How to manage a patient with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and hyponatremia?

Management of SIADH with Hyponatremia

For SIADH-induced hyponatremia, fluid restriction to 1 L/day is the cornerstone of treatment for mild-to-moderate 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 initiating treatment, confirm SIADH diagnosis with the following criteria 2:

• Hypotonic hyponatremia: Serum sodium <134 mEq/L with plasma osmolality <275 mosm/kg 2
• Inappropriately concentrated urine: Urine osmolality >500 mosm/kg despite low serum osmolality 2
• Elevated urinary sodium: >20 mEq/L (typically >40 mEq/L) 2
• Euvolemic state: No clinical signs of hypovolemia (orthostatic hypotension, dry mucous membranes) or hypervolemia (edema, ascites, jugular venous distention) 2
• Normal thyroid, adrenal, and renal function: Must exclude hypothyroidism and adrenal insufficiency 2

Critical distinction: Differentiate SIADH from cerebral salt wasting (CSW), particularly in neurosurgical patients, as CSW requires volume replacement rather than fluid restriction 1, 2. CSW presents with hypovolemia (CVP <6 cm H₂O) while SIADH shows euvolemia (CVP 6-10 cm H₂O) 2.

Treatment Algorithm Based on Symptom Severity

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

Immediate management 1, 2:

• Transfer to ICU for continuous monitoring 2
• Administer 3% hypertonic saline: 100-150 mL IV bolus over 10 minutes, repeatable up to 3 times at 10-minute intervals until symptoms improve 1, 3
• Target correction: 6 mmol/L increase over first 6 hours or until severe symptoms resolve 1, 2
• Maximum correction limit: 8 mmol/L in 24 hours (never exceed 12 mmol/L/24 hours) 1, 2, 4
• Monitoring frequency: Check serum sodium at 0,2,6,8, and 24 hours after initiation 1, 2
• Avoid fluid restriction during the first 24 hours to prevent overly rapid correction 4

Mild-to-Moderate Symptomatic or Asymptomatic Hyponatremia

First-line therapy 1, 2, 5:

• Fluid restriction to 1 L/day (500-1000 mL/day) 1, 2, 6
• Adequate solute intake: Encourage salt and protein intake 6
• Monitor response: Check serum sodium daily initially 2

Important caveat: Approximately 50% of SIADH patients do not respond adequately to fluid restriction alone 6. If serum sodium fails to improve after 48-72 hours, proceed to second-line therapy 6.

Second-Line Pharmacological Options

When fluid restriction fails 1, 2, 5:

• Oral urea: 15-30 grams daily in divided doses; highly effective and safe 6
• Oral sodium chloride: 100 mEq (approximately 6 grams) three times daily 1
• Demeclocycline: 600-1200 mg/day in divided doses for chronic SIADH 2, 5
• Tolvaptan (vaptan): Start 15 mg once daily, titrate to 30-60 mg as needed 4, 5

Tolvaptan-Specific Considerations

Initiation requirements 4:

• Must initiate in hospital setting with ability to monitor serum sodium closely 4
• Starting dose: 15 mg once daily without regard to meals 4
• Titration: Increase to 30 mg after 24 hours, then to 60 mg maximum as needed 4
• Critical monitoring: Check serum sodium at 0,6,8,24, and 48 hours after first dose 5
• Duration limit: Do not use for more than 30 days due to hepatotoxicity risk 4
• Avoid fluid restriction during first 24 hours; patients should drink to thirst 4

Contraindications for tolvaptan 4:

• Hypovolemic hyponatremia
• Concurrent use of strong CYP3A inhibitors
• Inability to sense or respond to thirst
• Anuria

Correction Rate Guidelines and Osmotic Demyelination Prevention

Standard correction limits 1, 2, 7:

• Maximum rate: 8 mmol/L per 24 hours for most patients 1, 2
• High-risk patients (advanced liver disease, alcoholism, malnutrition, severe hyponatremia <120 mEq/L): Limit to 4-6 mmol/L per day 1, 2
• Never exceed: 12 mmol/L in 24 hours under any circumstances 4, 7

If overcorrection occurs 1:

• Immediately discontinue hypertonic saline or tolvaptan 1
• Administer D5W (5% dextrose in water) to relower sodium 1
• Consider desmopressin (2-4 mcg IV/SC) to induce water retention 1
• Target: Bring total 24-hour correction back to ≤8 mmol/L from baseline 1

Special Populations and Pitfalls

Neurosurgical patients 1, 2:

• CSW is more common than SIADH in this population 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm 1, 2
• Consider fludrocortisone 0.1-0.2 mg daily for CSW 1, 2

Cancer patients with SIADH 2:

• Small cell lung cancer is the most common malignancy causing SIADH 2
• Treatment of underlying malignancy often resolves paraneoplastic SIADH 2
• Chemotherapy agents (cisplatin, vincristine) can worsen hyponatremia 2

Common pitfalls to avoid 1, 2:

• Using fluid restriction in CSW instead of SIADH worsens outcomes 1
• Inadequate monitoring during active correction leads to osmotic demyelination 1
• Failing to identify and treat the underlying cause 1, 2
• Ignoring mild hyponatremia (130-135 mmol/L), which increases fall risk and mortality 1

Monitoring and Follow-Up

During active treatment 1, 2:

• Severe symptoms: Check serum sodium every 2 hours initially 1
• After symptom resolution: Check every 4-6 hours 1
• Stable patients: Daily monitoring until target reached 2

Watch for osmotic demyelination syndrome 1, 7:

• Symptoms typically appear 2-7 days after rapid correction 1
• Manifestations include dysarthria, dysphagia, lethargy, quadriparesis, seizures 1, 7
• MRI shows characteristic pontine lesions 7

After discontinuation 4, 5:

• Resume fluid restriction 4
• Monitor for hyponatremic relapse, especially if tolvaptan used >5-6 days 5
• May need to taper vaptan dose rather than abrupt cessation 5