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

Treatment of SIADH

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

Diagnostic Confirmation Before Treatment

Before initiating treatment, confirm SIADH diagnosis with the following criteria 1:

• Hypotonic hyponatremia (serum sodium <134 mEq/L)
• Inappropriately high urine osmolality (>500 mosm/kg)
• Inappropriately high urinary sodium (>20 mEq/L)
• Euvolemic state (no edema, orthostatic hypotension, or volume depletion)
• Normal thyroid and adrenal function

Critical pitfall: Distinguish SIADH from cerebral salt wasting (CSW), as CSW requires volume replacement, not fluid restriction—using fluid restriction in CSW worsens outcomes 1, 2. CSW presents with hypovolemia (CVP <6 cm H₂O), while SIADH shows euvolemia (CVP 6-10 cm H₂O) 1.

Treatment Algorithm Based on Severity

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

Immediate ICU admission required 1:

• Administer 3% hypertonic saline IV
• Target: 6 mmol/L correction over 6 hours OR until severe symptoms resolve
• Monitor serum sodium every 2 hours initially 1
• Maximum correction: 8 mmol/L in 24 hours 1, 3

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

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

First-line treatment 1, 2:

• Fluid restriction to 1 L/day
• Monitor serum sodium every 24 hours initially
• Continue until sodium normalizes or underlying cause resolves

If fluid restriction fails after 48-72 hours, add 1:

• Oral sodium chloride 100 mEq three times daily
• Continue monitoring sodium levels daily

Chronic SIADH Refractory to Fluid Restriction

Second-line pharmacological options 1, 2:

Demeclocycline 1:

• Induces nephrogenic diabetes insipidus
• Effective when fluid restriction poorly tolerated
• Monitor renal function

Tolvaptan (FDA-approved vaptan) 3:

• Starting dose: 15 mg once daily
• Titrate to 30 mg after 24 hours, maximum 60 mg daily
• Must initiate in hospital with close sodium monitoring 3
• Limit use to 30 days maximum to minimize liver injury risk 3
• Avoid fluid restriction during first 24 hours of vaptan therapy 3
• Monitor sodium at 0,6,24, and 48 hours after initiation 4

Urea 1, 5:

• Effective alternative to vaptans
• Dose: 30-60 g/day in divided doses
• Better tolerated than demeclocycline in some patients

Treatment of Underlying Cause

Always address the root cause 1, 6:

• Discontinue offending medications (SSRIs, carbamazepine, cyclophosphamide, vincristine, NSAIDs, opioids) 1
• Treat underlying malignancy (especially SCLC) 1
• Manage CNS or pulmonary pathology 6, 7
• Hyponatremia typically improves after successful treatment of underlying cause 1

Critical Safety Monitoring

Prevent osmotic demyelination syndrome 1, 3:

• Never exceed 8 mmol/L correction in 24 hours for chronic hyponatremia
• Never exceed 12 mEq/L correction in 24 hours (FDA warning) 3
• Monitor for symptoms: dysarthria, dysphagia, lethargy, spastic quadriparesis, seizures 3
• Symptoms typically occur 2-7 days after rapid correction 2

If overcorrection occurs 2:

• Immediately discontinue hypertonic saline
• Switch to D5W (5% dextrose in water)
• Consider desmopressin to slow sodium rise
• Target: bring total 24-hour correction to ≤8 mmol/L

Special Populations

Neurosurgical patients with subarachnoid hemorrhage 1, 2:

• Avoid fluid restriction if at risk for vasospasm
• Consider fludrocortisone to prevent hyponatremia
• Hydrocortisone may prevent natriuresis

Cancer patients with paraneoplastic SIADH 1:

• Treat underlying malignancy as definitive therapy
• Use supportive measures (fluid restriction, vaptans) concurrently
• SIADH often resolves with successful cancer treatment

Post-Treatment Management

After discontinuing therapy 3:

• Resume fluid restriction
• Monitor serum sodium closely for rebound hyponatremia
• If stopping vaptans after >5-6 days, taper dose or restrict fluids 4
• Continue monitoring underlying cause

Common Pitfalls to Avoid

• Using fluid restriction in cerebral salt wasting instead of SIADH 1
• Inadequate monitoring during active correction 1, 2
• Overly rapid correction leading to osmotic demyelination 1, 3
• Failing to identify and treat underlying cause 1
• Administering hypotonic fluids (D5W) which worsen hyponatremia 1
• Ignoring mild hyponatremia (130-135 mmol/L)—even mild cases increase fall risk and mortality 2