How is SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion) managed?

Management of SIADH

The first-line treatment for SIADH is fluid restriction to 1-1.5 L/day, while vaptans (particularly tolvaptan) are the most effective second-line therapy for patients who fail to respond to fluid restriction or have severe hyponatremia. 1, 2

Understanding SIADH

SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion) is characterized by:

• Excessive release of ADH (vasopressin) leading to water retention
• Increased urinary sodium excretion
• Resulting hyponatremia despite normal or expanded extracellular fluid volume

Diagnostic Approach

To confirm SIADH diagnosis, look for:

• Hyponatremia (serum sodium <135 mmol/L)
• Euvolemic status on physical examination
• High urine osmolality with low plasma osmolality
• Elevated urine sodium (typically >30 mmol/L)
• Normal renal, adrenal, and thyroid function
• No recent diuretic use 2

Central venous pressure (CVP) measurements can help differentiate SIADH (CVP 6-10 cm H₂O) from cerebral salt wasting (CVP <6 cm H₂O) 2.

Treatment Algorithm

First-Line Treatment:

1. Fluid restriction (1-1.5 L/day) 1, 2
   • Modest effectiveness: In a randomized controlled trial, fluid restriction led to a median increase in serum sodium of 3 mmol/L after 3 days and 4 mmol/L after 30 days 3
   • Only 61% of patients achieve serum sodium ≥130 mmol/L after 3 days of fluid restriction 3
   • Helps prevent further decrease in serum sodium but rarely normalizes it completely 2

Second-Line Treatments:

1. Vaptans (V2-receptor antagonists) 2, 4

   • Tolvaptan is FDA-approved for treatment of euvolemic or hypervolemic hyponatremia, including SIADH 4
   • Start at 15 mg once daily, can be titrated to 30 mg and then 60 mg daily as needed 4
   • Significantly more effective than placebo: increases serum sodium by 4.0 mmol/L vs 0.4 mmol/L at day 4 4
   • Must be initiated in hospital setting with close monitoring of serum sodium 4

2. Urea 5

   • Considered effective and safe alternative
   • Induces osmotic diuresis
   • Poor palatability is a limitation

3. Hypertonic (3%) saline 2, 1

   • Reserved for severe symptomatic hyponatremia
   • Partially effective but short-lived effect
   • May increase ascites and edema in hypervolemic patients

Treatment Selection Based on Severity:

Mild to Moderate Hyponatremia (125-134 mmol/L), Asymptomatic:

• Fluid restriction (1-1.5 L/day)
• Ensure adequate salt intake
• Monitor serum sodium every 24-48 hours

Severe Hyponatremia (<125 mmol/L) or Symptomatic:

• Consider tolvaptan starting at 15 mg daily
• Monitor serum sodium at 6,24, and 48 hours
• Avoid fluid restriction during first 24 hours of tolvaptan therapy 4

Life-Threatening Symptoms (seizures, coma):

• 3% hypertonic saline bolus (100-150 mL)
• Target initial correction of 4-6 mmol/L within 1-2 hours 6

Critical Safety Considerations

1. Avoid overcorrection: Do not increase serum sodium by more than 8-10 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2

2. Close monitoring: Check serum sodium every 2-4 hours in severe cases, every 6-12 hours in moderate cases 1

3. Tolvaptan precautions:

   • Must be initiated in hospital setting
   • Avoid in patients unable to sense thirst
   • Contraindicated with strong CYP3A inhibitors
   • Limited to 30 days of therapy due to potential liver injury risk 4

4. Discontinuation protocol: When stopping vaptans, taper dose or reinstitute fluid restriction to prevent hyponatremic relapse 7

Common Pitfalls to Avoid

• Continuing diuretics in patients with severe hyponatremia
• Fluid restriction in patients at risk of vasospasm (particularly with subarachnoid hemorrhage)
• Rapid correction of chronic hyponatremia (>8 mmol/L/24h)
• Failing to identify and treat underlying causes of SIADH
• Inadequate monitoring during treatment, especially with vaptans 1

By following this structured approach to SIADH management, focusing on appropriate fluid restriction as first-line therapy and using vaptans as effective second-line treatment, clinicians can effectively manage this common electrolyte disorder while minimizing risks of complications.