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

SIADH Treatment

For SIADH, fluid restriction to 1 L/day is the cornerstone of first-line treatment for mild to moderate 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, 2

Treatment Algorithm Based on Symptom Severity

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

• Transfer to ICU immediately 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 during initial correction phase 1
• Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2, 3
• After severe symptoms resolve, transition to fluid restriction 1

Mild Symptomatic or Asymptomatic SIADH (Sodium < 120 mEq/L)

• Fluid restriction to 1 L/day is the primary treatment 1, 2, 4
• If no response to fluid restriction after several days, add oral sodium chloride 100 mEq three times daily 1
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response 1
• Expect modest early rise in sodium (median 3 mmol/L after 3 days), with minimal additional rise thereafter 4

Second-Line Pharmacological Options

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan is FDA-approved for clinically significant euvolemic hyponatremia 3
• Starting dose: 15 mg once daily, can titrate to 30 mg after 24 hours, maximum 60 mg daily 3
• Must initiate and re-initiate in hospital where serum sodium can be monitored closely 3
• Monitor serum sodium at 0,6,24, and 48 hours after starting treatment to prevent overly rapid correction 5
• Do not administer for more than 30 days to minimize risk of liver injury 3
• Avoid fluid restriction during first 24 hours of vaptan therapy; patients can drink to thirst 3

Alternative Agents

• Demeclocycline can be considered as second-line treatment when fluid restriction is ineffective or poorly tolerated 1, 6
• Urea is an effective option, particularly in neurosurgical patients 1, 2
• Loop diuretics, lithium, and fludrocortisone have limited supporting data 6

Critical Correction Rate Guidelines

Standard Patients

• Maximum correction: 8 mmol/L in 24 hours 1, 2, 3
• For severe symptoms: correct 6 mmol/L over first 6 hours, then only 2 mmol/L additional in next 18 hours 1

High-Risk Patients (Advanced Liver Disease, Alcoholism, Malnutrition)

• More cautious correction: 4-6 mmol/L per day 1, 2
• These patients are at higher risk for osmotic demyelination syndrome 1, 3

Treatment of Underlying Cause

• Discontinue offending medications (carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, vincristine, cisplatin, vinca alkaloids) 1
• Treat underlying malignancy in paraneoplastic SIADH (particularly SCLC) 1
• Hyponatremia usually improves after successful treatment of underlying cause 1

Monitoring Requirements

• During active correction: Check sodium every 2 hours for severe symptoms, every 4 hours for mild symptoms 1
• After stabilization: Daily monitoring until target reached 1
• Watch for osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically 2-7 days after rapid correction 1, 3

Common Pitfalls to Avoid

• Never use fluid restriction in cerebral salt wasting (CSW) instead of SIADH—this worsens outcomes 1, 2, 7
• Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours—this causes osmotic demyelination 1, 3
• Never use tolvaptan with strong CYP3A inhibitors (contraindicated) 3
• Never use tolvaptan in hypovolemic hyponatremia (contraindicated) 3
• Inadequate monitoring during active correction leads to complications 1
• Failing to identify and treat underlying cause perpetuates the problem 1

Special Considerations

• In subarachnoid hemorrhage patients at risk for vasospasm: avoid fluid restriction; consider fludrocortisone 1, 2
• Efficacy of fluid restriction: Only 61% of patients reach sodium ≥130 mmol/L after 3 days, emphasizing need for additional therapies in some patients 4
• After discontinuing vaptan therapy: Resume fluid restriction and monitor for hyponatremic relapse 5