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

From the Guidelines

The workup for hyponatremia should begin with a thorough history and physical examination, followed by laboratory testing to determine the cause, with a focus on assessing volume status and correcting serum sodium levels gradually to avoid osmotic demyelination syndrome, as recommended by the most recent guidelines 1. The initial steps in the workup of hyponatremia include:

• Laboratory testing to determine the cause, including serum sodium, potassium, glucose, blood urea nitrogen, creatinine, and osmolality, along with urine sodium and osmolality
• Assessment of volume status, categorizing patients as hypovolemic, euvolemic, or hypervolemic
• For hypovolemic hyponatremia, fluid resuscitation with isotonic saline is appropriate
• In euvolemic hyponatremia, fluid restriction to 800-1000 mL/day is often recommended
• Hypervolemic states require both sodium and fluid restriction along with diuretics like furosemide 20-40 mg daily Severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms) requires more aggressive treatment with hypertonic (3%) saline, aiming for a correction rate of 4-6 mEq/L in the first 24 hours to avoid osmotic demyelination syndrome, as suggested by recent practice guidance 1. Specific causes of hyponatremia require targeted therapy, such as:
• SIADH, which may need vasopressin receptor antagonists like tolvaptan starting at 15 mg daily
• Adrenal insufficiency, which requires hydrocortisone replacement Medication review is essential, as many drugs, including thiazide diuretics, SSRIs, and certain antiepileptics, can cause hyponatremia and may need to be discontinued or adjusted, as noted in the EASL clinical practice guidelines 1. It is crucial to correct serum sodium levels gradually to avoid osmotic demyelination syndrome, with a goal rate of increase of 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, as recommended by the American Association for the Study of Liver Diseases 1.

From the FDA Drug Label

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. Symptomatic patients, patients likely to require saline therapy during the course of therapy, patients with acute and transient hyponatremia associated with head trauma or postoperative state and patients with hyponatremia due to primary polydipsia, uncontrolled adrenal insufficiency or uncontrolled hypothyroidism were excluded 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 work up for hyponatremia is not directly addressed in the provided drug label. However, it can be inferred that the diagnosis and treatment of hyponatremia involve:

• Assessing serum sodium concentrations: Measuring serum sodium levels to determine the severity of hyponatremia.
• Identifying underlying causes: Ruling out conditions such as primary polydipsia, uncontrolled adrenal insufficiency, or uncontrolled hypothyroidism.
• Avoiding fluid restriction: Initially, to prevent overly rapid correction of serum sodium.
• Monitoring and adjusting treatment: As necessary, to achieve normonatremia (serum sodium >135 mEq/L) 2.

From the Research

Diagnostic Approach to Hyponatremia

The diagnostic approach to hyponatremia involves several steps, including:

• Measurement of serum sodium level and osmolality to confirm the diagnosis of hyponatremia 3, 4, 5
• Assessment of extracellular volume status on physical examination to categorize patients as hypovolemic, euvolemic, or hypervolemic hyponatremia 3, 4
• Measurement of effective serum tonicity (serum osmolality less serum urea level) to determine the underlying cause of hyponatremia 4
• Urine osmolality and sodium levels to determine whether water excretion is normal or impaired 4, 6
• Hormone levels (thyroid-stimulating hormone and cortisol) and arterial blood gases should be determined in difficult cases of hyponatremia 4

Treatment of Hyponatremia

The treatment of hyponatremia depends on the underlying cause and severity of symptoms, and may include:

• Treating the underlying cause of hyponatremia, such as correcting hypovolemia or treating heart failure 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
• Hypertonic saline is reserved for patients with severely symptomatic hyponatremia, and should be used with caution to avoid overly rapid correction of serum sodium levels 3, 6, 5
• Free water restriction combined with increased solute intake (e.g., urea) is the most effective therapy to treat patients with SIADH 6

Special Considerations

• Acute hyponatremia is a medical emergency and requires prompt treatment to prevent severe neurological symptoms and osmotic demyelination syndrome (ODS) 6
• Chronic hyponatremia requires careful management to avoid overly rapid correction of serum sodium levels, which can cause ODS 3, 6
• Patients with profound hyponatremia require a complete minimum diagnostic workup, including measurement of serum sodium and osmolality, urine osmolality and sodium levels, and clinical evaluation of volume status 7