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

From the Guidelines

The workup for hyponatremia should begin with a thorough history, physical examination, and basic laboratory tests to determine the cause and guide treatment, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome, as recommended by the most recent guidelines 1. The initial evaluation should include assessment of volume status, categorizing the patient as hypovolemic, euvolemic, or hypervolemic, which will guide the treatment approach.

• For hypovolemic hyponatremia, fluid resuscitation with normal saline is appropriate.
• Euvolemic hyponatremia often indicates SIADH and may require fluid restriction to 800-1000 mL/day, with consideration of salt tablets, urea (15-30 g/day), or vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) in resistant cases.
• Hypervolemic hyponatremia typically requires treatment of the underlying condition (heart failure, cirrhosis, nephrotic syndrome) along with fluid restriction and diuretics. The rate of sodium correction should not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, with slower correction (4-6 mEq/L/24h) for chronic hyponatremia, as recommended by the American Association for the Study of Liver Diseases 1. Severe symptomatic hyponatremia (seizures, coma) may require 3% hypertonic saline (100 mL over 10-15 minutes, repeatable up to 3 times) to raise sodium by 4-6 mEq/L acutely, while mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms does not require specific management apart from monitoring and water restriction 1. Identifying and addressing medication causes (thiazide diuretics, SSRIs, carbamazepine) and underlying conditions (adrenal insufficiency, hypothyroidism) is essential for comprehensive management, and the use of vasopressin receptor antagonists in cirrhosis can raise serum sodium during treatment, but should be used with caution only for a short term (≤30 days) 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

The appropriate workup for hyponatremia is not directly stated in the provided drug label. However, it can be inferred that the following conditions should be considered and possibly ruled out:

• Primary polydipsia
• Uncontrolled adrenal insufficiency
• Uncontrolled hypothyroidism
• Acute and transient hyponatremia associated with head trauma or postoperative state 2

From the Research

Diagnosis of Hyponatremia

• Hyponatremia is defined as a serum sodium level of less than 135 mEq/L 3
• The diagnosis of hyponatremia involves evaluating the patient's fluid volume status, which can be categorized into hypovolemic, euvolemic, or hypervolemic hyponatremia 3, 4, 5
• Plasma osmolality, glucose, lipids, and proteins should be measured to differentiate between hypervasopressinemic and non-hypervasopressinemic hyponatremias 4
• Urine osmolality, clinical assessment of extracellular fluid volume status, and urine sodium concentration provide important information for further differential diagnosis of hyponatremia 4

Treatment of Hyponatremia

• The approach to managing hyponatremia should consist of treating the underlying cause 3
• For most patients, treatment involves fluid restriction, isotonic saline, or diuresis, depending on the volume status 5, 6
• Hypertonic saline is used to treat severe symptomatic hyponatremia, with the goal of increasing the serum sodium level by 4-6 mEq/L within 1-2 hours, but not exceeding a correction limit of 10 mEq/L within the first 24 hours 3, 7, 5
• Vasopressin receptor antagonists, such as vaptans, may be effective in managing euvolemic and hypervolemic hyponatremia 3, 4, 6
• The rate of correction is dependent on the duration, degree of hyponatremia, and the presence or absence of symptoms, with excessive rapid correction avoided to prevent irreversible neurological complications 3, 4, 7, 5

Classification of Hyponatremia

• Hyponatremia can be classified according to the measured plasma osmolality as isotonic, hypertonic, or hypotonic 5
• Hypotonic hyponatremia is further classified according to the volume status of the patient as hypovolemic, hypervolemic, or euvolemic 5
• The syndrome of inappropriate antidiuretic hormone (SIADH) should be suspected in any patient with euvolemic hyponatremia with a urine osmolality above 100 mOsm/kg and urine sodium concentration above 40 mEq/l 4, 5