How is Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion managed?

Management of SIADH

For SIADH, 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

Diagnostic Confirmation

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

• 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: no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 2
• Exclude hypothyroidism, adrenal insufficiency, and volume depletion 1
• Serum uric acid < 4 mg/dL has 73-100% positive predictive value for SIADH 1

Treatment Algorithm Based on Severity

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

Transfer to ICU immediately for close monitoring 1

• Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1
• Monitor serum sodium every 2 hours initially 1
• Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2
• For patients with malnutrition, alcoholism, or advanced liver disease, use even more cautious correction rates of 4-6 mmol/L per day 1

Mild Symptomatic or Asymptomatic Hyponatremia (Sodium < 120 mEq/L)

Fluid restriction to 1 L/day is first-line therapy 1, 2

• Discontinue any offending medications (SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, vincristine, NSAIDs, opioids) 1
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 2
• Monitor serum sodium every 4 hours initially, then daily 2
• Adequate solute intake (salt and protein) should be ensured 3

Moderate Hyponatremia (Sodium 120-125 mEq/L)

• Fluid restriction to 1-1.5 L/day 1
• Consider albumin infusion in hospitalized patients 1
• Monitor serum electrolytes closely 1

Second-Line Pharmacological Options

When fluid restriction fails or is poorly tolerated:

Demeclocycline

• Consider as second-line treatment for chronic SIADH 1
• Particularly useful when fluid restriction is ineffective 1

Tolvaptan (Vasopressin Receptor Antagonist)

• FDA-approved for clinically significant euvolemic hyponatremia 1
• Starting dose: 15 mg once daily, can be titrated to 30 mg after 24 hours, maximum 60 mg daily 1, 4
• Efficacy: Increases serum sodium by approximately 3.0 mEq/L/day 1
• In clinical trials, tolvaptan produced statistically greater increases in serum sodium compared to placebo (p <0.0001) 4
• Use with extreme caution: Close monitoring required to avoid overly rapid correction 1

Urea

• Effective and safe treatment option for SIADH 2, 3
• Can be used as first pharmacological intervention for mild to moderate SIADH 2
• Particularly valuable in neurosurgical patients 2

Other Options

• Furosemide with oral sodium supplementation 1
• Fludrocortisone (studied primarily in neurosurgical patients) 1

Special Considerations

Treatment of Underlying Cause

• Always identify and treat the underlying cause of SIADH (malignancy, CNS disorders, pulmonary disease, medications) 1
• In SCLC patients with paraneoplastic SIADH, treatment of the underlying malignancy is essential alongside hyponatremia management 1
• Hyponatremia usually improves after successful treatment of the underlying cause 1

Neurosurgical Patients

• Distinguish SIADH from cerebral salt wasting (CSW) as they require fundamentally different management 1, 2
• In subarachnoid hemorrhage patients at risk for vasospasm, avoid fluid restriction 1
• Consider fludrocortisone or hydrocortisone in these patients 1, 2

Critical Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis typically 2-7 days after rapid correction) 1
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting instead of SIADH 1
• Failing to recognize and treat the underlying cause 1
• Administering hypotonic fluids (such as D5W) which worsen hyponatremia by providing free water 1

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) 2
• Consider administering desmopressin to slow or reverse the rapid rise 2
• Target reduction to bring total 24-hour correction to no more than 8 mEq/L from starting point 2

Monitoring Parameters

• Severe symptoms: Serum sodium every 2 hours during initial correction 1
• After symptom resolution: Every 4 hours 2
• Chronic management: Daily monitoring to ensure correction does not exceed 8 mmol/L in 24 hours 2
• Watch for signs of osmotic demyelination syndrome 1