What is the recommended treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and is desmopressin (DDAVP) used?

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Desmopressin is NOT a primary treatment for SIADH; rather, it is used to prevent overly rapid correction of hyponatremia during SIADH treatment. The primary treatments for SIADH include fluid restriction, vasopressin receptor antagonists (tolvaptan), and addressing underlying causes 1.

Diagnosis of SIADH

SIADH should be diagnosed based on established criteria:

• Hyponatremia (serum sodium <134 mEq/L)
• Hypoosmolality (plasma osmolality <275 mOsm/kg)
• Inappropriately high urine osmolality (>500 mOsm/kg)
• Inappropriately high urinary sodium concentration (>20 mEq/L)
• Clinical euvolemia
• Normal renal, adrenal, and thyroid function 1

Treatment Approach Based on Severity

Mild Hyponatremia (126-135 mEq/L)

• Continue diuretic therapy if already prescribed
• Monitor electrolytes
• No water restriction needed 1

Moderate Hyponatremia (120-125 mEq/L)

• Consider stopping diuretics, especially if creatinine is elevated
• Fluid restriction (1,000-1,500 mL/day)
• Adequate oral salt intake 1

Severe Hyponatremia (<120 mEq/L)

• Stop diuretics
• Consider volume expansion with colloid or saline for symptomatic patients
• For severe symptomatic hyponatremia (confusion, seizures), hypertonic (3%) saline may be required 1, 2

First-Line Treatments for SIADH

1. Identify and treat underlying cause (malignancies, CNS disorders, pulmonary diseases, medications)
2. Fluid restriction (1,000-1,500 mL/day)
3. Increase solute intake (salt, urea)
4. Pharmacological options:
   • Tolvaptan (vasopressin receptor antagonist): starting dose 15 mg once daily, titrated to 30 mg, then 60 mg as needed 1
   • Demeclocycline: can be used if fluid restriction is not tolerated 1

Role of Desmopressin in SIADH Management

Desmopressin is NOT used to treat SIADH directly. Instead, it has a paradoxical role:

• It is used to prevent overly rapid correction of hyponatremia during treatment of SIADH 2, 3
• It helps control the rate of serum sodium correction to prevent osmotic demyelination syndrome 4

There are three strategies for desmopressin administration during hyponatremia correction:

1. Proactive: administered early based on initial serum sodium concentration
2. Reactive: administered based on changes in serum sodium concentration or urine output
3. Rescue: administered after correction targets are exceeded 4, 5

Critical Safety Considerations

• Correction of serum sodium levels should not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1, 2
• When treating hyponatremia in SIADH, 0.9% saline should be avoided as it can act as a hypertonic solution and cause rapid fluctuations in serum sodium levels 2
• If a patient is receiving desmopressin for another indication and develops hyponatremia, do not withhold desmopressin despite the presence of hyponatremia, as this can lead to rapid changes in serum sodium levels 3

Monitoring During Treatment

• Regular monitoring of serum electrolytes and volume status
• More careful management in high-risk populations (malnutrition, alcoholism, advanced liver disease)
• After discontinuing tolvaptan, resume fluid restriction and monitor for changes in serum sodium 1

Pitfalls to Avoid

• Overly rapid correction of sodium (>8-10 mmol/L/day) can lead to osmotic demyelination syndrome
• Water restriction in patients with serum sodium >126 mmol/L is unnecessary and may worsen hypovolemia
• Tolvaptan is contraindicated in patients with ADPKD, those unable to sense or respond to thirst, hypovolemic hyponatremia, patients taking strong CYP3A inhibitors, anuria, and hypersensitivity to tolvaptan 1