Risk factors for undercorrection in severe hyponatremia: a post-hoc analysis of the SALSA trial

Hyponatremia undercorrection (i.e., nonoptimal correction) is insufficient to resolve cerebral edema and is associated with poor clinical outcomes. This study aimed to identify risk factors of undercorrection under controlled hypertonic saline treatment.

This post-hoc analysis of the prospective randomized controlled SALSA (Efficacy and Safety of Rapid Intermittent Correction Compared With Slow Continuous Correction With Hypertonic Saline) trial included 172 patients with glucose-corrected serum sodium (sNa) ≤125 mmol/L after excluding six without follow-up sNa measurements. Undercorrection was defined as sNa increases of <5 or <10 mmol/L within 24 or 24-48 hours, respectively, or failure to reach 130 mmol/L within 24-48 hours.

The mean age was 72.8 years; the mean sNa level was 118.2 mmol/L. Undercorrection occurred in 15.1% of patients (26/172). These patients received more hypertonic saline (932 mL vs. 486 mL, p < 0.001) and had lower urine output over 48 hours (2,647 mL vs. 4,117 mL, p = 0.004). Risk factors included higher urine osmolality and serum calcium and creatinine levels, and lower body mass index, systolic blood pressure, white blood cell count, and albumin levels. Although most etiologic categories were not independently associated with undercorrection, thiazide use was inversely associated with undercorrection in the multivariable analysis. Undercorrection did not increase mortality but was associated with prolonged hospitalization (19.6 days vs. 7.8 days, p = 0.01).

Despite protocol-based hypertonic saline treatment, undercorrection occurred in 15% of patients and was associated with patient-specific risk factors. These findings emphasize the need for individualized sodium correction strategies to optimize patient outcomes.