Management of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
The management of SIADH should be guided by symptom severity, with fluid restriction as first-line therapy for mild to moderate cases and hypertonic saline for severe symptomatic cases, while ensuring correction rates do not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1, 2
Diagnosis of SIADH
- SIADH is characterized by hyponatremia (serum sodium < 134 mEq/L), hypoosmolality (plasma osmolality < 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and inappropriately high urinary sodium concentration (> 20 mEq/L) in the absence of hypothyroidism, adrenal insufficiency, or volume depletion 1
- Clinically significant hyponatremia requiring evaluation and treatment is generally considered when serum sodium is lower than 130-131 mmol/L 3
- Assessment of volume status is critical to differentiate SIADH (euvolemic) from other causes of hyponatremia such as cerebral salt wasting (hypovolemic) 3, 1
Treatment Algorithm Based on Symptom Severity
Severe Symptomatic Hyponatremia (life-threatening symptoms)
- Transfer to ICU for close monitoring 1
- Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve 1, 2
- Monitor serum sodium every 2 hours initially 1
- Total correction should 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 more cautious correction rates (4-6 mmol/L per day) 2, 4
Mild Symptomatic or Asymptomatic Hyponatremia
- Fluid restriction to 1 L/day as first-line treatment 1, 2
- Monitor sodium levels every 4-6 hours initially 2
- Address underlying causes of SIADH when possible 1, 2
Second-Line Treatment Options
Pharmacological Options
- Demeclocycline can be considered as second-line treatment for SIADH when fluid restriction is ineffective 1, 5
- Urea is an effective and safe treatment option for chronic SIADH 6
- Vasopressin receptor antagonists (vaptans):
- Tolvaptan is indicated for clinically significant euvolemic hyponatremia, including SIADH 4
- Must be initiated in a hospital setting where serum sodium can be closely monitored 4
- Starting dose is 15 mg once daily, which can be increased to 30 mg after 24 hours, and up to 60 mg if needed 4
- Should not be used for more than 30 days due to risk of liver injury 4
- Contraindicated in patients unable to sense or respond to thirst, hypovolemic hyponatremia, or those taking strong CYP3A inhibitors 4
Special Considerations for Specific Patient Populations
- In patients with subarachnoid hemorrhage (SAH) at risk for vasospasm, fluid restriction should be avoided 3
- Fludrocortisone may be considered in neurosurgical patients with SIADH 1
- In SCLC patients with paraneoplastic SIADH, treatment of the underlying malignancy is important alongside hyponatremia management 3, 7
Monitoring and Prevention of Complications
- Too rapid correction of hyponatremia (> 12 mEq/L/24 hours) can cause osmotic demyelination syndrome resulting in serious neurological sequelae 4
- During treatment with tolvaptan, avoid fluid restriction during the first 24 hours of therapy 4
- Following discontinuation of tolvaptan, patients should resume fluid restriction and be monitored for changes in serum sodium 4
- For chronic SIADH, limit the daily increase of serum sodium to less than 8-10 mmol/L 5
Common Pitfalls to Avoid
- Overly rapid correction leading to osmotic demyelination syndrome 1, 4
- Inadequate monitoring during active correction 1
- Using fluid restriction in cerebral salt wasting (CSW) instead of SIADH 1
- Failing to recognize and treat the underlying cause 1, 2
- Discontinuing vaptan therapy abruptly without monitoring for hyponatremic relapse 5
Treatment Efficacy and Outcomes
- Even mild hyponatremia is associated with increased hospital stay and mortality 8
- Hyponatremic patients with improvement in sodium levels have better outcomes than those without improvement 3
- Almost half of SIADH patients do not respond to fluid restriction as first-line therapy, necessitating consideration of second-line options 6