Meta-analysis: Urea May be Effective for the Treatment of SIADH-Induced Hyponatremia
15 Nov, 2024 | 14:01h | UTCBackground: Hyponatremia, defined as a serum sodium level below 135 mEq/L, is the most common electrolyte disorder in clinical practice, associated with increased mortality and prolonged hospital stays. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a frequent cause of euvolemic hyponatremia, particularly among hospitalized patients. Traditional treatments like fluid restriction and hypertonic saline have limitations, and guidelines are inconsistent regarding their use. Urea, an osmotic diuretic, has been proposed as an alternative therapy but is underutilized due to concerns about efficacy, safety, and patient tolerability.
Objective: To evaluate the effectiveness and safety of urea in treating hyponatremia caused by SIADH.
Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches of MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar up to November 2023 identified studies involving patients with SIADH-related hyponatremia treated with oral or nasogastric urea. Inclusion criteria encompassed clinical trials and observational studies reporting outcomes on serum sodium levels, symptom resolution, or adverse effects.
Results: Sixteen observational studies involving 518 patients (430 treated with urea) met inclusion criteria. Urea treatment significantly increased serum sodium levels (mean difference [MD], 9.21 mEq/L [95% CI, 7.36-11.06]; P < 0.01) despite high heterogeneity (I² = 89%). Subgroup analyses showed significant sodium increases at 24 hours and at 2, 3, 5, 7, 14 days, and 1 year post-treatment. Patients with severe hyponatremia (<120 mEq/L) experienced greater sodium increases (MD, 18.04 mEq/L [95% CI, 13.68-22.39]) compared to those with moderate (120-129 mEq/L) or mild (130-135 mEq/L) hyponatremia. Urea’s efficacy was comparable to fluid restriction (MD, 0.81 mEq/L [95% CI, –0.93 to 2.55]; P = 0.4) and vaptans (MD, –2.43 mEq/L [95% CI, –6.31 to 1.45]; P = 0.2), and superior to no treatment (MD, 7.99 mEq/L [95% CI, 6.25-9.72]; P < 0.01). Adverse events were minor; poor palatability was the most common complaint.
Conclusions: Urea is an effective and safe treatment for SIADH-induced hyponatremia, significantly increasing serum sodium levels, particularly in severe cases. It offers a viable alternative to fluid restriction and vaptans with minimal adverse effects.
Implications for Practice: Urea should be considered a valuable treatment option for SIADH-induced hyponatremia, especially in resource-limited settings or when other therapies are contraindicated or poorly tolerated. Its cost-effectiveness and ease of administration may improve patient outcomes and reduce healthcare costs.
Study Strengths and Limitations: Strengths include a comprehensive search strategy and inclusion of diverse studies across multiple settings. Limitations are the reliance on observational studies due to the absence of randomized controlled trials, significant heterogeneity among studies, and the potential for publication bias.
Future Research: Randomized controlled trials are necessary to confirm urea’s efficacy and safety, establish standardized dosing regimens, and develop strategies to enhance palatability and patient adherence.