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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Fluid restriction (<1-1.5 L/day) is the first-line treatment for SIADH, with tolvaptan as an effective second-line therapy for patients who don't respond to fluid restriction. 1

Diagnosis and Classification

Before initiating treatment, confirm SIADH diagnosis based on:

• Hyponatremia (serum sodium <134 mEq/L)
• Hypoosmolality (plasma osmolality <275 mosm/kg)
• Inappropriately high urine osmolality (>500 mosm/kg)
• Inappropriately high urinary sodium (>20 mEq/L)
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Categorize patients by volume status:

• Euvolemic: No signs of dehydration or fluid overload (typical of SIADH)
• Hypovolemic: Dehydration, orthostatic hypotension
• Hypervolemic: Edema, ascites, fluid overload 1

Treatment Algorithm

First-Line Treatment

1. Fluid restriction (FR):
   • Restrict to <1-1.5 L/day 1
   • Consider salt supplementation (3g/day) if needed 1
   • FR induces a modest early rise in plasma sodium but may have limited efficacy; only 61% of patients reach sodium ≥130 mmol/L after 3 days 2

Second-Line Treatment (if inadequate response to fluid restriction)

1. Tolvaptan (vasopressin V2 receptor antagonist):

   • Starting dose: 15 mg once daily
   • Can titrate to 30 mg, then 60 mg daily as needed 1, 3
   • IMPORTANT: Must be initiated in a hospital setting with close sodium monitoring 1, 3
   • Limited to 30 days due to risk of liver injury 1, 3
   • Contraindicated in:
     • ADPKD patients
     • Patients unable to sense/respond to thirst
     • Hypovolemic hyponatremia
     • Patients taking strong CYP3A inhibitors
     • Anuria
     • Hypersensitivity to tolvaptan 3

2. Urea:

   • Considered effective and safe for SIADH 4
   • Alternative when tolvaptan is contraindicated or unavailable

For Severe Symptomatic Cases

1. Hypertonic saline (3%):
   • For patients with severe symptoms (somnolence, seizures, coma)
   • Administer as 100-150 mL IV bolus or continuous infusion 4
   • Target correction: 4-6 mEq/L within 1-2 hours 5
   • Transfer to ICU with close monitoring (sodium levels every 2 hours) 1

Monitoring and Safety Considerations

Sodium Correction Rates

• Acute hyponatremia (<48 hours): Correct at 1 mEq/L/hour 1
• Chronic hyponatremia: Correct at <0.5 mEq/L/hour 1
• NEVER exceed 8 mEq/L in 24 hours or 6 mEq/L in 6 hours 1
• Avoid rapid correction (>12 mEq/L/24 hours) to prevent osmotic demyelination syndrome 1, 3

Monitoring Protocol

• Check serum electrolytes every 4-6 hours initially 1
• For symptomatic patients, check sodium every 2-4 hours initially 1
• Once stable, monitor daily until normal, then weekly for 1 month 1
• Monitor weight daily to assess fluid status 1

Special Considerations

• Avoid fluid restriction during first 24 hours of tolvaptan therapy 3
• Strong CYP3A inhibitors (ketoconazole, grapefruit juice, clarithromycin) can increase tolvaptan levels and risk of rapid sodium correction 1
• Loop diuretics may be used in combination with salt supplementation in selected cases 1
• Demeclocycline has limited current use due to side effects 1, 6
• Dietary sodium restriction (2-3g/day) is recommended for long-term management 1

Patient Education

• Educate patients about symptoms of electrolyte imbalance to report (weakness, confusion, muscle cramps) 1
• For patients on tolvaptan, advise they can continue fluid intake in response to thirst 3
• After discontinuing tolvaptan, patients should resume fluid restriction and be monitored for changes in sodium levels 3

Remember that even mild hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures, making appropriate treatment essential for reducing morbidity and mortality 5.