From the Guidelines
Refractory hyponatremia should be treated with a combination of fluid restriction and pharmacological therapy, prioritizing correction rates not exceeding 8 mmol/L per day to avoid central pontine myelinolysis, as recommended by the most recent guidelines 1.
Treatment Approach
The treatment approach for refractory hyponatremia depends on the underlying cause, which can be hypovolemic, hypervolemic, or euvolemic.
- For hypovolemic hyponatremia, isotonic saline infusion is recommended to expand plasma volume and correct the causative factor 1.
- For hypervolemic hyponatremia, attainment of a negative water balance is crucial, which can be achieved through non-osmotic fluid restriction and, in some cases, the use of hypertonic sodium chloride administration, but with caution to avoid worsening volume overload and ascites 1.
- For patients with severe hyponatremia who are expected to undergo liver transplant, hypertonic sodium chloride administration can be considered, but with careful monitoring to avoid rapid correction of serum sodium levels 1.
Pharmacological Therapy
Pharmacological therapy may include the use of vasopressin receptor antagonists (vaptans) like tolvaptan, which can be effective in treating SIADH-related refractory hyponatremia, as suggested by earlier guidelines 1. However, the most recent and highest quality evidence prioritizes the management strategies outlined in the 2018 EASL clinical practice guidelines 1.
Monitoring and Correction Rates
Frequent monitoring of serum sodium levels is essential, especially during the initial phases of treatment, to avoid rapid correction and prevent complications like osmotic demyelination syndrome 1. The correction rate should not exceed 8 mmol/L per day, with an initial rapid correction aimed at alleviating clinical symptoms, followed by a more gradual increase in serum sodium concentration 1.
Underlying Cause
Addressing the underlying cause of hyponatremia is crucial for effective management, as persistent triggers can make treatment challenging regardless of symptomatic relief 1.
From the FDA Drug Label
In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. The dose of tolvaptan could be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) was reached
The treatment for refractory hyponatremia is tolvaptan, which can be administered orally at an initial dose of 15 mg once daily, with possible increases to 30 mg once daily and then to 60 mg once daily until normonatremia is reached or the maximum dose is achieved 2.
- Key points:
- Tolvaptan is effective in increasing serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.
- The dose of tolvaptan can be titrated to achieve the desired effect.
- Tolvaptan has been shown to be effective in patients with various underlying causes of hyponatremia, including heart failure, liver cirrhosis, and SIADH.
From the Research
Treatment Options for Refractory Hyponatremia
The treatment for refractory hyponatremia, a condition characterized by low sodium levels in the blood, depends on the underlying cause and the severity of the symptoms.
- For patients with severely symptomatic hyponatremia, bolus hypertonic saline is recommended to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours, but by no more than 10 mEq/L within the first 24 hours 3.
- Vasopressin receptor antagonists (Vaptans) can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects such as poor palatability and gastric intolerance with urea, and overly rapid correction of hyponatremia and increased thirst with vaptans 3, 4, 5.
- Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is an oral agent approved for raising sodium levels in hypervolemic and euvolemic hyponatremia, and has been shown to be safe and effective in long-term treatment 6.
- Urea can be used as a safe and effective treatment for fluid restriction-refractory hyponatraemia, with a recommended starting dose of ≥30 g/d, in patients with SIADH and moderate to profound hyponatraemia who are unable to undergo, or have failed fluid restriction 7.
Considerations for Treatment
When evaluating patients with hyponatremia, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3.