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

Treatment of SIADH

For SIADH, fluid restriction to 1 L/day is the cornerstone of first-line treatment for mild to moderate asymptomatic cases, while severe symptomatic hyponatremia requires immediate 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1

Acute Severe Symptomatic SIADH (Seizures, Altered Mental Status, Coma)

This is a medical emergency requiring immediate intervention:

• Transfer to ICU for close monitoring 1
• Administer 3% hypertonic saline as 100-150 mL IV boluses over 10 minutes, repeatable up to 3 times at 10-minute intervals until symptoms improve 1, 2
• Target correction: 6 mmol/L over first 6 hours or until severe symptoms resolve 1, 2
• Critical safety limit: Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 1, 2, 3
• Monitor serum sodium every 2 hours initially 1

High-Risk Populations Requiring Slower Correction (4-6 mmol/L per day):

• Advanced liver disease 1, 2
• Alcoholism or severe malnutrition 1, 2, 3
• Baseline sodium <120 mmol/L 1

Mild to Moderate Asymptomatic or Chronic SIADH

First-Line Treatment:

• Fluid restriction to 1 L/day 1, 2, 4
• Adequate solute intake (salt and protein) 5
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response 1

Second-Line Pharmacological Options (if fluid restriction fails):

Oral sodium chloride supplementation:

• 100 mEq three times daily if no response to fluid restriction alone 1, 2

Demeclocycline:

• Induces nephrogenic diabetes insipidus, reducing kidney response to ADH 1, 6
• Long history of use in persistent SIADH cases 1

Urea:

• Considered very effective and safe in recent literature 1, 5
• Dosing: 40 g in 100-150 mL normal saline every 8 hours for 1-2 days in neurosurgical patients 1

Tolvaptan (vasopressin receptor antagonist):

• FDA-approved for clinically significant euvolemic hyponatremia 1, 3
• Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 1, 3
• Must initiate and re-initiate in hospital setting with close sodium monitoring 3
• Do not use for more than 30 days due to hepatotoxicity risk 3
• Contraindicated with strong CYP3A inhibitors 3
• Avoid fluid restriction during first 24 hours of tolvaptan therapy 3

Critical Monitoring Requirements

During active correction:

• Severe symptoms: Check sodium every 2 hours 1
• After symptom resolution: Check every 4 hours 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1, 2

If overcorrection occurs (>8 mmol/L in 24 hours):

• Immediately discontinue hypertonic fluids 1, 2
• Switch to D5W (5% dextrose in water) to relower sodium 1, 2
• Consider desmopressin administration 1, 2

Treatment of Underlying Cause

Essential component of management:

• Discontinue offending medications (SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, vincristine, cisplatin, NSAIDs, opioids) 1, 6
• Treat underlying malignancy in paraneoplastic SIADH (particularly SCLC) 1
• Address CNS disorders, pulmonary pathology, or postoperative states 1

Special Considerations

Neurosurgical patients:

• Critical distinction: SIADH vs Cerebral Salt Wasting (CSW) 1, 2
• SIADH: Euvolemic, CVP 6-10 cm H₂O, treat with fluid restriction 1
• CSW: Hypovolemic, CVP <6 cm H₂O, treat with volume/sodium replacement, NOT fluid restriction 1, 2
• In subarachnoid hemorrhage at risk for vasospasm: avoid fluid restriction, consider fludrocortisone 1, 2

Comparative efficacy of correction rates:

• Hypertonic saline: 3.0 mEq/L/day (most rapid) 1
• Tolvaptan: 3.0 mEq/L/day (equivalent) 1
• Fluid restriction: 1.0 mEq/L/day (slowest but safest for chronic management) 1

Common Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome 1, 2
• Inadequate monitoring during active correction 1, 2
• Using fluid restriction in cerebral salt wasting instead of SIADH 1, 2
• Failing to recognize and treat the underlying cause 1, 2
• Ignoring mild hyponatremia (130-135 mmol/L) which increases fall risk and mortality 2
• Using tolvaptan in patients with advanced liver disease without extreme caution due to GI bleeding risk 2