Treatment Options for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Fluid restriction to 1 L/day is the first-line treatment for asymptomatic or mild SIADH-induced hyponatremia, while hypertonic 3% saline is reserved for severe symptomatic cases with careful monitoring to prevent osmotic demyelination syndrome. 1
Diagnosis of SIADH
SIADH is characterized by:
- Hyponatremia (serum sodium < 134 mEq/L) 2
- Hypoosmolality (plasma osmolality < 275 mosm/kg) 2
- Inappropriately high urine osmolality (> 500 mosm/kg) 2
- Inappropriately high urinary sodium concentration (> 20 mEq/L) 2
- Absence of hypothyroidism, adrenal insufficiency, or volume depletion 2
Treatment Algorithm Based on Symptom Severity
Severe Symptomatic Hyponatremia (Mental status changes, seizures)
- Transfer to ICU for close monitoring 2
- Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 2, 1
- Monitor serum sodium every 2 hours initially 2
- Total correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 2, 3
- Calculate sodium deficit using formula: Desired increase in Na (mEq/L) × (0.5 × ideal body weight in kg) 2
- Once severe symptoms resolve, transition to mild symptomatic or asymptomatic protocol 2
Mild Symptomatic Hyponatremia (Nausea, vomiting, headache) or Asymptomatic with Na < 120 mEq/L
- Fluid restriction to 1 L/day 2, 1
- Monitor sodium every 4 hours 2
- If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 2
- Consider high protein diet 2
Asymptomatic Hyponatremia (Na 120-130 mEq/L)
Pharmacological Options for Refractory Cases
Vasopressin Receptor Antagonists (Vaptans)
- Tolvaptan is indicated for clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) 5
- Must be initiated in hospital setting with close monitoring 5
- Starting dose is 15 mg once daily, may increase to 30 mg after 24 hours, maximum 60 mg daily 5
- Do not administer for more than 30 days to minimize risk of liver injury 5
- Contraindicated in hypovolemic hyponatremia and in patients unable to sense or respond to thirst 5
Other Pharmacological Options
- Demeclocycline can be considered as second-line treatment 1, 6
- Fludrocortisone has been studied primarily in neurosurgical patients 2
- Urea has been used in some cases 2, 7
Special Considerations
Correction Rate
- For severe hyponatremia, correct by 6 mmol/L over 6 hours or until severe symptoms improve 2, 3
- Total correction should not exceed 8 mmol/L in 24 hours 2, 3
- For patients with malnutrition, alcoholism, or advanced liver disease, use more cautious correction rates (4-6 mmol/L per day) 3, 5
Efficacy of Different Treatments
- Fluid restriction produces modest increases in serum sodium (median 4 mmol/L after 30 days) 4
- Hypertonic saline and tolvaptan produce the greatest mean rate of sodium change (3.0 mEq/L/day) compared to isotonic saline (1.5 mEq/L/day) and fluid restriction (1.0 mEq/L/day) 8
- Fluid restriction fails to increase serum sodium by ≥5 mEq/L in 55% of treatment episodes 8
Common Pitfalls to Avoid
- Overly rapid correction leading to osmotic demyelination syndrome 3, 5
- Inadequate monitoring during active correction 3
- Using fluid restriction in cerebral salt wasting (CSW) instead of SIADH 3
- Failing to recognize and treat the underlying cause 1, 3
- Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 3