Clinical factors associated with hyponatremia correction during treatment with oral urea

Background. Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. Methods. This was a retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium <135 mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. Results. We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as the only treatment in 27 treatment episodes (17%). A median dose of 30 g/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134 mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (beta 0.09, 95% CI 0.02-0.16), lower baseline plasma sodium (beta -0.65, 95% CI -0.78 to -0.62) and higher cumulative urea dose (beta 0.03, 95% CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48 h of treatment (beta 1.81, 95% CI 0.40-3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified and oral urea was discontinued in 11 cases (11%) due to side effects. Conclusion. During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.