From the Guidelines
Hyponatremia should be treated based on its severity and underlying cause, with the goal of correcting serum sodium levels while preventing osmotic demyelination syndrome, as recommended by the most recent guidelines 1.
Causes of Hyponatremia
The causes of hyponatremia can be diverse, including:
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion, which is characterized by euvolemic hypoosmolar hyponatremia, low serum osmolality, and inappropriately high urine osmolality 1
- Heart failure, cirrhosis, and nephrotic syndrome, which can lead to hypervolemic hyponatremia
- Adrenal insufficiency, hypothyroidism, and certain medications, such as thiazide diuretics, SSRIs, and carbamazepine, which can cause hyponatremia through various mechanisms
Treatment of Hyponatremia
Treatment of hyponatremia depends on its severity and underlying cause. For mild cases (sodium >125 mEq/L), fluid restriction to 800-1000 mL/day is often sufficient. For moderate to severe symptomatic hyponatremia, 3% hypertonic saline may be administered at 100-150 mL over 10-20 minutes, which can be repeated if necessary. The correction rate should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as recommended by recent guidelines 1. Specific medications, such as tolvaptan (15-60 mg daily) for SIADH-related hyponatremia, or fludrocortisone (0.1 mg daily) for salt-wasting conditions, may also be used.
Monitoring and Prevention
Regular monitoring of serum sodium levels is essential during correction. Underlying causes must be addressed, such as adjusting heart failure medications, treating adrenal insufficiency, or discontinuing offending drugs. Vasopressin receptor antagonists can be used with caution for a short term (≤30 days) in patients with cirrhosis, but their use should be carefully considered due to potential risks 1.
Key Considerations
- Severe hyponatremia (<120 mEq/L) at the time of liver transplantation increases the risk of osmotic demyelination syndrome, and multidisciplinary coordinated care may mitigate this risk 1
- The goal rate of increase of serum sodium is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, to ameliorate the risk of osmotic demyelination syndrome 1
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 causes of hyponatremia mentioned in the study include:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Other underlying causes
The treatment of hyponatremia mentioned in the study is:
- Tolvaptan, a medication that can be taken orally at an initial dose of 15 mg once daily, with possible increases to 30 mg and 60 mg once daily
- Fluid restriction, which may be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium 2
From the Research
Causes of Hyponatremia
- Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 3
- It can occur through any mechanism that produces a relative excess of body water to body sodium 4
- Increased vasopressin secretion due to nonosmotic stimuli leads to decreased electrolyte-free water excretion with resulting water retention and hyponatremia 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) 3
- Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia 3
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3
Treatment of Hyponatremia
- For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 3
- Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 3
- Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency and should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 6, 7
- Fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary 7
- Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in different guidelines 7
Diagnosis of Hyponatremia
- Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia 7
- Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status 7
- Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach 7