Reference: Ann Intern Med. 2026 Mar;179(3):330-339
Practice Point: Faster sodium correction rates (8-12 mEq/L per 24 hours) may be associated with better outcomes in adults with severe hyponatremia.
EBM Pearl: Residual confounding is unavoidable in observational studies. Confidence in findings improves when multiple analytic approaches and sensitivity analyses point in the same direction.
We’ve probably all heard some version of the statistic that only half of what we learn in our medical training is true, but we don’t know which half is which. The truth is that a lot of what we "know" becomes outdated in time, as we accumulate more evidence and understanding. Medicine evolves, and staying current means being willing to question long-held assumptions.
One of those assumptions is that rapid overcorrection of severe hyponatremia is inherently dangerous. While some level of concern about osmotic demyelination syndrome, a serious complication of rapid sodium overcorrection that can lead to serious neurologic damage or death, is still warranted, newer data are challenging how cautious we need to be about the speed of correction. A 2025 systematic review and meta-analysis reported that faster correction rates (up to 12 mEq/L in the first 24 hours) were associated with lower in-hospital mortality compared with slower correction in adults with severe hyponatremia.
Building on this, a 2026 retrospective cohort study in Annals of Internal Medicine evaluated 13,988 hospitalized adults (median age 74 years) with severe hyponatremia (serum sodium ≤ 120 mEq/L) across 21 U.S. hospitals. Common comorbidities included heart failure (24%), liver disease (18%), malnutrition (15%), alcohol dependence (14%), and metastatic cancer (10%).
Patients were grouped by 24-hour sodium correction:
- Slow: < 8 mEq/L
- Moderate: 8-12 mEq/L
- Fast: > 12 mEq/L
The primary outcome was a composite of 90-day mortality and delayed neurologic complications, including demyelination, seizures, paralysis, or altered consciousness. Results showed that 90-day mortality rates were reduced with faster sodium correction: 8% in the fast group, 14% in the moderate group, and 24% in the slow group. Rates of delayed neurologic events were 4% each in the fast and moderate groups and 5% in the slow group.
While osmotic demyelination syndrome is a concern with rapid correction, the incidence was very low (0.12%-0.17%) and was similar between faster and slower correction rates. Consistent findings were also noted in the 2025 systematic review (osmotic demyelination syndrome event rate 0.3%).
As with any observational study, confounding is a concern. In this study, authors utilized several methods, such as stratification and regression, in an attempt to control for confounding. But, despite these best efforts, residual confounding always remains. (We can’t control everything, and we don’t know what we don’t know!) However, in this study, complex statistical methods (such as targeted maximum likelihood estimation) were used that can overcome some of the weaknesses associated with regression analyses, propensity score methods, and inverse probability weighting. In addition, several sensitivity analyses were conducted to confirm the primary findings and to try to capture even more of the residual confounding. Although we can’t establish cause and effect, these methods do improve internal validity and work best when layered alongside other statistical methods (think "Swiss cheese" approach to the use of statistics).
Most people squirm at the idea of major practice change; however, EBM requires an open mind and willingness to change practice based on new evidence. This is one of those moments in which evolving evidence may challenge what we’ve always been taught. Embrace the challenge to change: In adults with severe hyponatremia, faster sodium correction (8-12 mEq/L per 24 hours) appears to be associated with a lower risk of 90-day mortality without increased risk of neurologic damage. The "slower is always safer" mindset may be overdue for a rethink.
For more information, see the topic Hyponatremia in Adults - Approach to the Patient in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed. Edited by Katharine DeGeorge, MD, MS, Executive Editor at DynaMed and Professor of Family Medicine at the University of Virginia; Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Rich Lamkin, MPH, MPAS, PA-C, Senior Clinical Writer at DynaMed; Claire Symanski, PhD, Medical Editor and Team Lead for ENT at DynaMed; Michael Butler, PhD, Medical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.