What is the treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Treatment for SIADH

For SIADH, the cornerstone of treatment is fluid restriction to 1 L/day 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

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm SIADH diagnosis with the following criteria 1:

• Hyponatremia (serum sodium < 134 mEq/L) with plasma osmolality < 275 mosm/kg 1
• Inappropriately high urine osmolality (> 500 mosm/kg) and urine sodium (> 20 mEq/L) 1
• Euvolemic state - absence of clinical signs of hypovolemia (orthostatic hypotension, dry mucous membranes) or hypervolemia (edema, ascites, jugular venous distention) 1
• Normal thyroid, adrenal, and renal function to exclude other causes 1

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

Treatment Algorithm Based on Severity

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

Immediate ICU admission with the following protocol 1:

• Administer 3% hypertonic saline as 100 mL IV bolus over 10 minutes, repeatable up to 3 times at 10-minute intervals until symptoms improve 1, 2
• 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, 3
• Monitor serum sodium every 2 hours during initial correction phase 1, 2
• Avoid fluid restriction during first 24 hours to prevent overly rapid correction 1, 3

Mild-to-Moderate Asymptomatic or Mildly Symptomatic SIADH

First-line treatment 1, 4:

• Fluid restriction to 1 L/day (500-1000 mL/day) is the cornerstone of chronic SIADH management 1, 4
• Adequate solute intake with salt and protein supplementation 4
• Monitor serum sodium daily initially, then adjust frequency based on response 1

Important caveat: Nearly 50% of SIADH patients do not respond adequately to fluid restriction alone 4

Second-Line Pharmacological Options (When Fluid Restriction Fails)

Oral urea 1, 4:

• Considered very effective and safe for chronic SIADH 4
• Dosing: 30-60 g/day in divided doses 1
• Particularly valuable in neurosurgical patients 1

Tolvaptan (vasopressin V2-receptor antagonist) 3:

• FDA-approved for clinically significant euvolemic hyponatremia 1, 3
• Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 1, 3
• Must initiate in hospital setting with close sodium monitoring 3
• Increases serum sodium by approximately 3.0 mEq/L/day 1
• Duration limit: Do not use for more than 30 days due to hepatotoxicity risk 3
• Contraindicated in: Hypovolemic hyponatremia, patients unable to sense thirst, those taking strong CYP3A inhibitors 3

Demeclocycline 1:

• Second-line option when fluid restriction ineffective or poorly tolerated 1
• Less commonly used due to side effects 5, 6

Special Populations Requiring Cautious Correction

High-risk patients require slower correction rates of 4-6 mmol/L per day 1, 2:

• Advanced liver disease or cirrhosis 1, 2
• Chronic alcoholism 1, 2
• Severe malnutrition 1, 2, 3
• Hypokalemia, hypophosphatemia 2

Treatment of Underlying Cause

Always identify and treat the underlying etiology 1:

• Malignancy (especially small cell lung cancer) - treat underlying cancer 1
• Medications - discontinue offending agents (SSRIs, carbamazepine, cyclophosphamide, vincristine, cisplatin) 1
• CNS disorders - address neurological pathology 1
• Pulmonary disease - treat underlying lung condition 1

Critical Pitfalls to Avoid

Never exceed 8 mmol/L correction in 24 hours - this causes osmotic demyelination syndrome with devastating neurological consequences (dysarthria, dysphagia, quadriparesis, seizures, coma, death) 1, 2, 3

Do not use fluid restriction in cerebral salt wasting - this is a different entity requiring volume and sodium replacement, not restriction 1, 2

Avoid fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm - this worsens outcomes 1, 2

Do not use tolvaptan in hypovolemic hyponatremia - it is contraindicated and will worsen the condition 3

Monitoring During Treatment

• Severe symptoms: Check sodium every 2 hours initially 1, 2
• Mild symptoms: Check sodium every 4 hours after symptom resolution 2
• Chronic management: Daily sodium checks initially, then adjust based on stability 1
• Watch for osmotic demyelination syndrome 2-7 days after correction (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) 1, 2

Management of Overcorrection

If sodium rises >8 mmol/L in 24 hours 1, 2:

• Immediately discontinue hypertonic saline and switch to D5W (5% dextrose in water) 1, 2
• Administer desmopressin to slow or reverse rapid sodium rise 1, 2
• Target relowering to bring total 24-hour correction to ≤8 mmol/L 1, 2