Clinical Question: Does targeted correction of chronic hyponatremia in hospitalized patients reduce 30-day mortality or rehospitalization compared with routine care?
Background: Chronic hyponatremia is associated with falls, cognitive impairment, fractures, and increased mortality, but it remains unclear whether hyponatremia itself worsens outcomes or reflects underlying illness severity. Observational studies suggest normalization of sodium may improve outcomes, but prospective randomized evidence has been limited.
Study Design: Pragmatic, multicenter, randomized, controlled, parallel-group, superiority trial with blinded outcome assessment.
Setting: Nine university and regional hospitals in five European countries from August 2018 to April 2024
Synopsis: This randomized controlled trial enrolled 2,173 hospitalized adults with chronic hypotonic hyponatremia (serum sodium less than 130 mmol/L; median, 127 mmol/L). Patients were assigned to either a targeted plasma-sodium-correction strategy based on guideline-directed diagnostics and treatment, or standard care directed by treating physicians. The primary outcome was 30-day death or rehospitalization. Targeted treatment achieved higher rates of normonatremia (60.4% versus 46.2%) and greater sodium correction than standard care but did not reduce the primary outcome (20.5% versus 21.8%; absolute difference -1.3 percentage points, P=0.45). Mortality, rehospitalization, quality of life, neurocognitive outcomes, falls, fractures, and hospital length of stay were also similar between groups. Overcorrection occurred slightly more often with the targeted intervention (2.3% versus 1.4%), though there were no occurrences of osmotic demyelination syndrome. These results differ from prior observational data linking sodium normalization to improved outcomes and suggest that intensified inpatient correction alone may not improve short-term clinical outcomes. Limitations include the inability to blind treatments, the predominance of moderate rather than severe hyponatremia, and the interventions’ duration during the patients’ hospitalization.
Bottom Line: In hospitalized patients with chronic moderate hyponatremia, targeted sodium correction improved normalization rates but did not reduce 30-day mortality or rehospitalization compared with usual care.
Citation: Refardt J, et al. A randomized trial of targeted hyponatremia correction in hospitalized patients. NEJM Evid. 2026;5(3):EVIDoa2500086. doi:10.1056/EVIDoa2500086
Dr. Magee
Dr. Magee is an academic hospitalist and division chief of hospital medicine at MedStar Washington Hospital Center and an associate professor of medicine at Georgetown University School of Medicine, both in Washington, D.C.