From the Guidelines
For a 79-year-old patient with chronic euvolemic hyponatremia consistent with SIADH who has not responded to normal saline, I recommend tolvaptan starting at 15 mg daily as the most effective treatment option, given its ability to improve serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH, as supported by the most recent and highest quality study 1. The patient's low urine osmolality (195 mOsm/kg) and lack of response to gentle IV normal saline suggest that a pharmacologic approach may be necessary. Key considerations for treatment include:
- The severity of hyponatremia: treatment should be initiated when serum sodium is lower than 130 mmol/L, although there is no good evidence regarding the level of serum sodium at which treatment should be initiated 1.
- Patient compliance ability: the choice of treatment should take into account the patient's ability to adhere to the treatment regimen.
- Comorbidities: the presence of comorbidities, such as heart failure or cirrhosis, may influence the choice of treatment. Some potential benefits and risks of tolvaptan include:
- Improved serum sodium concentration: tolvaptan has been shown to improve serum sodium concentration in patients with hypervolemic hyponatremia, including those with SIADH 1.
- Increased urine volume and solute-free water excretion: tolvaptan increases urine volume and solute-free water excretion, which can help to correct hyponatremia 1.
- Risk of overly rapid correction: tolvaptan can cause overly rapid correction of serum sodium concentration, which can lead to central pontine myelinolysis or seizures, and therefore requires careful monitoring and titration 1. Regular monitoring of serum sodium, renal function, and volume status is essential with any treatment approach, particularly when using tolvaptan, to prevent overly rapid correction and to adjust the treatment regimen as needed. Other treatment options, such as fluid restriction, oral urea, and salt tablets combined with loop diuretics, may also be considered, but tolvaptan is the most effective option based on the available evidence. It is also important to note that demeclocycline, another potential treatment option, carries a higher risk of nephrotoxicity in elderly patients and is therefore not the preferred choice in this case.
From the FDA Drug Label
Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.
Treatment options for improving sodium in a 79-year-old patient with chronic euvolemic hyponatremia include:
- Tolvaptan, a vasopressin receptor antagonist, which can be initiated at a dose of 15 mg once daily and titrated up to 60 mg once daily as needed.
- Key considerations:
- Tolvaptan should be initiated and re-initiated in a hospital where serum sodium can be monitored closely.
- Too rapid correction of hyponatremia can cause osmotic demyelination, so the dose should be increased gradually.
- The patient should be advised to continue ingestion of fluid in response to thirst during the first 24 hours of therapy.
- Fluid restriction can be resumed or initiated after the first 24 hours of therapy as clinically indicated.
- The patient should be monitored for changes in serum electrolytes and volume during initiation and titration of tolvaptan.
- Tolvaptan is contraindicated in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of the FDA-approved REMS, and in patients who are unable to sense or respond to thirst.
- Tolvaptan can cause serious neurologic sequelae if serum sodium is corrected too rapidly, so careful monitoring is necessary 2.
- Studies have shown that tolvaptan can effectively increase serum sodium levels in patients with euvolemic or hypervolemic hyponatremia, including those with SIADH 2.
- Tolvaptan has been shown to be effective in patients with serum sodium <130 mEq/L or <125 mEq/L, with significant increases in serum sodium at Day 4 and Day 30 2.
From the Research
Treatment Options for Euvolemic Hyponatremia
The patient's condition of chronic euvolemic hyponatremia with no improvement after gentle IV normal saline and no offending medications, normal TSH and cortisol levels, and no clear explanation for a chronic SIADH picture, presents a challenge. Considering the provided evidence, the following treatment options can be explored:
- Vasopressin Receptor Antagonists (VRAs): Studies have shown that VRAs are effective in treating euvolemic and hypervolemic hyponatremia 3, 4. They work by antagonizing the action of vasopressin, leading to increased urine output and correction of serum sodium levels.
- Free Water Restriction: This is a common approach for managing euvolemic hyponatremia, especially in cases of SIADH 5, 6. Restricting free water intake can help increase serum sodium levels.
- Urea: Urea can be used to increase solute intake, which can help correct serum sodium levels in patients with euvolemic hyponatremia 5.
- Hypertonic Saline: Although 0.9% saline is not recommended for treating SIADH due to rapid fluctuations in serum sodium levels 5, hypertonic saline (3%) can be used in patients with severe symptoms, such as seizures or coma 7.
- Desmopressin: In some cases, desmopressin can be used to prevent overly rapid correction of serum sodium levels in high-risk patients 5.
Key Considerations
When treating euvolemic hyponatremia, it is essential to:
- Identify the underlying cause of hyponatremia, if possible 7, 6
- Monitor serum sodium levels closely to avoid overly rapid correction, which can lead to osmotic demyelination syndrome 7, 5
- Consider the patient's volume status and adjust treatment accordingly 7, 6
- Be aware of the potential side effects of treatment, such as those associated with VRAs 4