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

SIADH Management

For SIADH, fluid restriction to 1 L/day is the cornerstone of first-line treatment for mild to moderate 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

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm SIADH diagnosis with these criteria 2:

• Hypotonic hyponatremia (serum sodium <135 mEq/L, plasma osmolality <275 mOsm/kg)
• Inappropriately concentrated urine (urine osmolality >500 mOsm/kg despite low plasma osmolality)
• Elevated urine sodium (>20-40 mEq/L)
• Euvolemic state on clinical examination (no edema, orthostatic hypotension, or signs of volume depletion) 1, 2
• Normal thyroid, adrenal, and renal function 2

Critical pitfall: Distinguish SIADH from cerebral salt wasting (CSW) in neurosurgical patients, as they require opposite treatments—SIADH needs fluid restriction while CSW requires volume and sodium replacement 1, 3. CSW presents with true hypovolemia (CVP <6 cm H₂O) versus SIADH's euvolemia (CVP 6-10 cm H₂O) 3.

Treatment Algorithm Based on Symptom Severity

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

Immediate management 1, 2:

• Transfer to ICU for close monitoring 2
• Administer 3% hypertonic saline as 100-150 mL IV bolus over 10 minutes, repeatable up to 3 times at 10-minute intervals 1
• 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 this to prevent osmotic demyelination syndrome) 1, 2, 4
• Monitor serum sodium every 2 hours during initial correction 1, 2

Special populations requiring slower correction (4-6 mmol/L per day maximum) 1, 2:

• Advanced liver disease
• Alcoholism or severe malnutrition
• Prior encephalopathy
• Chronic hyponatremia (>48 hours duration)

Mild to Moderate Symptomatic or Asymptomatic SIADH

First-line therapy: Fluid restriction 1, 2, 5:

• Restrict fluids to 1 L/day (1000 mL/24 hours) 1, 2
• Avoid fluid restriction during first 24 hours if using tolvaptan to prevent overly rapid correction 4
• This achieves correction rate averaging 1.0 mEq/L/day 5
• Monitor serum sodium every 24 hours initially 1

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

• Oral sodium chloride 100 mEq (approximately 6 grams) three times daily 1
• Adequate solute intake (salt and protein) 6

Second-Line Pharmacological Options

When fluid restriction proves ineffective (occurs in approximately 50% of SIADH patients) 6:

Vasopressin receptor antagonists (Vaptans) 4:

• Tolvaptan starting dose: 15 mg once daily orally 4
• Titrate at 24-hour intervals to 30 mg, then 60 mg once daily as needed 4
• Critical monitoring: Check serum sodium at 0,6,24, and 48 hours after initiation to prevent overcorrection 5
• Limit duration to 30 days maximum to minimize hepatotoxicity risk 4
• Contraindications: Hypovolemic hyponatremia, inability to sense thirst, anuria, concurrent strong CYP3A inhibitors 4
• Tolvaptan increased serum sodium by 4.0 mEq/L at Day 4 and 6.2 mEq/L at Day 30 versus placebo (0.4 and 1.8 mEq/L respectively) 4

Oral urea 1, 6:

• Considered very effective and safe second-line treatment 6
• Particularly valuable when combined with fluid restriction 1
• Dose: 30-60 grams daily in divided doses 1

Demeclocycline 2, 5, 7:

• Induces nephrogenic diabetes insipidus, reducing kidney's response to ADH 5
• Reserved for chronic SIADH refractory to other measures 2, 7
• Dose: 600-1200 mg daily in divided doses 7

Loop diuretics (furosemide) 1, 7:

• Can be used with hypertonic saline in acute symptomatic cases to produce negative free-water balance 7
• Less commonly used for chronic management 1

Special Considerations

Neurosurgical patients with subarachnoid hemorrhage at risk for vasospasm 1, 2, 3:

• Never use fluid restriction—this worsens outcomes 1, 3
• Consider fludrocortisone 0.1-0.2 mg daily to prevent vasospasm 1, 3
• Consider hydrocortisone to prevent natriuresis 1

Cancer patients with paraneoplastic SIADH 2:

• Treatment of underlying malignancy is essential alongside hyponatremia management 2
• Small cell lung cancer is the most common malignancy causing SIADH 2

Medication-induced SIADH 8, 9:

• Discontinue offending agents: SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, vincristine, NSAIDs, opioids 8, 9
• This alone may resolve hyponatremia 9

Critical Safety Principles

Osmotic demyelination syndrome prevention 1, 2, 4, 5:

• Never exceed 8-10 mmol/L correction in 24 hours 1, 5
• In high-risk patients (liver disease, alcoholism, malnutrition), limit to 4-6 mmol/L per day 1, 2
• Symptoms of osmotic demyelination appear 2-7 days post-correction: dysarthria, dysphagia, dysphagia, lethargy, spastic quadriparesis, seizures, coma 1, 4

If overcorrection occurs 1:

• Immediately discontinue hypertonic saline or vaptan
• Switch to D5W (5% dextrose in water) 1
• Consider desmopressin to slow sodium rise 1
• Goal: bring total 24-hour correction back to ≤8 mmol/L 1

Monitoring requirements 1, 2, 5:

• Severe symptoms: serum sodium every 2 hours initially 1, 2
• Mild symptoms: serum sodium every 4-6 hours initially 1
• After vaptan initiation: 0,6,24, and 48 hours 5
• Chronic management: every 24-48 hours until stable 1

Common Pitfalls to Avoid

• Using fluid restriction in cerebral salt wasting instead of SIADH—this worsens outcomes 1, 2
• Inadequate monitoring during active correction leading to overcorrection 1, 2
• Failing to identify and treat underlying cause (malignancy, medications, CNS disorders) 2, 8
• Correcting chronic hyponatremia too rapidly (>8 mmol/L/24 hours) 1, 5
• Using hypertonic saline in patients who can tolerate slower correction with fluid restriction 1, 8