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

Treatment of SIADH

For SIADH, fluid restriction to 1 L/day is the cornerstone of treatment for mild to moderate cases, while severe symptomatic hyponatremia requires immediate 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1, 2

Initial Assessment and Diagnosis Confirmation

Before initiating treatment, confirm SIADH diagnosis with the following criteria 2:

• Hyponatremia (serum sodium <134-135 mEq/L) with hypoosmolality (plasma osmolality <275 mosm/kg) 2
• Inappropriately high urine osmolality (>500 mosm/kg) despite low serum osmolality 2
• Elevated urinary sodium (>20 mEq/L) 2
• Euvolemic state (no edema, normal skin turgor, moist mucous membranes, no orthostatic hypotension) 1, 2
• Normal thyroid, adrenal, and renal function 2

Critical distinction: Differentiate SIADH from cerebral salt wasting (CSW), as treatment approaches are opposite. CSW patients are hypovolemic with CVP <6 cm H₂O, while SIADH patients are euvolemic with CVP 6-10 cm H₂O. 1, 3

Treatment Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

Immediate management 1, 2:

• Transfer to ICU for close monitoring 1, 2
• Administer 3% hypertonic saline as 100-150 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals 1, 4
• Target correction: 6 mmol/L over first 6 hours or until severe symptoms resolve 1, 2
• Maximum correction limit: 8 mmol/L in 24 hours (never exceed 12 mmol/L/24 hours) 1, 2, 5
• Monitor serum sodium every 2 hours initially 1, 2

High-risk patients (severe malnutrition, alcoholism, advanced liver disease) require even slower correction at 4-6 mmol/L per day 1, 2, 5

Mild Symptomatic or Asymptomatic Hyponatremia (Sodium <120 mEq/L)

First-line treatment 1, 2:

• Fluid restriction to 1 L/day 1, 2, 4
• Avoid fluid restriction during the first 24 hours if using tolvaptan 5
• Patients can continue fluid intake in response to thirst 5
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response 2

If fluid restriction fails (approximately 50% of SIADH patients do not respond) 4:

• Add oral sodium chloride 100 mEq three times daily 1
• Consider oral urea as highly effective second-line therapy 4, 6
• Demeclocycline 300-600 mg twice daily as alternative second-line option 2, 3, 7

Pharmacological Options for Refractory Cases

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan is FDA-approved for clinically significant euvolemic hyponatremia (serum sodium <125 mEq/L or symptomatic) 5:

• Starting dose: 15 mg once daily 5
• Titrate to 30 mg after at least 24 hours, maximum 60 mg daily 5
• Must initiate in hospital with close serum sodium monitoring 5
• Do not use for more than 30 days due to hepatotoxicity risk 5
• Monitor serum sodium at 0,6,24, and 48 hours after initiation 8
• Contraindicated with strong CYP3A inhibitors 5

Advantages: No fluid restriction needed, reliable correction within short time 8

Side effects: Thirst, polydipsia, frequent urination 8

Alternative Pharmacological Agents

• Urea: Very effective and safe for chronic SIADH, allows easier water and sodium control with decreased fluid restriction 4, 6
• Demeclocycline: 300-600 mg twice daily for chronic SIADH when fluid restriction is ineffective or poorly tolerated 2, 3
• Lithium and loop diuretics: Limited data supporting use 7

Treatment of Underlying Cause

Address the root cause 2, 7:

• Discontinue offending medications (carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, vincristine, cisplatin, vinca alkaloids) 7
• Treat underlying malignancy (particularly small cell lung cancer) 2
• Manage CNS disorders or pulmonary disease 2

Critical Safety Considerations and Monitoring

Osmotic demyelination syndrome prevention 1, 2, 5:

• Never exceed 8 mmol/L correction in 24 hours for chronic hyponatremia 1, 2
• Limit correction to 1 mmol/L/hour maximum 1
• In high-risk patients, limit to 4-6 mmol/L per day 1, 2, 5

Monitoring protocol 1, 2:

• Severe symptoms: Check serum sodium every 2 hours during initial correction 1, 2
• After symptom resolution: Every 4 hours 1
• Mild symptoms: Every 24 hours initially 2

Calculate sodium deficit: Desired increase in Na (mEq/L) × (0.5 × ideal body weight in kg) 1

Special Populations

Neurosurgical patients with subarachnoid hemorrhage 1, 2, 3:

• Avoid fluid restriction if at risk for vasospasm 1, 2, 3
• Consider fludrocortisone or hydrocortisone to prevent natriuresis 1, 3
• Distinguish from cerebral salt wasting, which requires volume replacement, not restriction 1, 3

Pediatric patients 9:

• Fluid restriction is vital in meningitis or postoperative settings 9
• Hypertonic saline reserved only for severely symptomatic patients 9

Common Pitfalls to Avoid

• Using fluid restriction in cerebral salt wasting instead of SIADH worsens outcomes and can be fatal 1, 3
• Overly rapid correction (>8 mmol/L/24 hours) causes osmotic demyelination syndrome 1, 2, 5
• Inadequate monitoring during active correction leads to overcorrection 1, 2
• Failing to treat underlying cause results in persistent hyponatremia 1, 2
• Administering hypotonic fluids (D5W, lactated Ringer's) worsens hyponatremia 3

Post-Treatment Management

Following discontinuation of therapy 5, 8:

• Resume fluid restriction 5
• Monitor for hyponatremic relapse, especially after vaptan discontinuation >5-6 days 8
• May need to taper vaptan dose or restrict fluid intake 8
• Continue monitoring serum sodium and volume status 5