What is the treatment for hyponatremia secondary to inappropriate Antidiuretic Hormone (ADH) secretion?

Treatment of Hyponatremia Secondary to SIADH

For SIADH-induced hyponatremia, fluid restriction to 1 L/day is the cornerstone of treatment for mild-to-moderate cases, while 3% hypertonic saline is reserved for severe symptomatic hyponatremia with careful correction not exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1, 2

Initial Assessment and Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis of SIADH by verifying: 2, 3

• Hyponatremia (serum sodium <135 mmol/L) with hypoosmolality (plasma osmolality <275 mosm/kg)
• Inappropriately high urine osmolality (>500 mosm/kg)
• Inappropriately high urinary sodium (>20 mEq/L)
• Euvolemic state - this is critical, as absence of clinical hypovolemia or hypervolemia distinguishes SIADH from cerebral salt wasting or hypervolemic states 1, 3
• Normal thyroid, adrenal, and renal function 2, 3

A serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH. 1, 3

Treatment Algorithm Based on Symptom Severity

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

Administer 3% hypertonic saline immediately with a target correction of 6 mmol/L over 6 hours or until severe symptoms resolve. 1, 2, 3

Specific management: 1, 2

• Transfer to ICU for close monitoring
• Give 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals
• Monitor serum sodium every 2 hours initially
• Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome
• After initial 6 mmol/L correction, only 2 mmol/L additional correction is allowed in the next 18 hours

Mild Symptomatic or Asymptomatic Hyponatremia

Implement fluid restriction to 1 L/day as first-line therapy. 4, 1, 2, 3

Management steps: 1, 2

• Restrict fluids to 1000 mL/day
• Monitor serum sodium every 4 hours initially, then daily
• If no response after 24-48 hours, add oral sodium chloride 100 mEq three times daily
• Correction rate averages 1.0 mEq/L/day with fluid restriction alone

Avoid fluid restriction during the first 24 hours of hypertonic saline therapy - patients should continue fluid intake in response to thirst during acute correction. 5

Second-Line Pharmacological Options

If fluid restriction fails or is poorly tolerated: 4, 1, 2, 3

Urea (0.25-0.50 g/kg/day): 4, 6, 7

• Highly effective for chronic SIADH management
• Induces osmotic water drive
• Well-tolerated long-term, though distaste is common (54% of patients)
• Allows easier water and sodium control
• May permit decreased fluid restriction

Demeclocycline: 4, 2, 3

• Induces nephrogenic diabetes insipidus
• Reduces kidney's response to ADH
• Considered second-line when fluid restriction ineffective
• Long history of use but limited availability and safety concerns

Tolvaptan (vasopressin V2 receptor antagonist): 1, 5

• FDA-approved for clinically significant euvolemic hyponatremia (serum sodium <125 mEq/L)
• Starting dose: 15 mg once daily
• Titrate to 30 mg after 24 hours, maximum 60 mg daily
• Must initiate and re-initiate in hospital with close sodium monitoring
• Do not use for more than 30 days due to hepatotoxicity risk
• Correction rate approximately 3.0 mEq/L/day

Other options include lithium and loop diuretics, though these are less commonly used. 4, 3

Critical Correction Rate Guidelines

Never exceed 8 mmol/L correction in 24 hours for chronic hyponatremia. 4, 1, 2, 3, 5

High-risk patients require even slower correction (4-6 mmol/L per day): 1, 2, 3

• Advanced liver disease
• Alcoholism
• Severe malnutrition
• Prior encephalopathy

The FDA warns that correction >12 mEq/L/24 hours can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death. 5

Special Considerations and Common Pitfalls

Do NOT use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm - this worsens outcomes. 4, 1, 3 Consider fludrocortisone or hydrocortisone instead in these neurosurgical patients. 4, 1

Distinguish SIADH from cerebral salt wasting (CSW) - they require opposite treatments: 1, 2, 3

• SIADH: euvolemic, treat with fluid restriction
• CSW: hypovolemic (CVP <6 cm H₂O), treat with volume and sodium replacement
• Using fluid restriction in CSW worsens outcomes

Address the underlying cause: 2, 3

• Malignancy (especially small cell lung cancer)
• CNS disorders
• Pulmonary pathology
• Medications (SSRIs, carbamazepine, cyclophosphamide, vincristine, cisplatin)
• Discontinue offending medications when possible

After discontinuing tolvaptan, resume fluid restriction and monitor sodium levels closely. 5

Monitoring During Treatment

For severe symptoms: monitor serum sodium every 2 hours during initial correction. 1, 2, 3

For mild symptoms: monitor every 4 hours initially, then daily. 1, 2

Watch for signs of osmotic demyelination syndrome (typically 2-7 days after rapid correction): dysarthria, dysphagia, oculomotor dysfunction, quadriparesis. 1