Evaluation
Volume status should be assessed to help determine the underlying cause. If hyperglycemia is present, the serum sodium concentration should be corrected for the effect of glucose to exclude hypertonic hyponatremia.
Principles of Therapy
General Measures
General measures in the management of hyponatremia include treating the underlying cause and identifying any drugs that may contribute to the condition. Once a causative medication is identified, it should be discontinued unless there is no reasonable alternative or stopping the medication would cause more harm to the patient. Management should also focus on decreasing the intake of electrolyte-free water by imposing fluid restriction, eliminating intravenous hypotonic fluids, and increasing dietary salt intake.
Hospital Admission
Hospital admission is required for acute and severe hyponatremia with an onset of <48 hours, serum sodium concentration <120 mEq/L, and symptoms of altered mental states and seizures. Fluid restriction is the mainstay of treatment, but one may also consider hypertonic saline solution and admission to the intensive care unit.
Treatment Goals for Hospitalized Patients
The treatment goals for hospitalized patients with hyponatremia are to prevent further decline in the serum sodium concentration, decrease intracranial pressure in patients at risk of developing brain herniation, and relieve the symptoms of hyponatremia.
Rapid correction of hyponatremia should be avoided, particularly in patients with chronic hyponatremia, to prevent the development of osmotic demyelination syndrome (ODS). The goal of initial therapy is to raise serum sodium concentration by 4-6 mEq/L during the first 24 hours. Rechecking of serum sodium concentration can be done 1 hour after the initial administration of hypertonic saline and every 6 hours after in order to adjust the interval and infusion rate of hypertonic saline. The rate of sodium correction can be reevaluated if there is improvement of symptoms or if the serum sodium concentration increases by 5-9 mEq/L. An increase in serum sodium should not exceed 10-12 mEq/L in 24 hours or 18 mEq/L in 48 hours for patients at intermediate risk of ODS. A minimum correction should be 4-8 mEq/L. The maximum correction should be 8 mEq/L with a minimum correction of 4-6 mEq/L in any 24-hour period for patients at high risk of ODS.
Nonpharmacological
Hypovolemic Hyponatremia
Hyponatremia_Management 1
The goal is to correct plasma sodium and restore intravascular volume. Most cases respond to intravenous (IV) infusion of isotonic (0.9%) saline solution or Ringer’s lactate solution for volume repletion. Treatment also involves occasional use of salt tablets and treating the underlying cause. Diuretic therapy should be discontinued. During treatment, it is necessary to monitor urine output because output of >100 mL/hr can be a warning sign of overcorrection.
Euvolemic Hyponatremia
Euvolemic hyponatremia should be treated with fluid restriction and correction of the underlying cause. Fluid restriction should be limited to 500 mL less than the daily urinary volume. Salt and protein should not be restricted. Sodium levels in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) will decrease further with IV fluid administration.
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
In all cases of SIADH, fluid restriction is the first line of treatment. For asymptomatic hyponatremia that persisted >48 hours, initial fluid restriction could start at 800-1,200 mL/24 hr and be subsequently titrated to 500 mL below the daily urine output volume.
Hypervolemic Hyponatremia
Hypervolemic hyponatremia should be treated with sodium and fluid restriction (approximately <800-1,000 mL/24 hr), diuresis, and correction of the underlying cause.
Pharmacological therapy
Hyponatremia_Management 2Salt Tablets
Salt tablets can be a treatment in addition to fluid restriction in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) with very mild or absent symptoms and a serum sodium >120 mEq/L. This can be a substitute for hypertonic saline in non-emergency situations. Salt tablets may be effective in hypovolemic patients who are treated as outpatients together with the reversal of the cause of hypovolemia. This should not be given to edematous patients (eg patients with heart failure or cirrhosis).
Urea
Oral or enteral (via a gastric tube) administration of Urea increases the serum sodium concentration by increasing the excretion of electrolyte-free water. This is an alternative to the combination of loop diuretics and oral salt tablets. Urea may be considered in patients with euvolemic or hypervolemic hyponatremia with mild to moderate symptoms. In patients with SIADH, there were reported favorable short- and long-term outcomes with urea therapy for hyponatremia.
Vasopressin Receptor Antagonists (Vaptans)
Example drugs: Conivaptan, Tolvaptan
Vasopressin reception antagonists are an alternative or possible addition to fluid restriction and sodium chloride administration in patients with hyponatremia. These are approved for the treatment of hospitalized patients with severe hypervolemic and euvolemic hyponatremia. The 2014 ESICM-ESE-ERA guideline does not recommend the use of vaptans in moderate hyponatremia due to increased risk of overcorrection, osmotic demyelination syndrome (ODS), and hepatotoxicity. These are not indicated for the treatment of hypovolemic hyponatremia. Vasopressin reception antagonists produce a selective water diuresis (also called aquaresis) without affecting sodium and potassium excretion. The ensuing loss of water will tend to correct the hyponatremia. Several clinical trials have shown that vaptans can increase sodium levels in patients with cirrhosis and heart failure.
Conivaptan
Conivaptan is an intravenous combined V1a and V2 receptor antagonist approved for the short-term treatment of euvolemic and hypervolemic hyponatremia.
Tolvaptan
Tolvaptan is an oral selective nonpeptide V2 receptor antagonist approved for the treatment of euvolemic and hypervolemic hyponatremia in the United States, while in the European Union, it is only approved for the treatment of euvolemic hyponatremia. It was shown in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan that patients with hyponatremia and heart failure who received Tolvaptan had an associated reduction in cardiovascular morbidity and mortality, although there were several confounding variables, and further study is needed. The Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT) trials demonstrated increased sodium levels with Tolvaptan in patients with SIADH, cirrhosis, and heart failure. Tolvaptan should not be used for longer than 30 days or in patients with hepatic impairment, as it may worsen liver function.