What is the appropriate treatment and workup for hyponatremia (low sodium levels)?

From the Guidelines

The treatment of hyponatremia should prioritize correcting the underlying cause, with severe cases requiring aggressive intervention, and the use of 3% hypertonic saline reserved for severely symptomatic patients, aiming for a sodium correction rate not exceeding 8-10 mEq/L in the first 24 hours, as recommended by the most recent guidelines 1.

Initial Workup

The initial workup for hyponatremia should include:

• Serum and urine osmolality
• Urine sodium
• Assessment of volume status to determine if the patient is hypovolemic, euvolemic, or hypervolemic

Treatment Approach

The treatment approach for hyponatremia depends on its severity, onset, and underlying cause. For mild to moderate hyponatremia (sodium >125 mEq/L), addressing the underlying cause is often sufficient. For severe hyponatremia (<125 mEq/L) or symptomatic cases with neurological manifestations, more aggressive intervention is needed.

Volume Status-Based Treatment

• Hypovolemic hyponatremia: isotonic saline (0.9% NaCl) at 100-200 mL/hour is appropriate to restore volume 1
• Euvolemic hyponatremia: fluid restriction to 800-1000 mL/day, and in cases of SIADH, salt tablets (1-2 g three times daily) or urea (15-30 g daily) may be used
• Hypervolemic hyponatremia: fluid restriction and diuretics like furosemide (20-40 mg IV or oral) are typically required

Severe Symptomatic Hyponatremia

For severe symptomatic hyponatremia, 3% hypertonic saline can be administered at 1-2 mL/kg/hour, aiming for a sodium correction rate not exceeding 8-10 mEq/L in the first 24 hours and 18 mEq/L in 48 hours to prevent osmotic demyelination syndrome, as recommended by recent guidelines 1.

Monitoring and Prevention of Complications

Throughout treatment, frequent monitoring of serum sodium (every 2-4 hours initially for severe cases) is essential to ensure appropriate correction rates and prevent complications, such as osmotic demyelination syndrome 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 Fluid restriction was to be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium, and during the first 24 hours of therapy 87% of patients had no fluid restriction.

The treatment for hyponatremia involves the use of tolvaptan, with an initial oral dose of 15 mg once daily, which can be increased to 30 mg and then 60 mg as needed, until normonatremia is reached.

• Key points:
  • Avoid fluid restriction during the first 24 hours of therapy to prevent overly rapid correction of serum sodium.
  • Tolvaptan can be effective in increasing serum sodium concentrations in patients with hyponatremia.
  • The percentage of patients requiring fluid restriction is significantly less in the tolvaptan-treated group compared to the placebo-treated group. 2

From the Research

Treatment of Hyponatremia

• The approach to managing hyponatremia should consist of treating the underlying cause 3
• Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 3
• Severely symptomatic hyponatremia is a medical emergency and should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 4, 5
• The treatment of hyponatremia depends on the presence and severity of symptoms, as well as the patient's volume status and the duration of hyponatremia 4, 5, 6

Diagnostic Approach

• Hyponatremia should be categorized according to the patient's fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3
• A physiological approach should be used to determine if hyponatremia is hypotonic, if it is mediated by arginine vasopressin, and if arginine vasopressin secretion is physiologically appropriate 4
• The diagnostic approach should consider the patient's volume status, the presence or absence of symptoms, duration of hypo-osmolality, and the presence or absence of risk factors for the development of neurologic complication 5

Management Strategies

• Clinical practice guidelines have been developed to provide a common and holistic view of the diagnosis and treatment of hyponatremia 6
• Vasopressin-2 receptor antagonists (vaptans) provide a new approach to the treatment of hyponatremia 7
• The use of vasopressin receptor antagonists in the management of hyponatremia should be based on their pharmacology, mechanism of action, and available efficacy data from clinical trials 7
• Optimal therapy of hyponatremia must consider balancing the risks of hyponatremia against the risks of correction for each patient individually 5