Hyponatremia Treatment

• Hospital admission is required for acute and severe hyponatremia with an onset of <48 hours, serum sodium concentration <120 mEq/L and with symptoms of altered mental state and seizures
  
  • Fluid restriction is the mainstay of treatment, but may also consider hypertonic saline solution and admission to intensive care unit

Treatment Goals for Hospitalized Patients

• Prevent further decline in the concentration of serum sodium
• Decrease intracranial pressure in patients at risk of developing brain herniation
• Relieve symptoms of hyponatremia
• Avoid rapid correction of hyponatremia to prevent osmotic demyelination syndrome (ODS) in patients with chronic hyponatremia
  
  • The goal of initial therapy is to raise serum sodium concentration by 4-6 mEq/L in a 24-hour period
    • 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
    • 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
  • 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
  • The maximum correction should be 8 mEq/L in any 24-hour period for patients at high risk of ODS

Hypovolemic Hyponatremia

• 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 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

• Treated with fluid restriction and correction of 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 SIADH will decrease further with IV fluid administration

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

• In all cases, fluid restriction is the first line of treatment
• For asymptomatic hyponatremia that persisted >48 hours, initial fluid restriction could start at 800-1200 mL/24 hr and be subsequently titrated to 500 mL below the daily urine output volume

Hypervolemic Hyponatremia

• Treated with sodium and fluid restriction (approximately <800-1000 mL/24 hr), diuresis and correction of underlying cause

General Measures

• Treat underlying cause
• Identify drugs that have been taken that can contribute to hyponatremia
  
  • Once identified, discontinue the drug unless there is no other reasonable substitute or stopping the medication can cause more harm to the patient

• Decrease intake of electrolyte-free water
  
  • Impose fluid restriction
  • Eliminate IV hypotonic fluids
  • Increase dietary salt

Salt Tablets

• Can be a treatment in addition to fluid restriction in patients with SIADH with very mild or absent symptoms and a serum sodium >120 mEq/L
• Can be a substitute for hypertonic saline in non-emergency situations
• May be effective in hypovolemic patients who are treated as outpatients together with the reversal of the cause of hypovolemia
• Should not be given to edematous patients

Urea

• Oral or enteral (via a gastric tube) administration of Urea increases the serum sodium concentration by increasing the excretion of electrolyte-free water
• It is an alternative to the combination of loop diuretics and oral salt tablets
• 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)

• Eg Conivaptan, Tolvaptan
• An alternative or possible addition to fluid restriction and sodium chloride administration in patients with hyponatremia
• 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, ODS and hepatotoxicity
• Not indicated for treatment of hypovolemic hyponatremia
• 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

• An intravenous combined V1a and V2 receptor antagonist approved for the short-term treatment of euvolemic and hypervolemic hyponatremia
  

Tolvaptan

• 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 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 and in patients with hepatic impairment as it may worsen liver function