What additional medications can be used to raise serum sodium in a patient with hyponatremia, such as SIADH?

Pharmacological Options for Raising Serum Sodium in Hyponatremia

For SIADH and euvolemic hyponatremia refractory to fluid restriction, oral sodium chloride tablets (100 mEq three times daily) are the first-line pharmacological option, while vasopressin receptor antagonists (tolvaptan 15 mg daily, titrated to 30-60 mg) serve as second-line therapy when salt supplementation fails. 1

Oral Sodium Chloride Supplementation

• Sodium chloride tablets at 100 mEq (approximately 2.3 grams) three times daily should be added when fluid restriction alone does not adequately correct hyponatremia in SIADH patients 1
• Each 1 gram of sodium chloride contains approximately 17 mEq of sodium, allowing for precise dosing calculations 1
• This approach delivers approximately 7 grams of sodium per day total, which can effectively raise serum sodium when combined with fluid restriction 1
• Hourly oral sodium chloride administration can provide a graded and predictable increase in serum sodium, offering an alternative to intravenous hypertonic saline in selected patients with severe hyponatremia who cannot access ICU care 2

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan Dosing and Efficacy

• Start tolvaptan at 15 mg orally once daily, then titrate to 30 mg after at least 24 hours if needed, with a maximum dose of 60 mg daily 3
• Tolvaptan significantly increases serum sodium compared to placebo in patients with euvolemic or hypervolemic hyponatremia, with effects seen as early as 8 hours after the first dose 1, 3
• In clinical trials, tolvaptan increased average serum sodium by 3.7 mEq/L at Day 4 and 4.6 mEq/L at Day 30 compared to placebo (p<0.0001) 3
• For patients with baseline sodium <130 mEq/L, the effect was even more pronounced: 4.2 mEq/L at Day 4 and 5.5 mEq/L at Day 30 versus placebo 3

Critical Monitoring Requirements

• Check serum sodium every 2 hours during the first 8 hours after the initial tolvaptan dose to prevent overcorrection 1
• Avoid fluid restriction during the first 24 hours of tolvaptan therapy to prevent overly rapid correction of serum sodium 3
• Patients require adequate free-water intake to replace urinary water losses; inadequate oral intake can lead to treatment failure and hypernatremia 1

Special Populations and Cautions

• In cirrhotic patients, use tolvaptan with extreme caution due to higher risk of gastrointestinal bleeding (10% vs 2% with placebo) and hepatotoxicity (4.4% developed ALT >3× upper limit of normal) 1
• Tolvaptan should be limited to ≤30 days of use and reserved for highly selected patients, such as those with severe symptomatic hyponatremia refractory to standard measures 1
• Liver function tests should be monitored monthly during tolvaptan therapy to detect early hepatotoxicity 1

Urea as an Alternative Agent

• Oral urea is considered a very effective and safe second-line treatment for SIADH, alongside diuretics, lithium, and demeclocycline 1, 4
• Urea can be used as the first pharmacological intervention for mild to moderate SIADH after fluid restriction fails 1
• In neurosurgical patients, a dose of 40 grams of urea in 100-150 mL of normal saline every 8 hours has been effective in treating hyponatremia 1

Loop Diuretics

• Loop diuretics (furosemide) may be considered as a treatment option for euvolemic hyponatremia (SIADH) by promoting free water excretion 1
• Diuretics are particularly useful when combined with adequate salt intake to prevent excessive sodium loss 1

Fludrocortisone for Cerebral Salt Wasting

• Fludrocortisone 0.1-0.2 mg daily is recommended for cerebral salt wasting (CSW) in neurosurgical patients, particularly those with subarachnoid hemorrhage at risk of vasospasm 1
• Fludrocortisone reduces renal sodium losses and helps maintain serum sodium levels in CSW 1
• Hydrocortisone may also prevent natriuresis in subarachnoid hemorrhage patients with CSW 1

Critical Safety Considerations

Correction Rate Limits

• Never exceed 8 mmol/L correction in any 24-hour period to prevent osmotic demyelination syndrome, regardless of which medication is used 1, 5
• High-risk patients (advanced liver disease, alcoholism, malnutrition) require even slower correction at 4-6 mmol/L per day maximum 1, 5
• Monitor serum sodium every 2-4 hours during active correction to prevent overcorrection 1

Management of Overcorrection

• If sodium rises too rapidly (>8 mmol/L in 24 hours), immediately administer D5W (5% dextrose in water) and desmopressin to slow or reverse the increase 5
• Target reduction of sodium by 2-4 mEq/L over 6-8 hours to bring total 24-hour correction back to ≤8 mEq/L from baseline 5

Common Pitfalls to Avoid

• Do not use tolvaptan as first-line therapy before exhausting fluid restriction and oral sodium supplementation 1
• Avoid potassium-containing salt substitutes when using oral sodium chloride, as patients are at risk for hyperkalemia 1
• Do not apply fluid restriction during the first 24 hours of tolvaptan therapy, as this increases the risk of overly rapid sodium correction 1, 3
• Never use these medications in cerebral salt wasting without concurrent volume replacement, as CSW requires volume and sodium repletion, not fluid restriction 1