What is the primary management for a patient with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Primary Management of SIADH

Fluid restriction to 1 liter per day is the cornerstone of treatment for patients with mild to moderate SIADH who are asymptomatic or have only mild symptoms. 1

Initial Assessment and Diagnosis

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

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

A critical pitfall is failing to distinguish SIADH from cerebral salt wasting (CSW), particularly in neurosurgical patients, as CSW requires volume replacement rather than fluid restriction and using fluid restriction in CSW can be hazardous and worsen outcomes. 1, 2

Treatment Algorithm Based on Symptom Severity

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

For life-threatening symptoms, immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until severe symptoms resolve. 1, 3

• Transfer to ICU for close monitoring 1
• Administer 3% hypertonic saline as 100-150 mL IV boluses over 10 minutes, repeatable up to three times at 10-minute intervals 3
• Monitor serum sodium every 2 hours during initial correction 1
• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 1, 3

Mild Symptomatic or Asymptomatic SIADH (Sodium 120-134 mEq/L)

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

• Avoid fluid restriction during the first 24 hours if using pharmacologic therapy to prevent overly rapid correction 4
• If no response to fluid restriction after 48-72 hours, add oral sodium chloride 100 mEq three times daily 1
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response 1

Second-Line Pharmacological Options

When fluid restriction fails or is poorly tolerated (occurs in approximately 50% of SIADH patients 5):

Demeclocycline

• Dose: 600-1200 mg/day divided in 2-4 doses 1, 6
• Induces nephrogenic diabetes insipidus, reducing kidney's response to ADH 1
• Long history of use in persistent SIADH cases 1

Urea

• Dose: 30-60 g/day orally 1, 5
• Considered very effective and safe in recent literature 1, 5
• Particularly valuable in neurosurgical patients 1

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan: Start 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 1, 4
• FDA-approved for clinically significant euvolemic hyponatremia 1, 4
• Produces statistically greater increase in serum sodium compared to placebo (3.0 mEq/L/day) 1, 4
• Critical monitoring: Check serum sodium at 0,6,24, and 48 hours after initiation to prevent overcorrection 7
• Use with extreme caution in cirrhosis due to higher risk of gastrointestinal bleeding (10% vs 2% placebo) 3

Correction Rate Guidelines

The single most important safety principle: never exceed 8 mmol/L correction in 24 hours. 1, 3

• Standard correction rate: 4-8 mmol/L per day 3
• High-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy): 4-6 mmol/L per day maximum 1, 3
• Chronic hyponatremia (>48 hours): Do not correct faster than 1 mmol/L/hour 3

Treatment of Underlying Cause

Always identify and treat the underlying etiology of SIADH. 1

Common causes requiring specific management:

• Medications: Discontinue offending agents (SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, vincristine, NSAIDs, opioids) 1
• Malignancy: Particularly small cell lung cancer—treatment of underlying cancer often resolves paraneoplastic SIADH 1
• CNS disorders: Meningitis, encephalitis, subarachnoid hemorrhage 1, 2
• Pulmonary pathology: Pneumonia, tuberculosis 1

Special Populations

Neurosurgical Patients

• Never use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm—this worsens outcomes 1, 3
• Consider fludrocortisone 0.1-0.2 mg daily to prevent vasospasm 1, 3
• Distinguish SIADH (euvolemic, CVP 6-10 cm H₂O) from CSW (hypovolemic, CVP <6 cm H₂O) 1

Cirrhotic Patients

• More cautious correction rates (4-6 mmol/L per day) due to higher risk of osmotic demyelination 1, 3
• Avoid vaptans due to increased bleeding risk 3

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) 3
• Consider administering desmopressin to slow or reverse rapid rise 3
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 3

Common Pitfalls to Avoid

• Using fluid restriction in cerebral salt wasting instead of SIADH—this can be hazardous 1, 2
• Inadequate monitoring during active correction—check sodium frequently 1
• Overly rapid correction leading to osmotic demyelination syndrome 1, 3
• Failing to recognize and treat the underlying cause 1
• Ignoring mild hyponatremia (130-135 mmol/L)—even mild hyponatremia increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1, 3