What is the role of urea powder in treating hyponatremia?

Role of Urea Powder in Treating Hyponatremia

Urea powder is an effective and safe treatment option for fluid restriction-refractory hyponatremia, particularly in patients with SIADH, with a recommended starting dose of ≥30 g/day. 1

Mechanism and Indications

Urea works by inducing an osmotic water diuresis while promoting sodium retention, which effectively increases serum sodium levels in hyponatremic states. It is particularly useful in:

• Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH)
• Fluid restriction-refractory hyponatremia
• Chronic hyponatremia requiring long-term management
• Moderate to profound hyponatremia (<130 mmol/L)

Efficacy Evidence

Research demonstrates significant efficacy of urea in treating hyponatremia:

• 64.1% of patients achieve serum sodium ≥130 mmol/L within 72 hours of treatment 1
• Mean sodium increase of 6.9 ± 4.8 mmol/L at 72 hours, significantly greater than with preceding treatments 1
• Normalization of serum sodium by the fourth day of treatment in ICU patients with SIADH 2
• Effective for both acute and chronic hyponatremia management 3

Dosing and Administration

• Starting dose: ≥30 g/day 1, 4
• Administration: Oral powder dissolved in water or other beverages
• Duration: Can be used for both short-term and long-term management 5, 3
• Monitoring: Check serum sodium levels every 4-6 hours during active correction 6

Safety Profile

Urea has a favorable safety profile compared to other treatments:

• Low risk of overcorrection (8% of patients) 4
• No reported cases of hypernatremia or osmotic demyelination syndrome in studies 1
• Main side effect is distaste/poor palatability (22.7% of patients) 1
• Well-tolerated in long-term use, even in pediatric patients 5

Treatment Algorithm for Hyponatremia Management

1. Assess severity and chronicity of hyponatremia:

   • Mild (130-135 mmol/L)
   • Moderate (125-129 mmol/L)
   • Severe (<125 mmol/L) 6

2. First-line approach:

   • Fluid restriction (typically to <1000 mL/day) 6
   • Treat underlying cause if identified

3. When to consider urea:

   • When fluid restriction fails
   • In moderate to severe hyponatremia due to SIADH
   • When rapid correction is needed but must avoid overcorrection

4. Urea administration protocol:

   • Start with 30 g/day 1, 4
   • Dissolve in water or flavored beverage to improve palatability
   • Monitor serum sodium every 4-6 hours initially 6
   • Target correction rate: 4-6 mEq/L per day, not exceeding 8 mEq/L in 24 hours 6

5. If overcorrection occurs (>8 mEq/L in 24 hours):

   • Administer desmopressin 1-2 μg IV
   • Consider co-administration of free water 6

Advantages Over Alternative Treatments

• More effective than fluid restriction alone 1
• Lower risk of liver injury compared to vaptans (tolvaptan) 6
• Cost-effective compared to vaptans
• Suitable for long-term management 5, 3
• Does not increase ascites or edema (unlike hypertonic saline) 7

Practical Considerations

• Palatability is the main limitation; consider mixing with sweetened beverages
• Patient tolerance may affect adherence (53% discontinuation rate in one study) 4
• Monitor BUN levels, which will increase with treatment 4
• Particularly useful in patients who cannot tolerate fluid restriction

Urea represents a pathophysiologically sound approach to hyponatremia management by directly addressing the impaired free water excretion that characterizes conditions like SIADH, offering an effective alternative when conventional approaches fail.