From the Guidelines
The workup for hyponatremia with low serum and urine osmolality should focus on diagnosing water intoxication or primary polydipsia, and management typically involves fluid restriction to 1-1.5 L/day, addressing underlying causes, and monitoring serum sodium, as recommended by recent guidelines 1. The diagnosis of hyponatremia with low serum and urine osmolality requires confirmation of true hyponatremia with serum sodium <135 mEq/L, low serum osmolality <280 mOsm/kg, and inappropriately dilute urine osmolality <100 mOsm/kg. Some key points to consider in the workup include:
- Obtaining a thorough history focusing on fluid intake, medications, psychiatric conditions, and symptoms
- Physical examination to assess volume status
- Laboratory tests, including serum electrolytes, BUN, creatinine, glucose, TSH, cortisol, and urine studies (sodium, osmolality, specific gravity)
- Consideration of a water loading test to evaluate the kidneys' ability to excrete free water In severe cases (sodium <120 mEq/L or neurological symptoms), more aggressive treatment with hypertonic saline may be necessary, but this should be done with caution and careful monitoring to avoid rapid correction and the risk of central pontine myelinolysis, as noted in recent guidelines 1. Key considerations in management include:
- Fluid restriction to 1-1.5 L/day
- Addressing underlying causes of hyponatremia
- Monitoring serum sodium levels closely
- Avoiding rapid correction of serum sodium to prevent central pontine myelinolysis, with a recommended increase of up to 5 mmol/L in the first hour and a limit of 8-10 mmol/L every 24 hours thereafter, 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 workup for hyponatremia and low serum and urine osmolality is not directly addressed in the provided drug label. However, the label does discuss the treatment of hyponatremia with tolvaptan.
- Key points:
- Tolvaptan is used to treat euvolemic or hypervolemic hyponatremia.
- The underlying causes of hyponatremia in the studies included heart failure, liver cirrhosis, SIADH, and others.
- Patients with acute and transient hyponatremia, primary polydipsia, uncontrolled adrenal insufficiency, or uncontrolled hypothyroidism were excluded from the studies.
- 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 2. However, the FDA drug label does not provide information on the workup for hyponatremia and low serum and urine osmolality.
From the Research
Evaluation of Hyponatremia
- Hyponatremia is defined as a serum sodium level of less than 135 mEq/L 3
- The evaluation of hyponatremia relies on clinical assessment and estimation of serum sodium, urine electrolytes, and serum and urine osmolality in addition to other case-specific laboratory parameters 4
- Measurement of the effective serum tonicity (serum osmolality less serum urea level) is the first step in the laboratory evaluation 5
Laboratory Diagnosis
- Serum osmolality less than 280 mOsm/kg indicates a hypo-osmolar state 5
- Urine osmolality is used to determine whether water excretion is normal or impaired 5
- A urine osmolality value of less than 100 mOsm/kg indicates complete and appropriate suppression of antidiuretic hormone secretion 5
- A urine sodium level less than 20 mmol/L is indicative of hypovolemia, whereas a level greater than 40 mmol/L is suggestive of the syndrome of inappropriate antidiuretic hormone secretion 5
Classification of Hyponatremia
- Hyponatremia can be classified into three categories based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia 3, 4
- Each category has different underlying causes and requires different management approaches 3, 4
Management 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, 6
- Hypertonic saline is reserved for patients with severely symptomatic hyponatremia 3