Ure-Na (Urea) for Treating Hyponatremia
Urea is an effective and safe treatment option for fluid restriction-refractory hyponatremia, particularly in patients with SIADH who have failed or are unable to undergo fluid restriction. 1, 2
Mechanism and Indications
- Urea works as an osmotic agent that increases solute intake, enhancing free water excretion in the kidneys, which is particularly beneficial in SIADH 3
- Urea is most appropriate for euvolemic hyponatremia, particularly SIADH, when fluid restriction alone is insufficient 1, 2
- It can be considered as a second-line treatment after fluid restriction failure or as first-line treatment in selected cases 2
Efficacy and Safety Profile
- Urea has been shown to successfully increase serum sodium levels in approximately 64% of patients with hyponatremia within 72 hours 2
- Studies demonstrate that urea results in significantly lower mortality and neurological impairment compared to overcorrection with vasopressin antagonists or hypertonic saline 4
- Urea minimizes the risk of osmotic demyelination syndrome even when sodium correction occurs rapidly, providing a safety advantage over other treatments 4
- The typical correction rate with urea is approximately 2 mEq/L per day, making it suitable for gradual correction of chronic hyponatremia 5
Dosing Recommendations
- The recommended starting dose is ≥30 g/day for moderate to profound hyponatremia 2
- In neurosurgical patients, 40 g of urea in 100-150 mL of normal saline every 8 hours, in addition to continuous infusion of normal saline at 60-100 mL/h for 1-2 days, has been effective 6
- Factors associated with greater sodium correction include:
- Older age
- Lower baseline plasma sodium
- Higher cumulative urea dose
- Concurrent fluid restriction (particularly in the first 48 hours) 7
Advantages Over Other Treatments
- Unlike vasopressin antagonists or hypertonic saline, urea has a lower risk of causing osmotic demyelination syndrome even with rapid correction 4
- Urea is particularly useful in patients with SIADH who have failed fluid restriction 2
- Free water restriction combined with increased solute intake (e.g., urea) is considered the most effective therapy for SIADH 3
Side Effects and Limitations
- The most common side effect is distaste, reported in approximately 22.7% of patients 2
- Patient intolerance may lead to discontinuation in some cases (about 11%) 5, 7
- Overcorrection (increase >8 mEq/L in 24 hours) can occur in approximately 3-8% of patients, requiring careful monitoring 5, 7
- Outpatient affordability may limit its use in some settings 5
Monitoring Recommendations
- Monitor serum sodium levels regularly during treatment to prevent overcorrection 1
- The rate of correction should not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1
- For patients with advanced liver disease, alcoholism, malnutrition, or prior encephalopathy, use more cautious correction rates (4-6 mmol/L per day) 1
Special Considerations
- Urea is particularly valuable in neurosurgical patients with hyponatremia, where distinguishing between SIADH and cerebral salt wasting is critical 6, 1
- In cerebral salt wasting, fluid restriction should be avoided as it can worsen outcomes; urea can be beneficial in these cases when combined with appropriate volume replacement 6, 1
- Simultaneous administration of desmopressin with urea may be considered in high-risk patients to prevent overly rapid sodium correction 3