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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The first-line treatment for SIADH is fluid restriction (<1 L/day) for mild to moderate cases, while hypertonic 3% saline IV should be used for severe or symptomatic hyponatremia (serum sodium <120 mEq/L). 1

Diagnosis Confirmation

Before initiating treatment, confirm SIADH diagnosis with the following criteria:

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

Treatment Algorithm Based on Severity

Mild to Moderate SIADH (Serum sodium 125-134 mEq/L)

1. Free water restriction (<1 L/day) 1

   • First-line treatment for asymptomatic cases
   • Avoid fluid restriction in patients with liver cirrhosis unless severe hyponatremia is present 2
   • May only prevent further decline rather than significantly correct sodium levels 3

2. Identify and treat underlying cause 1

   • Discontinue implicated medications (e.g., chemotherapeutic agents, opioids, NSAIDs, anticonvulsants, antidepressants) 1
   • Treat underlying malignancy if SIADH is paraneoplastic

Severe SIADH (Serum sodium <125 mEq/L) or Symptomatic Cases

1. Hypertonic 3% saline IV for life-threatening or acute symptomatic hyponatremia 1

   • Monitor sodium levels closely to prevent overly rapid correction
   • Limit correction to <8-10 mEq/L/24 hours to prevent osmotic demyelination 4

2. Pharmacologic options when fluid restriction fails:

   • Vasopressin-2 receptor antagonists (vaptans) 1, 5

     • Tolvaptan (starting dose 15 mg once daily, can increase to 30-60 mg) 5
     • Initiate in hospital setting with close monitoring 5
     • Avoid fluid restriction during first 24 hours of therapy 5
     • Monitor serum sodium at 0,6,24, and 48 hours 4
     • Limited to 30 days of treatment to minimize risk of liver injury 5

   • Demeclocycline (alternative option) 1, 6

   • Urea (alternative option) 1

   • Lithium (rarely used due to side effects) 1, 7

Special Considerations

Rate of Sodium Correction

• Critical safety concern: Limit correction to <8-10 mEq/L/24 hours 4
• Rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome, resulting in dysarthria, mutism, dysphagia, seizures, coma, or death 5
• Patients with malnutrition, alcoholism, or liver disease require slower correction rates 5

Vaptans Advantages and Monitoring

• No need for fluid restriction during treatment 4
• Faster and more reliable correction of hyponatremia 4
• Common side effects: thirst, polydipsia, increased urination 4
• Contraindicated in hypovolemic hyponatremia 5
• Monitor for hypernatremia, dehydration, and renal impairment 1
• Avoid in patients with altered mental status who cannot drink in response to thirst 1

Treatment Efficacy

• Fluid restriction alone may be insufficient in many cases, with >35% of patients failing to reach sodium levels ≥130 mEq/L after 3 days 3
• Vaptans have shown effectiveness in 45-82% of patients with hyponatremia 1

Long-term Management

• Continue fluid restriction as needed for chronic cases
• Consider intermittent use of pharmacologic therapies
• Monitor serum sodium regularly
• When discontinuing vaptans after >5-6 days, taper dose or implement fluid restriction to prevent hyponatremic relapse 4

Remember that treatment should be tailored based on the severity of hyponatremia, presence of symptoms, and rate of sodium correction to prevent neurological complications.