Treatment of Euvolemic Hyponatremia

First-Line Treatment: Fluid Restriction

Fluid restriction to 1 L/day is the cornerstone of treatment for euvolemic hyponatremia (SIADH). 1

Implement strict fluid restriction of <1 L/day (1000 mL/day) as the initial therapeutic approach 1, 2
This addresses the underlying pathophysiology of impaired free water excretion due to inappropriate ADH activity 1
However, nearly half of SIADH patients do not respond adequately to fluid restriction alone 3
Compliance with fluid restriction is often poor, limiting its real-world effectiveness 1

When fluid restriction fails or is insufficient, two primary options exist:

Urea (0.5-1 g/kg/day) is considered a very effective and safe second-line treatment for SIADH. 3, 4

Dosing: 30-60 g/day administered orally or via gastric tube 4
In ICU studies, urea increased serum sodium from 128±4 mEq/L to 135±4 mEq/L within 2 days despite fluid intake >2 L/day 4
Urea is simple, inexpensive, and allows patients to drink freely in response to thirst 4, 2
Main limitation: poor palatability and potential gastric intolerance 2

Tolvaptan 15 mg once daily (titrated to 30-60 mg) is FDA-approved for euvolemic hyponatremia but requires hospital initiation. 5

Start at 15 mg once daily, increase after 24 hours to 30 mg, then to maximum 60 mg as needed 5
Must be initiated and re-initiated only in hospital with close serum sodium monitoring 5
Avoid fluid restriction during first 24 hours of tolvaptan therapy to prevent overly rapid correction 5
In clinical trials (SALT-1 and SALT-2), tolvaptan increased serum sodium by 3.7 mEq/L at Day 4 and 4.6 mEq/L at Day 30 compared to placebo (p<0.0001) 5
Do not use for more than 30 days due to hepatotoxicity risk 5
Main limitations: risk of overly rapid correction, increased thirst, and cost 2

For refractory cases, consider 1:

These options have more side effects and are less commonly recommended 6, 2

Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome. 1, 5

Target correction: 4-8 mmol/L per day for average-risk patients 1
For high-risk patients (advanced liver disease, alcoholism, malnutrition): limit to 4-6 mmol/L per day 1
Monitor serum sodium every 24 hours initially, then adjust frequency based on response 1
Too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination with devastating neurological consequences including dysarthria, dysphagia, quadriparesis, seizures, or death 5

Identify and treat underlying cause (malignancy, CNS disorders, pulmonary disease, medications like SSRIs or carbamazepine) 1, 7
Initiate fluid restriction <1 L/day with adequate solute intake (salt and protein) 1, 3
If no response after 48-72 hours, add oral urea 30-60 g/day OR consider tolvaptan 15 mg daily (hospital setting only) 3, 4
Monitor serum sodium daily during titration, then every 2-3 days once stable 1

Using fluid restriction in cerebral salt wasting (CSW) instead of SIADH—this worsens outcomes as CSW requires volume replacement 1
Inadequate monitoring during active correction—can lead to osmotic demyelination 1
Failing to identify and treat the underlying cause—SIADH is always secondary to another condition 1, 7
Ignoring mild hyponatremia (130-135 mmol/L)—even mild hyponatremia increases fall risk and mortality 1
Stopping fluid restriction when starting tolvaptan—this is actually correct practice, but clinicians often mistakenly continue restriction 5, 7

Neurosurgical patients: Distinguish SIADH from cerebral salt wasting (CSW), as CSW requires opposite treatment (volume and sodium replacement, not fluid restriction) 1
Subarachnoid hemorrhage patients at risk of vasospasm: Do not use fluid restriction; consider fludrocortisone or hydrocortisone instead 1
Adequate solute intake (salt and protein) should accompany fluid restriction to optimize effectiveness 3