From the Guidelines
The workup of chronic hyponatremia should prioritize determining the underlying cause and volume status, with treatment goals focused on correcting sodium levels at a rate not exceeding 8 mEq/L per 24 hours to prevent osmotic demyelination syndrome, as recommended by the most recent guidelines 1.
Initial Assessment
The initial step in managing chronic hyponatremia involves a thorough clinical assessment, including a detailed history, physical examination, and laboratory testing. Key laboratory tests should include serum sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, and osmolality, as well as urine sodium and osmolality. Assessment of volume status is crucial, categorizing the patient as hypovolemic, euvolemic, or hypervolemic.
Treatment Approach
- For hypovolemic hyponatremia, treatment focuses on volume repletion with isotonic saline.
- In euvolemic hyponatremia, the most common cause is the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which requires fluid restriction (typically 800-1000 mL/day) and possibly salt tablets. Medications like tolvaptan may be considered for resistant cases.
- Hypervolemic hyponatremia, often seen in heart failure or cirrhosis, requires sodium and fluid restriction along with diuretics. According to the 2021 practice guidance by the American Association for the Study of Liver Diseases 1, water restriction to 1,000 mL/day and cessation of diuretics is recommended for moderate hyponatremia, and a more severe restriction of water intake with albumin infusion is recommended for severe hyponatremia.
Correction Rates and Monitoring
Correction of chronic hyponatremia should aim for a rate of increase of serum sodium of 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, as emphasized in the guidelines 1. Frequent monitoring of serum sodium (every 4-6 hours initially) is essential during correction to prevent overcorrection and osmotic demyelination syndrome.
Underlying Cause
Identifying and addressing the underlying cause of chronic hyponatremia, such as discontinuing offending medications or treating hypothyroidism or adrenal insufficiency, is fundamental to successful management. The use of vasopressin receptor antagonists can raise serum sodium during treatment but should be used with caution and only for a short term (≤30 days) 1. Hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant, with careful consideration to avoid rapid correction 1, 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 work up of chronic hyponatremia involves treating patients with tolvaptan, starting with an initial oral dose of 15 mg once daily, which can be increased to 30 mg once daily, then to 60 mg once daily, until either the maximum dose or normonatremia (serum sodium >135 mEq/L) is reached.
- Key points to consider in the work up include:
- Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
- Patients can resume or initiate fluid restriction (defined as daily fluid intake of ≤1.0 liter/day) as clinically indicated after the first 24 hours.
- Serum sodium concentrations should be determined at 8 hours after study drug initiation and daily up to 72 hours, within which time titration is typically completed.
- Treatment should be maintained for 30 days with additional serum sodium assessments on Days 11, 18, 25, and 30 3.
From the Research
Evaluation of Chronic Hyponatremia
- The evaluation of chronic hyponatremia begins with a detailed history and physical examination to assess the severity of symptoms and fluid volume status 4.
- Appropriate urine and serum studies, including serum sodium, urine electrolytes, and serum and urine osmolality, can contribute to the evaluation and classification of the disorder 4, 5.
- Point-of-care ultrasonography is an important adjunct to physical assessment in estimation of volume status 5.
Classification of Hyponatremia
- Hyponatremia can be classified into three categories based on fluid volume status: hypovolemic, euvolemic, and hypervolemic hyponatremia 6, 5.
- The classification of hyponatremia is crucial in determining the underlying cause and guiding treatment decisions 6, 7.
Treatment of Chronic Hyponatremia
- The treatment of chronic hyponatremia depends on the underlying cause, severity of symptoms, and fluid volume status 6, 7.
- Treatment options for correcting hyponatremia in advanced liver disease may include water restriction, hypokalemia correction, and administration of vasopressin antagonists, albumin, and 3% saline 7.
- Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 6.
- Severely symptomatic hyponatremia requires immediate correction with 3% saline or bolus hypertonic saline to reverse hyponatremic encephalopathy 6, 7.
Complications of Hyponatremia
- Chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 6.
- Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death 6, 7.
- Hyponatremia affects approximately 5% of adults and 35% of patients who are hospitalized, and is associated with increased hospital stay and mortality 6.