From the Guidelines
Hyponatremia should be treated based on its etiology, chronicity, severity, and urgency, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome, as recommended by the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.
Treatment Approach
The treatment of hyponatremia depends on whether it is acute or chronic, as well as the underlying cause. For acute hyponatremia, rapid correction may be necessary to prevent cerebral edema, whereas chronic hyponatremia requires more gradual correction to avoid overcorrection and the risk of osmotic demyelination syndrome.
- Hypovolemic hyponatremia is treated by discontinuing diuretics and/or laxatives and providing fluid resuscitation, typically with 5% IV albumin or crystalloid solution, as suggested by the 2021 practice guidance 1.
- Euvolemic hyponatremia should be managed based on the specific underlying cause, which may involve addressing SIADH, adrenal insufficiency, or other conditions.
- Hypervolemic hyponatremia is treated with fluid restriction, reduction or discontinuation of diuretics and laxatives, administration of hyperoncotic albumin, and/or vasopressin receptor antagonists (“vaptans”), as recommended by the 2021 practice guidance 1.
Correction of Serum Sodium Levels
- Correction of serum sodium levels should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as cautioned by the 2018 guidelines from the Journal of Hepatology 1 and the 2021 practice guidance 1.
- Sodium levels should be monitored every 2-4 hours during correction to ensure safe and effective management.
Underlying Causes
- Underlying causes of hyponatremia, such as offending medications (thiazide diuretics, SSRIs, carbamazepine), SIADH, adrenal insufficiency, or heart failure, must be addressed to effectively manage the condition, as emphasized by the 2021 practice guidance 1.
From the FDA Drug Label
14 CLINICAL STUDIES 14. 1 Hyponatremia 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 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
- Tolvaptan is effective in treating hyponatremia by increasing serum sodium levels.
- The studies showed a statistically significant increase in serum sodium levels in patients treated with tolvaptan compared to placebo.
- Tolvaptan was effective in patients with serum sodium levels <135 mEq/L, <130 mEq/L, and <125 mEq/L.
- The effect of tolvaptan was seen across all disease etiology subsets, including heart failure, liver cirrhosis, and SIADH 2.
From the Research
Definition and Prevalence of Hyponatremia
- Hyponatremia is defined as a serum sodium concentration <135mmol/l 3
- It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 4
- Hyponatremia can lead to a wide spectrum of clinical symptoms, from mild to severe or even life-threatening, and is associated with increased mortality, morbidity, and length of hospital stay 3
Causes and Classification of Hyponatremia
- Hyponatremia most commonly results from water retention 4
- It can be classified into three categories based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, and hypervolemic hyponatremia 4
- The approach to managing hyponatremia should consist of treating the underlying cause 4
Symptoms and Signs 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
- 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
- Vasopressin receptor antagonists are promising new therapeutic options for the treatment of euvolemic and hypervolemic hyponatremia 5, 6, 7
- Hypertonic saline is reserved for patients with severely symptomatic hyponatremia 4
- The goal of treatment is to increase the serum sodium level by 4-6 mEq/L within 1-2 hours, but not to exceed a correction limit of 10 mEq/L within the first 24 hours 4