From the Guidelines
Urea is a recommended treatment for SIADH-induced hyponatremia, particularly in cases where fluid restriction is ineffective or poorly tolerated, due to its ability to induce an osmotic diuresis and provide an osmotic load that helps protect against cerebral edema during correction 1.
Treatment Approach
When treating SIADH-induced hyponatremia with urea, the following approach can be taken:
- Start with a dose of 15-30 grams daily, divided into 2-4 doses, and titrate based on serum sodium response.
- Urea can be dissolved in water or juice (100-200 mL) to improve palatability, as it has a bitter taste.
- Commercial preparations like Ure-Na (15g packets) are available, or hospital pharmacies can compound it.
Key Considerations
- Treatment duration depends on whether the underlying SIADH is chronic or transient.
- Urea works by inducing an osmotic diuresis that increases free water excretion while preserving sodium, effectively counteracting the pathophysiology of SIADH.
- Monitor serum sodium levels regularly during treatment, aiming for a correction rate not exceeding 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome.
Comparison to Other Treatments
- Urea has advantages over other treatments, including lower cost than vaptans, fewer electrolyte disturbances than demeclocycline, and a lower risk of overly rapid sodium correction compared to hypertonic saline 1.
Clinical Context
- SIADH is a condition characterized by euvolemic hypoosmolar hyponatremia, with low serum osmolality and inappropriately high urine osmolality in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism.
- Early detection and appropriate management of SIADH can prevent severe hyponatremia, which can lead to seizures, coma, and death 1.
From the Research
Efficacy of Urea in Treating SIADH-Induced Hyponatremia
- Urea has been shown to be an effective treatment for SIADH-induced hyponatremia in several studies 2, 3, 4.
- In a study published in 2020, urea was found to increase serum sodium levels in patients with SIADH, with 62% of patients achieving normonatraemia at the end of the treatment episode 2.
- Another study published in 2019 found that urea was effective in treating fluid restriction-refractory hyponatremia, with 64.1% of patients achieving a serum sodium level of ≥130 mmol/L at 72 hours 3.
- A study published in 2012 found that urea administration increased serum sodium levels in critically ill patients with SIADH, with a significant increase in serum sodium from the second day of treatment 4.
Safety and Tolerability of Urea
- Urea has been found to be generally safe and well-tolerated in patients with SIADH-induced hyponatremia 2, 3, 4.
- Common side effects of urea include distaste, nausea, and polydipsia 2, 3.
- However, these side effects are usually mild and do not lead to treatment discontinuation 2, 3.
- Overcorrection of hyponatremia is a potential risk of urea treatment, but this can be mitigated by careful monitoring of serum sodium levels 5.
Comparison with Other Treatments
- Urea has been compared to other treatments for SIADH-induced hyponatremia, including fluid restriction, hypertonic saline, and vasopressin receptor antagonists 5, 6.
- A study published in 2012 found that urea was effective in treating SIADH-induced hyponatremia, but that vasopressin receptor antagonists may be a more convenient and efficient treatment option 5.
- A multidisciplinary algorithm for the treatment of SIADH-induced hyponatremia has been developed, which includes urea as a treatment option for mild or moderate hyponatremia 6.