From the Guidelines
For patients with severe hyponatremia (sodium level less than 120 mEq/L), the management approach should prioritize careful correction to prevent neurological complications, with a focus on determining if the patient is symptomatic and addressing the underlying cause, as recommended by the most recent guidelines 1. The initial treatment should focus on determining the severity of symptoms and the underlying cause of hyponatremia.
- For symptomatic patients, administration of 3% hypertonic saline may be considered, as suggested by recent guidelines 1.
- The correction rate should not exceed 8 mEq/L per 24-hour period to avoid osmotic demyelination syndrome, as recommended by the American Association for the Study of Liver Diseases 1.
- For asymptomatic patients, fluid restriction (typically <1 L/day) is recommended, along with cessation of diuretics and consideration of albumin infusion for severe cases, as outlined in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. Key considerations in managing severe hyponatremia include:
- Frequent monitoring of serum sodium levels to ensure appropriate correction rates
- Careful assessment of volume status to guide therapy
- Consideration of vasopressin receptor antagonists for short-term use in specific cases, as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines 1
- Loop diuretics may be added when treating hypervolemic states, with careful monitoring to avoid overcorrection. The goal is to improve serum sodium levels while minimizing the risk of neurological complications, as emphasized by the most recent and highest quality studies 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. For patients with a serum sodium of <130 mEq/L or <125 mEq/L, the effects at Day 4 and Day 30 remained significant (see Table 2).
The management approach for a patient with severe hyponatremia (sodium level less than 120 mEq/L) may include the use of tolvaptan, as it has been shown to be effective in increasing serum sodium levels in patients with hyponatremia, including those with severe hyponatremia (serum sodium <125 mEq/L) 2.
- Key considerations:
- Tolvaptan is a selective V2 vasopressin receptor antagonist that increases serum sodium levels by increasing free-water excretion.
- The dose of tolvaptan can 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) is reached.
- Patients should be monitored to ensure serum sodium remains within normal limits, and management may include dose decreases or interruption of tolvaptan treatment if hypernatremia is observed.
- Serum potassium levels should be monitored during concomitant drug therapy with angiotensin receptor blockers, angiotensin converting enzyme inhibitors, and potassium-sparing diuretics.
- Important safety information:
- Concomitant use of tolvaptan with strong CYP3A inhibitors is contraindicated.
- Avoid co-administration of tolvaptan with moderate CYP3A inhibitors.
- Patients should avoid grapefruit juice beverages while taking tolvaptan.
- Avoid concomitant use of tolvaptan with strong CYP3A inducers.
- Tolvaptan may interfere with the V2-agonist activity of desmopressin (dDAVP), and concomitant use should be avoided.
From the Research
Management Approach for Severe Hyponatremia
The management approach for a patient with severe hyponatremia (sodium level less than 120 mEq/L) involves several key considerations:
- Classification of Hyponatremia: Hyponatremia can be classified based on the volume status of the patient as hypovolemic, euvolemic, or hypervolemic 3, 4, 5, 6.
- Symptom Severity: The severity of symptoms depends on the rapidity of development, duration, and severity of hyponatremia. Severe symptoms include delirium, confusion, impaired consciousness, ataxia, seizures, and brain herniation 3, 4, 5.
- Treatment Approach: The approach to managing hyponatremia should consist of treating the underlying cause. For severely symptomatic hyponatremia, bolus hypertonic saline can be used 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, 4.
- Correction Rate: The rate of correction is dependent upon the duration, degree of hyponatremia, and the presence or absence of symptoms. Excessive rapid correction should be avoided to prevent irreversible neurological complications, including central osmotic demyelination 3, 4, 6.
- Pharmacological Agents: Vaptans, orally taken vasopressin antagonists, have been shown to provide effective, specific, and safe therapy for hyponatremia, particularly in patients with euvolemic hyponatremia 5.
- Individualized Treatment: Each patient's treatment should be individualized based on their specific condition, with careful monitoring of sodium levels and adjustment of treatment as needed 7.
Key Considerations
Some key considerations in managing severe hyponatremia include:
- Identifying the Underlying Cause: Identifying the underlying cause of hyponatremia is crucial in guiding treatment 3, 4, 5, 6.
- Monitoring Sodium Levels: Close monitoring of sodium levels is essential to avoid excessive rapid correction and to adjust treatment as needed 3, 4, 6, 7.
- Avoiding Overly Rapid Correction: Avoiding overly rapid correction of sodium levels is critical to prevent irreversible neurological complications, including central osmotic demyelination 3, 4, 6.