From the Guidelines
Hyponatremia should be treated based on its severity, with mild cases (Na 126-135 mEq/L) requiring only monitoring and water restriction, while more severe cases (Na <120 mEq/L) may necessitate water restriction, albumin infusion, and potentially vasopressin receptor antagonists or hypertonic saline. The management of hyponatremia depends on the underlying cause, with cirrhosis being a significant consideration 1.
Causes of Hyponatremia
- Depletion of sodium due to various reasons such as diuretics, gastrointestinal loss, or renal loss
- Excess water retention relative to sodium, often seen in conditions like heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Treatment Approaches
- For mild hyponatremia (Na 126-135 mEq/L), no specific management apart from monitoring and water restriction is recommended 1
- For moderate hyponatremia (Na 120-125 mEq/L), water restriction to 1,000 mL/day and cessation of diuretics is advised 1
- For severe hyponatremia (Na <120 mEq/L), a more severe restriction of water intake with albumin infusion may be necessary 1
- Vasopressin receptor antagonists can be used with caution for a short term (≤30 days) to raise serum sodium 1
- Hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia 1
Considerations for Correction
- The goal rate of increase of serum sodium should be 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period to prevent osmotic demyelination syndrome (ODS) 1
- Severe hyponatremia at the time of liver transplantation increases the risk of ODS, and multidisciplinary coordinated care may help mitigate this risk 1
From the FDA Drug Label
Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) 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 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. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies
The causes of hyponatremia mentioned in the label include:
- Heart failure
- Liver cirrhosis
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
- Other underlying causes
The treatment of hyponatremia mentioned in the label is:
- Tolvaptan tablets, which can be initiated at a dose of 15 mg once daily and titrated up to 60 mg once daily as needed to achieve the desired level of serum sodium
- Fluid restriction, which should be avoided during the first 24 hours of therapy and can be resumed or initiated as clinically indicated thereafter
- Monitoring of serum sodium and volume status, particularly during initiation and titration of tolvaptan therapy 2 2
From the Research
Causes of Hyponatremia
- Hyponatremia is often caused by elevated levels of arginine vasopressin (AVP) hormone, which can occur in various clinical conditions such as syndrome of inappropriate secretion of AVP, volume depletion, postoperative states, heart failure, cirrhosis, neuroendocrine disorders, and trauma 3
- It can also be caused by water retention, with most patients having hypovolemic, euvolemic, or hypervolemic hyponatremia 4
- Concomitant diseases and therapies, such as diabetes, chronic kidney disease, and heart failure, along with diuretics, antidepressants, and proton pump inhibitors, are common causes of hyponatremia in the community 5
- In patients with stroke, hyponatremia can be attributed to the administration of hypotonic solutions and drugs, poor solute intake, infections, and stroke-related conditions or complications 5
Symptoms of Hyponatremia
- Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma) 4
- Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia 4
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 4
Treatment of Hyponatremia
- For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 4
- Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 4
- Severely symptomatic hyponatremia is a medical emergency and should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 4, 3
- Fluid restriction and loop diuretics are frequently employed to treat volume overload, while vasopressin receptor antagonists provide prompt and effective water diuresis and increase in serum sodium concentration in both euvolemic and hypervolemic hyponatremia 3, 6
- In patients with stroke, therapeutic options are based on the duration and symptoms of hyponatremia, with hypertonic saline administration recommended for acute or symptomatic hyponatremia 5