How do you correct reset osmostat (osmoregulation disorder) hyponatremia (low sodium levels)?

From the Guidelines

To correct reset osmostat hyponatremia, the primary approach is to treat the underlying condition causing the reset osmostat, as this form of hyponatremia is typically secondary to another disorder. Common causes include tuberculosis, malnutrition, psychogenic polydipsia, and certain malignancies. Unlike other forms of hyponatremia, fluid restriction is generally not effective for reset osmostat syndrome because the body maintains a new, lower setpoint for serum sodium. Patients typically maintain their sodium levels between 125-135 mEq/L despite changes in fluid intake. Management should focus on addressing the primary condition while ensuring adequate nutrition and avoiding excessive free water intake. In cases where the underlying cause cannot be corrected, the hyponatremia may persist but usually remains stable and asymptomatic. Sodium supplementation is rarely indicated unless levels fall below the reset range. The pathophysiology involves an abnormal setting of the osmostat that regulates ADH secretion, resulting in ADH release at lower serum osmolality thresholds than normal, but with preserved osmotic regulation within this new range.

Key Considerations

• The most recent and highest quality study on this topic is from 2021, which provides guidelines on the management of ascites in cirrhosis 1.
• According to these guidelines, fluid restriction to 1–1.5 L/day should be reserved for those who are clinically hypervolaemic with severe hyponatraemia (serum sodium <125 mmol/L) 1.
• Hypertonic sodium chloride (3%) administration may improve hyponatraemia, but it is best reserved for those with severely symptomatic acute hyponatraemia, especially if a transplant is imminent 1.
• The management of hypervolemic hyponatremia requires attainment of a negative water balance, and non-osmotic fluid restriction is helpful in preventing a further decrease in serum sodium levels, but it is seldom effective in improving natremia 1.

Treatment Approach

• Treating the underlying condition causing the reset osmostat is the primary approach.
• Ensuring adequate nutrition and avoiding excessive free water intake is crucial.
• Sodium supplementation is rarely indicated unless levels fall below the reset range.
• Hypertonic sodium chloride administration should be limited to severely symptomatic hyponatremia, and serum sodium concentration should not increase more than 8 mmol/L per day to avoid the risk of central pontine myelinolysis 1.

From the FDA Drug Label

In patients receiving tolvaptan tablets who develop too rapid a rise in serum sodium, discontinue or interrupt treatment with tolvaptan tablets and consider administration of hypotonic fluid. The correction of reset osmostat hyponatremia involves careful management to avoid too rapid correction of serum sodium, which can cause osmotic demyelination syndrome.

• The goal is to correct serum sodium at a rate of less than 12 mEq/L/24 hours.
• Tolvaptan can be used to treat hyponatremia, but it should be initiated and re-initiated in a hospital where serum sodium can be closely monitored.
• If too rapid a rise in serum sodium occurs, discontinue or interrupt treatment with tolvaptan and consider administration of hypotonic fluid 2.
• Fluid restriction during the first 24 hours of therapy with tolvaptan should generally be avoided to minimize the risk of overly rapid correction of serum sodium.
• Patients receiving diuretics should undergo close monitoring of serum sodium, as co-administration of diuretics increases the risk of too rapid correction of serum sodium 2.

From the Research

Correction of Reset Osmostat Hyponatremia

To correct reset osmostat hyponatremia, the following approaches can be considered:

• In the acute phase, hypertonic saline treatment may be used to improve symptoms and increase serum sodium concentration 3.
• In the chronic phase, water restriction can be implemented to further improve serum sodium levels 3.
• Vasopressin receptor antagonists (VRAs) have shown promise in treating euvolemic or hypervolemic hyponatremia, with significant increases in serum sodium concentration and response rate compared to placebo 4.
• VRAs can induce urinary dilution, leading to an increase in serum sodium concentration, and are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia 4, 5.

Diagnostic Considerations

• Preservation of urinary concentrating and diluting ability at a lower-than-normal serum sodium concentration is diagnostic of a reset osmostat 3, 6.
• A thorough workup is necessary to identify the cause of hyponatremia, and a systematic and logical approach is needed to diagnose reset osmostat 7.
• Early recognition of a reset osmostat can avoid the need to normalize serum sodium concentration, expedite hospital discharge, and limit potential harm from overcorrecting acute hyponatremia 3.

Treatment Implications

• The presence of a reset osmostat often confounds the treatment of concomitant acute hyponatremia, and treatment should be tailored to the individual patient's needs 3, 7.
• While traditional managements such as fluid restriction and hypertonic saline may be difficult to maintain or ineffective, VRAs offer a promising alternative for the treatment of euvolemic or hypervolemic hyponatremia 4, 5.