What is the protocol for managing hyponatremia (low sodium levels)?

From the Guidelines

The management of hyponatremia should prioritize correction of the underlying cause, with fluid restriction and pharmacological interventions tailored to the severity and onset of the condition, as recommended by the most recent guidelines 1.

Key Considerations

• For acute symptomatic hyponatremia, especially with neurological symptoms, administer 3% hypertonic saline at 100-150 mL over 10-20 minutes, which can be repeated 2-3 times until symptoms improve, with careful monitoring to prevent over-correction 1.
• The correction rate should not exceed 8-10 mEq/L in the first 24 hours and 18 mEq/L in 48 hours to prevent osmotic demyelination syndrome, as emphasized in recent practice guidance 1.
• For chronic hyponatremia, fluid restriction to 800-1000 mL/day is recommended for SIADH, with pharmacological options including oral salt tablets, loop diuretics like furosemide, and vasopressin receptor antagonists such as tolvaptan, starting at 15 mg daily 1.
• Underlying causes must be addressed, including discontinuation of offending medications, treatment of infections, or management of endocrine disorders, to ensure effective correction of hyponatremia 1.

Management Strategies

• Hypovolemic hyponatremia requires plasma volume expansion with saline solution and correction of the causative factor, such as excessive diuretic administration 1.
• Hypervolemic hyponatremia management aims to induce a negative water balance, with fluid restriction and pharmacological interventions as needed, while avoiding over-correction and its associated risks 1.
• Vasopressin receptor antagonists, such as tolvaptan, can be effective in improving serum sodium concentration, but should be used with caution and close monitoring, especially in patients with advanced cirrhosis 1.

Monitoring and Adjustment

• Regular monitoring of serum sodium every 2-4 hours during correction is essential, with adjustment of therapy based on response, to prevent both under-correction and over-correction 1.
• The goal rate of increase of serum sodium is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, to ameliorate the risk of osmotic demyelination syndrome, as recommended by recent guidelines 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 hyponatremia protocol involves the use of tolvaptan to increase serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.

• The initial dose of tolvaptan is 15 mg once daily, which can be increased 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) is reached.
• Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
• Patients should be monitored to ensure serum sodium remains within normal limits, and hypernatremia should be managed by dose decreases or interruption of tolvaptan treatment, combined with modification of free-water intake or infusion 2.

From the Research

Hyponatremia Protocol

• Hyponatremia is defined as a serum sodium level of less than 135 mEq/L and is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3.
• The approach to managing hyponatremia should consist of treating the underlying cause, and patients should be categorized according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3, 4.
• Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma), and symptom severity depends on the rapidity of development, duration, and severity of hyponatremia 3, 4, 5.
• Treatment options for hyponatremia include:
  • Fluid restriction
  • Hypertonic saline
  • Urea
  • Vaptans (vasopressin receptor antagonists)
  • Demeclocycline
  • Loop diuretics 3, 4, 6, 7
• For 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, 7.
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death 3, 6.
• The risk of overcorrection in rapid intermittent bolus vs slow continuous infusion therapies of hypertonic saline for patients with symptomatic hyponatremia has been studied, and both therapies were found to be effective and safe, with no difference in the overcorrection risk 7.