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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The first-line treatment for SIADH is fluid restriction (1-1.5 L/day), with vasopressin receptor antagonists (vaptans) recommended for cases with severe hyponatremia (<125 mmol/L) and neurologic symptoms. 1

Diagnosis and Classification

Before initiating treatment, confirm the diagnosis of SIADH:

• Euvolemic hyponatremia with urine sodium >20-40 mEq/L 1
• Exclude other causes of hyponatremia (hypothyroidism, adrenal insufficiency)
• Classify severity based on sodium levels:
  • Mild: 126-135 mEq/L
  • Moderate: 120-125 mEq/L
  • Severe: <120 mEq/L 1

Treatment Algorithm

For Symptomatic Severe Hyponatremia (Medical Emergency)

• Initiate in hospital setting with close monitoring of serum sodium 2
• For severe symptoms (seizures, coma):
  • Administer 3% hypertonic saline
  • Monitor sodium levels every 2 hours initially 1
  • Target correction rate: 4-6 mEq/L per 24 hours, not exceeding 8 mEq/L per 24 hours 1
  • CAUTION: Too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome 2

For Chronic/Non-Emergency SIADH

1. First-line: Fluid Restriction

   • Restrict to 1-1.5 L/day 1
   • Avoid hypotonic fluids which can worsen hyponatremia 1
   • Ensure adequate solute intake (salt and protein) 3

2. Second-line (if fluid restriction fails or is poorly tolerated):

   • Tolvaptan (Vasopressin Receptor Antagonist)

     • Starting dose: 15 mg once daily 2
     • Can be titrated to 30 mg, then 60 mg once daily as needed 2
     • Monitor serum sodium at 0,6,24, and 48 hours after initiation 4
     • Limited to ≤30 days due to risk of liver injury 2
     • Contraindicated in hypovolemic hyponatremia 2
     • Avoid fluid restriction during first 24 hours of therapy 2

   • Urea

     • Effective and safe alternative 3
     • Enhances free water excretion

Clinical Evidence for Treatment Options

Tolvaptan Efficacy

In clinical trials (SALT-1 and SALT-2), tolvaptan significantly increased serum sodium compared to placebo:

• In patients with serum sodium <125 mEq/L, tolvaptan increased sodium by 5.7 mEq/L vs 1.0 mEq/L with placebo at day 4 2
• By day 30, tolvaptan increased sodium by 10.0 mEq/L vs 4.1 mEq/L with placebo 2
• Fewer tolvaptan-treated patients required fluid restriction (14% vs 25% with placebo) 2

Important Considerations

• Monitoring: Serum sodium should be checked every 2 hours initially during acute correction, then every 4 hours during initial treatment 1

• Rate of Correction: The recommended rate for chronic hyponatremia is 4-6 mEq/L per 24-hour period, not exceeding 8 mEq/L per 24 hours 1

• Discontinuation: When discontinuing tolvaptan, monitor for hyponatremic relapse; may need to taper dose or restrict fluid intake 4

• Treatment Duration: Tolvaptan should not be administered for more than 30 days to minimize risk of liver injury 2

Special Considerations

• Elderly patients may be more susceptible to osmotic demyelination syndrome; consider slower correction rates
• Patients with malnutrition, alcoholism, or advanced liver disease require slower correction rates 2
• Untreated hyponatremia can lead to severe complications including seizures, coma, and death, with mortality rates of 25% when sodium levels fall below 120 mEq/L 1

Treatment Pitfalls to Avoid

• Avoid hypotonic fluids in patients with hyponatremia 1
• Do not use vaptans for hypovolemic hyponatremia 2
• Do not exceed recommended correction rates to prevent osmotic demyelination syndrome 1
• Do not confuse SIADH with cerebral salt wasting, which requires different management 5
• Avoid fluid restriction in cerebral salt wasting as it can be hazardous 5