From the Guidelines
The management of hyponatremia should be tailored to its severity, onset, and underlying cause, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome and other complications, as recommended by the most recent and highest quality study 1.
Key Considerations
- For mild to moderate hyponatremia (sodium 125-135 mEq/L), fluid restriction to 800-1000 mL/day is often the first step, especially in cases of SIADH or hypervolemic states.
- For severe hyponatremia (sodium <125 mEq/L) with neurological symptoms, 3% hypertonic saline should be administered at 1-2 mL/kg/hour, with careful monitoring to avoid correcting sodium levels too rapidly (correction should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome).
- Specific treatments target underlying causes: diuretics like furosemide (20-40 mg IV/oral) for volume overload; vasopressin receptor antagonists such as tolvaptan (starting at 15 mg daily) for SIADH; hormone replacement for adrenal insufficiency; and discontinuation of offending medications.
Monitoring and Education
- Frequent monitoring of serum sodium (every 2-4 hours in severe cases) is essential during correction.
- Patients should be educated about appropriate fluid intake and, when indicated, sodium supplementation through diet or salt tablets.
Underlying Cause
- Addressing the underlying cause—whether heart failure, cirrhosis, kidney disease, endocrine disorders, or medication effects—is crucial for long-term management, as emphasized in the study 1.
Treatment Approach
- The treatment approach should prioritize the correction of serum sodium levels while minimizing the risk of complications, with a focus on individualized care based on the underlying cause and severity of hyponatremia, as recommended by the study 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 primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies.
The appropriate management for a patient with hyponatremia (low sodium levels) may include treatment with tolvaptan, a V2-receptor antagonist. Tolvaptan has been shown to be effective in increasing serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.
- Key considerations for the use of tolvaptan include:
- Monitoring of serum sodium levels to avoid hypernatremia
- Adjustment of fluid intake to prevent excessive free-water loss
- Potential interactions with other medications, such as CYP3A inhibitors and angiotensin receptor blockers
- Avoidance of concomitant use with V2-agonists, such as desmopressin 2.
From the Research
Management of Hyponatremia
The management of hyponatremia is based on the underlying cause and the patient's volume status, which can be categorized into hypovolemic, euvolemic, or hypervolemic hyponatremia 3, 4, 5.
- Hypovolemic hyponatremia is treated with normal saline infusions to correct the volume deficit.
- Euvolemic hyponatremia is treated by restricting free water consumption or using salt tablets or intravenous vaptans.
- Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and restricting free water intake.
Treatment Approaches
Treatment approaches for hyponatremia include:
- Fluid restriction for euvolemic patients
- Isotonic saline for hypovolemic patients
- Diuresis for hypervolemic patients
- Hypertonic saline for severely symptomatic patients
- Medications such as vaptans for euvolemic and hypervolemic hyponatremia 3, 4, 5
Severe Symptomatic Hyponatremia
Severely symptomatic hyponatremia is a medical emergency that requires immediate treatment with bolus hypertonic saline to increase the serum sodium level by 4-6 mEq/L within 1-2 hours, but not exceeding a correction limit of 10 mEq/L within the first 24 hours 3, 4.
Role of Vaptans
Vaptans, such as tolvaptan, can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but may have adverse effects such as overly rapid correction of hyponatremia and increased thirst 3, 6. A very low dose of tolvaptan (7.5 mg) may be effective with less risk of overcorrection compared to higher doses 6.
Clinical Practice Guidelines
Clinical practice guidelines for the diagnosis and treatment of hyponatremia have been developed by various societies, including the European Society of Intensive Care Medicine, the European Society of Endocrinology, and the European Renal Association-European Dialysis and Transplant Association 7. These guidelines aim to provide a common and holistic approach to the management of hyponatremia.