using fluid restriction in cerebral salt wasting instead of SIADH 3
• Failing to recognize and treat the underlying cause 1, 3
• Discontinuing vaptans abruptly without monitoring for hyponatremic relapse 6