From the Guidelines
Severe hyponatremia requires urgent treatment with careful correction of serum sodium levels, aiming to raise sodium by 4-6 mEq/L in the first 24 hours, with a maximum increase of 8 mEq/L per 24-hour period, as recommended by the most recent guidelines 1.
Treatment Approach
The treatment approach for severe hyponatremia should be based on the underlying cause, with the following key considerations:
- For patients with severe symptoms (seizures, coma), administer 3% hypertonic saline as a 100-150 mL bolus over 10-20 minutes, which can be repeated 1-2 times if symptoms persist.
- For hypovolemic hyponatremia, isotonic saline (0.9% NaCl) may be appropriate.
- For euvolemic or hypervolemic hyponatremia, fluid restriction to 800-1000 mL/day is often necessary.
- Vasopressin receptor antagonists like tolvaptan may be considered in specific cases of euvolemic or hypervolemic hyponatremia.
Monitoring and Adjustment
Rapid correction can lead to permanent neurological damage, so careful monitoring and adjustment of therapy based on frequent sodium measurements is essential for safe management. The goal is to raise sodium levels slowly and safely, without exceeding the recommended maximum increase of 8 mEq/L per 24-hour period.
Key Considerations
- The use of hypertonic saline should be reserved for short-term treatment of patients with symptomatic or severe hyponatremia, or those with imminent liver transplant 1.
- Albumin infusion may be considered in patients with severe hyponatremia, as it has been shown to improve serum sodium concentration 1.
- The treatment of underlying causes is crucial, and may include discontinuing offending medications, addressing SIADH, or treating volume depletion.
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 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 (see Table 2). For patients with a serum sodium of <130 mEq/L or <125 mEq/L, the effects at Day 4 and Day 30 remained significant (see Table 2).
The answer to severe hyponatremia is that tolvaptan can be used to treat it, as it has been shown to cause a statistically significant increase in serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.
- Key points:
- Tolvaptan is effective in treating severe hyponatremia.
- The effects of tolvaptan on serum sodium levels are significant in patients with serum sodium <130 mEq/L or <125 mEq/L.
- Tolvaptan can be used to treat hyponatremia resulting from various underlying causes, including heart failure, liver cirrhosis, and SIADH 2.
From the Research
Severe Hyponatremia Treatment
- Severe hyponatremia is a condition that requires prompt treatment to prevent complications such as cerebral edema 3, 4.
- The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline for the treatment of symptomatic hyponatremia, although this recommendation is based on a low level of evidence 3.
- A study comparing 100 mL and 250 mL NaCl 3% rapid bolus therapy as initial treatment of severe hypotonic hyponatremia found that the 250 mL bolus was more effective in increasing serum sodium levels without increasing the risk of overcorrection 4.
Hypertonic Saline Administration
- Hypertonic saline can be administered as a bolus injection or continuous infusion, although the optimal dose and administration modality are still debated 5.
- A central venous line may not be necessary for the administration of hypertonic saline, and desmopressin can be used concomitantly to prevent rapid correction of serum sodium 5.
- Reducing the bolus volume and reevaluating before repeating the bolus infusion may help prevent overcorrection, especially in severely symptomatic patients 3.
Vasopressin Excess and Hyponatremia
- Vasopressin excess is a common etiologic factor in hyponatremia, and vasopressin receptor antagonists such as lixivaptan, tolvaptan, and conivaptan can produce aquaresis to correct serum sodium concentration 6, 7.
- Vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, although uncertainty still exists regarding their optimal indications and potential complications resulting from their misuse 7.