What are the treatments for chronic hyponatremia (low sodium levels in the blood)?

From the Guidelines

The treatment of chronic hyponatremia should be tailored to the underlying cause, with fluid restriction and pharmacological options like vasopressin receptor antagonists being considered, while ensuring correction rates do not exceed 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome, as recommended by the most recent guidelines 1.

Key Considerations

• The management of hyponatremia depends on its type, with hypovolemic hyponatremia requiring fluid resuscitation and hypervolemic hyponatremia necessitating a negative water balance 1.
• For hypervolemic hyponatremia, fluid restriction to 1-1.5 liters per day can be beneficial, although its effectiveness in improving serum sodium levels is limited 1.
• Vasopressin receptor antagonists, such as tolvaptan, can be effective in improving serum sodium levels, especially in conditions associated with high vasopressin levels like SIADH, heart failure, or cirrhosis 1.

Treatment Options

• Fluid restriction: 1-1.5 liters per day, particularly for asymptomatic chronic hyponatremia or in cases of SIADH or heart failure.
• Vasopressin receptor antagonists: tolvaptan, starting at 15 mg daily and titrating up to 60 mg daily based on serum sodium response.
• Loop diuretics: furosemide, 20-40 mg daily, may be beneficial in volume-overloaded states.
• Urea: 15-60 g daily dissolved in water, can be effective for SIADH when other treatments fail.

Monitoring and Precautions

• Regular monitoring of serum sodium levels (every 4-6 hours initially) is crucial during treatment.
• Correction rates should not exceed 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome.
• Addressing the underlying cause, such as discontinuing offending medications or treating malignancies, is fundamental to successful management.
• Dietary sodium supplementation may be appropriate in salt-wasting conditions, while protein restriction might benefit patients with cirrhosis.

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)

Tolvaptan is a treatment option for chronic hyponatremia, specifically for patients with:

• Hypervolemic hyponatremia
• Euvolemic hyponatremia
• Heart failure
• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) The usual starting dose for tolvaptan tablets is 15 mg administered once daily, which can be increased to a maximum of 60 mg once daily as needed to achieve the desired level of serum sodium. It is essential to initiate and re-initiate tolvaptan in a hospital setting, where serum sodium can be closely monitored, to avoid overly rapid correction of serum sodium, which can cause osmotic demyelination syndrome. Tolvaptan has been shown to cause a statistically significant increase in serum sodium levels compared to placebo in clinical studies 2, 2, and 2.

From the Research

Treatment Approaches for Chronic Hyponatremia

• The treatment of chronic hyponatremia should focus on addressing the underlying cause of the condition, with consideration of the patient's fluid volume status (hypovolemic, euvolemic, or hypervolemic hyponatremia) 3.
• For patients with euvolemic or hypervolemic hyponatremia, vasopressin receptor antagonists (vaptans) can be an effective treatment option, although their use is not without potential adverse effects, such as overly rapid correction of hyponatremia and increased thirst 3, 4.
• Urea can also be used to treat the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but it may have poor palatability and gastric intolerance 3.
• Hypertonic saline is typically reserved for patients with severely symptomatic hyponatremia, as it can rapidly increase serum sodium levels and reverse hyponatremic encephalopathy, but it must be used cautiously to avoid overly rapid correction 3, 5, 6.

Considerations for Treatment

• The correction of chronic hyponatremia must be done carefully to avoid osmotic demyelination, a rare but severe neurological condition that can result from overly rapid correction 3, 5, 6.
• The treatment approach should be individualized based on the severity of symptoms, the underlying cause of hyponatremia, and the patient's fluid volume status 3, 4, 6.
• Vasopressin receptor antagonists have shown promise in the treatment of hyponatremia, but their optimal indications and potential complications must be carefully considered 4, 7.

Management of Severe Hyponatremia

• Severely symptomatic hyponatremia is a medical emergency that requires immediate treatment with hypertonic saline to reverse cerebral edema and prevent brain herniation 3, 6.
• The goal of treatment is to increase serum sodium levels by 4-6 mEq/L within 1-2 hours, but not to exceed a correction limit of 10 mEq/L within the first 24 hours 3, 6.