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

Treatment of SIADH

For mild to moderate SIADH, fluid restriction to 1 L/day is the cornerstone of first-line treatment, with demeclocycline or urea as second-line options when fluid restriction fails or is poorly tolerated. 1

Acute Severe Symptomatic SIADH

For patients with severe symptoms (seizures, altered mental status, coma), immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve. 1

• Transfer to ICU for close monitoring with serum sodium checks every 2 hours initially 1
• Never exceed 8 mmol/L total correction in 24 hours to prevent osmotic demyelination syndrome 1, 2
• For high-risk patients (advanced liver disease, alcoholism, malnutrition), limit correction to 4-6 mmol/L per day 1, 2
• Avoid fluid restriction during the first 24 hours of hypertonic saline therapy to prevent overly rapid correction 3

Chronic Mild-Moderate SIADH

First-Line: Fluid Restriction

• Restrict fluids to 1 L/day (1000 mL/day) for asymptomatic or mildly symptomatic patients 1, 2
• This achieves correction at approximately 1.0 mEq/L/day, the slowest but safest rate for chronic management 1
• If no response after adequate trial, add oral sodium chloride 100 mEq three times daily 1

Second-Line Pharmacological Options

When fluid restriction fails or is poorly tolerated, demeclocycline is recommended as second-line treatment. 1

• Demeclocycline induces nephrogenic diabetes insipidus, reducing the kidney's response to ADH 1
• Alternative second-line agents include urea (considered very effective and safe in recent literature), lithium, and loop diuretics 1, 4
• Urea is emerging as a highly effective option, though less commonly used in some regions 1, 4

Third-Line: Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan is FDA-approved for clinically significant euvolemic hyponatremia, starting at 15 mg once daily, titrated to 30 mg after 24 hours, with a maximum of 60 mg daily. 1, 3

• Tolvaptan increases serum sodium significantly more than placebo (3.0 mEq/L/day correction rate) 1
• In clinical trials, tolvaptan achieved mean increases of 4.0 mEq/L by Day 4 and 6.2 mEq/L by Day 30 versus 0.4 and 1.8 mEq/L with placebo 3
• Use with extreme caution in cirrhosis due to higher risk of gastrointestinal bleeding (10% vs 2% placebo) 2
• Monitor closely during first 24 hours to prevent overly rapid correction 1, 5

Treatment of Underlying Cause

Always identify and treat the underlying cause of SIADH, as effective treatment of the primary condition often resolves the paraneoplastic syndrome. 1

• Common causes include malignancy (especially small cell lung cancer), CNS disorders, pulmonary diseases, and medications 1, 6
• Discontinue offending medications such as carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, vincristine, and cisplatin 1, 6

Critical Monitoring Requirements

• Check serum sodium every 2 hours during acute correction of severe symptoms 1
• After symptom resolution, check every 4 hours, then daily once stable 1
• Calculate sodium deficit: Desired increase (mEq/L) × (0.5 × ideal body weight in kg) 2
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 2

Special Populations

Neurosurgical Patients

In neurosurgical patients, distinguishing SIADH from cerebral salt wasting (CSW) is critical, as CSW requires volume and sodium replacement, NOT fluid restriction. 1, 2

• CSW is characterized by hypovolemia with CVP <6 cm H₂O, while SIADH shows euvolemia with CVP 6-10 cm H₂O 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm 1, 2
• Consider fludrocortisone for hyponatremia in subarachnoid hemorrhage patients 1, 2

Cirrhotic Patients

• Require more cautious correction rates (4-6 mmol/L per day) due to higher risk of osmotic demyelination 1, 2
• Consider albumin infusion alongside fluid restriction 2
• Avoid hypertonic saline unless life-threatening symptoms present, as it worsens ascites and edema 2

Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours leads to osmotic demyelination syndrome 1, 2
• 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 (130-135 mmol/L), which increases fall risk and mortality 2

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours, immediately discontinue current fluids and switch to D5W (5% dextrose in water). 2

• Consider administering desmopressin to slow or reverse the rapid rise 2
• This is particularly critical in high-risk patients with cirrhosis, alcoholism, or malnutrition 2