What is the appropriate work-up for hyponatremia (low sodium levels)?

From the Guidelines

The workup for hyponatremia should begin with a thorough history, physical examination, and basic laboratory tests including serum sodium, osmolality, urine sodium, and urine osmolality. First, determine if the hyponatremia is hypotonic (most common), isotonic (pseudohyponatremia), or hypertonic (from hyperglycemia). For hypotonic hyponatremia, assess volume status as hypovolemic, euvolemic, or hypervolemic. Hypovolemic causes include GI losses, diuretics, and adrenal insufficiency. Euvolemic causes include SIADH, hypothyroidism, and medication effects. Hypervolemic causes include heart failure, cirrhosis, and nephrotic syndrome. Additional tests should include thyroid function tests, cortisol levels, and medication review. Urine sodium >20 mEq/L suggests renal sodium losses or SIADH, while <20 mEq/L suggests extrarenal losses or edematous disorders. Serum uric acid and BUN may help differentiate SIADH from other causes.

Key Considerations

• For severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms), consider 3% hypertonic saline at 100-150 mL over 10-20 minutes, which can be repeated, aiming for a sodium correction rate not exceeding 8-10 mEq/L in 24 hours to avoid osmotic demyelination syndrome, as recommended by the American Association for the Study of Liver Diseases 1.
• The use of vasopressin receptor antagonists in cirrhosis can raise serum sodium during treatment, but they should be used with caution only for a short term (≤30 days) 1.
• When correction of chronic hyponatremia is indicated in patients with cirrhosis, the goal rate of increase of serum (Na) is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period to ameliorate the risk of ODS 1.

Management Strategies

• Mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms does not require specific management apart from monitoring and water restriction 1.
• Water restriction to 1,000 mL/day and cessation of diuretics is recommended in the management of moderate hyponatremia (120-125 mEq/L), and a more severe restriction of water intake with albumin infusion is recommended for severe hyponatremia (<120 mEq/L) 1.
• Hypovolemic hyponatremia should be managed by discontinuation of diuretics and expansion of plasma volume with normal saline, as suggested by the guidelines on the management of ascites in cirrhosis 1. The underlying cause must be treated specifically once identified.

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.

The appropriate work-up for hyponatremia is not directly addressed in the provided drug label. Key points to consider in the work-up of hyponatremia include:

• Identifying the underlying cause of hyponatremia, such as heart failure, liver cirrhosis, or syndrome of inappropriate antidiuretic hormone (SIADH)
• Assessing the patient's volume status (euvolemic or hypervolemic)
• Evaluating the patient's symptoms and serum sodium levels However, the label does not provide a clear outline for the work-up of hyponatremia. 2

From the Research

Diagnosis of Hyponatremia

The diagnosis of hyponatremia involves several steps, including:

• Confirming true hypotonic hyponatremia 3
• Assessing the severity of hyponatremia symptoms 3
• Measuring urine osmolality 3
• Classifying hyponatremia based on the urine sodium concentration and extracellular fluid status 3, 4
• Ruling out any coexisting endocrine disorder and renal failure 3

Classification of Hyponatremia

Hyponatremia can be classified into several types, including:

• Hypovolemic hyponatremia, characterized by extracellular fluid volume deficit 4
• Hypervolemic hyponatremia, characterized by extracellular fluid volume expansion 4
• Euvolemic hyponatremia, characterized by normal extracellular fluid volume 4
• Isotonic hyponatremia, characterized by normal plasma osmolality 4
• Hypertonic hyponatremia, characterized by high plasma osmolality 4

Treatment of Hyponatremia

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

• Restricting free water and hypotonic fluid intake 4
• Using hypertonic saline to correct symptomatic hyponatremia 4, 5
• Using vasopressin antagonists to correct symptomatic hyponatremia 4
• Correcting hypokalemia 3
• Administering albumin and 3% saline in advanced liver disease 3
• Water restriction and/or the use of demeclocycline or lithium or furosemide and salt supplementation for chronic asymptomatic hyponatremia 6

Rate of Correction

The rate of correction of hyponatremia is crucial to prevent neurological complications, and should be:

• Rapid correction (1 mmol/l/hr increase rate of serum sodium) for acute severe hyponatremia (<48 hrs) 6
• Slow correction (0.5 mmol/l/hr or less) for chronic symptomatic hyponatremia 6, 4
• Avoiding excessive rapid correction to prevent osmotic demyelination syndrome 6, 4, 5