From the Guidelines
Hyponatremia is classified into three main categories based on volume status: hypovolemic, euvolemic, and hypervolemic hyponatremia, and the initial step in management should include confirming true hyponatremia and assessing volume status. The classification of hyponatremia is crucial in determining the underlying cause and guiding the workup and treatment. Hypovolemic hyponatremia occurs due to sodium and water loss with greater sodium than water loss, with causes including vomiting, diarrhea, diuretic use, adrenal insufficiency, and third-spacing, as noted in the management of ascites in cirrhosis guidelines 1. The workup for hypovolemic hyponatremia should include assessment of volume status, urine sodium, and adrenal function tests.
Euvolemic hyponatremia presents with normal volume status and is commonly caused by SIADH, hypothyroidism, psychogenic polydipsia, and certain medications. Workup should include thyroid function tests, medication review, and evaluation for SIADH with urine osmolality and sodium measurements. Hypervolemic hyponatremia occurs with excess total body water and sodium, with relatively more water retention, seen in conditions like heart failure, cirrhosis, and nephrotic syndrome. The management of hyponatremia in cirrhosis has been outlined in guidelines, including the use of vaptans, such as tolvaptan, which has been shown to be effective in improving serum sodium concentration in patients with hypervolemic hyponatremia 2.
The initial steps in any hyponatremia workup should include:
- Confirming true hyponatremia (not pseudohyponatremia)
- Measuring serum osmolality to distinguish between hypotonic, isotonic, and hypertonic hyponatremia
- Assessing volume status through physical examination and history
- Checking urine sodium and osmolality Additional tests may include thyroid and adrenal function tests, brain imaging if neurological symptoms are present, and medication review. Understanding the underlying pathophysiology is crucial as treatment differs significantly based on the cause, with inappropriate management potentially leading to serious complications like osmotic demyelination syndrome. The treatment of hypervolemic hyponatremia should focus on inducing a negative water balance, and vaptans, such as tolvaptan, may be considered in patients with severe hyponatremia 2.
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 classes of hyponatremia mentioned in the label are:
- Euvolemic hyponatremia: caused by syndrome of inappropriate antidiuretic hormone (SIADH) and others
- Hypervolemic hyponatremia: caused by heart failure and liver cirrhosis
The causes of hyponatremia mentioned in the label are:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Others (not specified)
The next steps in work up are not explicitly mentioned in the label, but it can be inferred that:
- Patients with hyponatremia should be evaluated to determine the underlying cause of their condition
- Patients with euvolemic or hypervolemic hyponatremia may be treated with tolvaptan, with careful monitoring of serum sodium concentrations and neurologic status, especially during initiation and after titration [3] [4] 5
From the Research
Classes of Hyponatremia
- Hypovolemic hyponatremia: characterized by low blood volume, often due to dehydration or blood loss 6, 7
- Euvolemic hyponatremia: characterized by normal blood volume, often due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or other endocrinopathies 6, 8, 7
- Hypervolemic hyponatremia: characterized by high blood volume, often due to heart failure, nephrotic syndrome, or cirrhosis 6, 7
Causes of Hyponatremia
- Water retention due to elevated serum vasopressin levels or excessive fluid intake 6, 9
- Defective water excretion due to renal or adrenal insufficiency 9, 8
- Salt loss due to gastrointestinal, renal, cutaneous, or cerebral origin 8, 7
- Hyperglycemia or hypertriglyceridemia leading to hyper- or normoosmolar hyponatremia 8
Next Steps in Workup
- Evaluate fluid volume status to categorize patients as hypovolemic, euvolemic, or hypervolemic 6, 7
- Measure plasma osmolality, glucose, lipids, and proteins to differentiate between hypervasopressinemic and non-hypervasopressinemic hyponatremias 7
- Determine urine osmolality and sodium concentration to further diagnose the cause of hyponatremia 7
- Assess for underlying conditions such as heart failure, nephrotic syndrome, or cirrhosis in hypervolemic hyponatremia 6, 7
- Consider the use of arginine vasopressin receptor antagonists for treatment of euvolemic and hypervolemic hyponatremia 10