From the Guidelines
Hyponatremia treatment should prioritize correcting the underlying cause, and for severe symptomatic cases, hypertonic saline administration should be limited to those with life-threatening manifestations, with a correction rate not exceeding 8-10 mmol/L per 24 hours, as recommended by the most recent guidelines 1. The main causes of hyponatremia include excessive water intake, medications (diuretics, antidepressants, antipsychotics), medical conditions (heart failure, kidney disease, liver cirrhosis, adrenal insufficiency, hypothyroidism), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and excessive sweating without adequate salt replacement.
Treatment Approaches
- For mild cases, fluid restriction to 1-1.5 liters daily may be sufficient.
- Moderate to severe cases may require intravenous sodium chloride solution (0.9% or 3% hypertonic saline for severe cases).
- Medications like tolvaptan (vasopressin receptor antagonist) may be used for SIADH.
- Treating underlying conditions is essential.
- Patients should be monitored with regular blood tests during treatment.
- Dietary adjustments may include increasing salt intake while reducing water consumption.
Key Considerations
- Severe symptomatic hyponatremia (seizures, altered consciousness) requires immediate medical attention as it can be life-threatening.
- The use of hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant (LT) 1.
- When correction of chronic hyponatremia is indicated in patients with cirrhosis, 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 (ODS) 1.
Recent Guidelines
The most recent guidelines from 2021 recommend that mild hyponatremia in cirrhosis without symptoms does not require specific management apart from monitoring and water restriction, while water restriction and cessation of diuretics are recommended for moderate hyponatremia, and a more severe restriction of water intake with albumin infusion is recommended for severe hyponatremia 1.
Correction Rate
The correction rate of serum sodium should not exceed 8-10 mmol/L per 24 hours, as recommended by the guidelines 1.
Medications
Medications like tolvaptan should be used with caution only for a short term (≤30 days) 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) The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. 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 label include:
- Heart failure
- Liver cirrhosis
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
- Other underlying causes
The treatment of hyponatremia with tolvaptan involves:
- Initiating therapy in a hospital to evaluate the therapeutic response and avoid overly rapid correction of serum sodium
- Starting with a dose of 15 mg once daily and increasing to 30 mg once daily, then to 60 mg once daily, as needed
- Avoiding fluid restriction during the first 24 hours of therapy
- Monitoring serum sodium and volume status closely during treatment and after discontinuation 2, 2, 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 be categorized into three types based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia 3
- The syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of all cases of hyponatremia 4
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, 5, 6
- The goal of treatment is to increase the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours, but by no more than 10 mEq/L within the first 24 hours 3
- Vasopressin receptor antagonists, such as vaptans, have been introduced as a specific and direct therapy for SIADH, and appear to be advantageous due to their efficiency and reliability, but require careful monitoring to prevent overly rapid correction of hyponatremia 4, 7