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 treatment for mild to asymptomatic 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

Before initiating treatment, confirm the diagnosis by documenting:

• Hyponatremia (serum sodium <134-135 mEq/L) with plasma osmolality <275 mOsm/kg 2, 3
• Inappropriately concentrated urine (osmolality >100-500 mOsm/kg) with urine sodium >20 mEq/L 2, 4
• Euvolemic state (no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes) 1
• Normal thyroid and adrenal function to exclude other causes 3

Treatment Algorithm Based on Symptom Severity

Severe Symptomatic Hyponatremia (seizures, coma, altered mental status)

Immediate ICU transfer with close monitoring is mandatory. 2

• Administer 3% hypertonic saline as 100-150 mL IV bolus over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1, 5
• Target correction: 6 mmol/L over 6 hours or until severe symptoms resolve 1, 2
• Monitor serum sodium every 2 hours initially during active correction 1, 2
• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 1, 2, 6

Mild Symptomatic or Asymptomatic Hyponatremia

Fluid restriction is first-line therapy:

• Restrict fluids to 1 L/day (or 65-80% of calculated maintenance in pediatrics) 1, 2, 4
• If no response after adequate trial, add oral sodium chloride 100 mEq three times daily 1
• Monitor sodium levels every 4 hours initially, then daily 1

Avoid fluid restriction during the first 24 hours if using tolvaptan, and patients can drink to thirst. 6

Second-Line Pharmacological Options

When fluid restriction fails or is poorly tolerated:

Oral Urea

• Effective and safe second-line option for chronic SIADH 5
• Can be used as first pharmacological intervention alongside fluid restriction 1
• Monitor to ensure correction does not exceed 8 mmol/L in 24 hours 1

Vaptans (Vasopressin Receptor Antagonists)

Tolvaptan must be initiated and re-initiated only in hospital settings with close sodium monitoring. 6

• Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 6
• Do not use for more than 30 days due to hepatotoxicity risk 6
• Check serum sodium at 0,6,24, and 48 hours after initiation 7
• Contraindicated with strong CYP3A inhibitors, hypovolemic hyponatremia, and inability to sense thirst 6
• Side effects include thirst, polydipsia, and urinary frequency 7

Other Options (Less Commonly Used)

• Demeclocycline: Second-line agent for chronic SIADH when fluid restriction ineffective 2, 8
• Loop diuretics, lithium: Limited supporting data 8

Special Populations Requiring Cautious Correction

Patients at high risk for osmotic demyelination syndrome require slower correction rates of 4-6 mmol/L per day: 1, 2

• Advanced liver disease
• Severe malnutrition
• Alcoholism
• Chronic severe hyponatremia

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours:

• Immediately discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Consider administering desmopressin to slow or reverse the rapid rise 1
• Target reduction to bring total 24-hour correction to no more than 8 mmol/L from baseline 1

Critical Monitoring Parameters

• Serum sodium: Every 2 hours during severe symptomatic correction, every 4 hours after symptom resolution, then daily 1, 2
• Daily assessment of fluid balance, clinical status, urine output and osmolality 3
• Watch for osmotic demyelination syndrome signs (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically 2-7 days after rapid correction 1

Treatment of Underlying Cause

Always identify and treat the underlying etiology: 2

• Malignancy (especially small cell lung cancer)
• CNS disorders (meningitis, subarachnoid hemorrhage)
• Pulmonary disease
• Medications (carbamazepine, SSRIs, chemotherapy agents, NSAIDs) 2, 9

Successful treatment of the underlying cause often resolves SIADH. 2

Common Pitfalls to Avoid

• Never use fluid restriction in cerebral salt wasting (CSW), which requires volume and sodium replacement 1, 2
• Distinguishing SIADH (euvolemic) from CSW (hypovolemic) is critical, as treatments are fundamentally different 1, 2
• Inadequate monitoring during active correction can lead to osmotic demyelination 1, 2
• Ignoring mild hyponatremia (130-135 mmol/L) increases fall risk and mortality 1
• In subarachnoid hemorrhage patients at risk for vasospasm, avoid fluid restriction 2