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Should More Lenient Guidelines be Considered for the Treatment Hyponatremia?

Updated: Apr 9, 2023

AI-generated hyponatremia

Hyponatremia, a common electrolyte imbalance in hospitalized patients, can independently predict mortality and is linked to longer hospital stays and higher costs. Inadequately treated hyponatremic encephalopathy, a severe potential complication, can lead to death or irreversible brain damage. Hypertonic saline is a safe and effective treatment for hyponatremia. However, a rare and serious complication from excessive correction of chronic hyponatremia is cerebral demyelination. Rapid increases in serum sodium in animal and human studies can cause brain injury in the context of chronic hyponatremia. Cerebral demyelination is a multifactorial condition, primarily reported in patients with severe and chronic hyponatremia and additional risk factors. Osmotic Demyelination Syndrome (ODS) is the term used for cerebral demyelination following hyponatremia correction, as it is believed that the correction is the primary causative factor and demyelination is mostly preventable with slow sodium correction. However, this may not be accurate since cases of cerebral demyelination have been reported with slow correction or without hyponatremia. Safe limits for hyponatremia correction remain uncertain. Clinical practice guidelines recommend limits of 8-10 mmol/l per 24 hours for ODS prevention, with serum sodium level reduction using free water or desmopressin if limits are exceeded. Data regarding the risk of ODS development in hyponatremic patients and its relationship to rapid hyponatremia correction are limited.

Have you ever seen a case of Osmotic Demyelination Syndrome

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  • No

  • Not sure

In a recent issue of NEJM Evidence, MacMillan et al. examined the occurrence of Osmotic Demyelination Syndrome (ODS) and its association with the fast correction of hyponatremia in a comprehensive multicenter study involving over 22,000 patients admitted with low serum sodium levels (<130 mmol/l) to emergency departments at several hospitals over an 11-year period. A considerable portion (17.7%) of patients experienced rapid hyponatremia correction, defined as an increase of over 8 mmol/l within 24 hours. Imaging revealed ODS in 12 patients, but only 9 were categorized as "definite cases" [1].

The prevalence of ODS increased as initial hyponatremia severity worsened, with 0.05%, 0.3%, and 2.6% for serum sodium levels below 130 mmol/l, 120 mmol/l, and 110 mmol/l, respectively. Hypokalemia was also identified as a potential risk factor, present in 58% of ODS cases, although the statistical certainty was not strong. The study found no correlation between the fast correction of hyponatremia and ODS development, as most cases (7 out of 12) had slow correction rates, and half of the cases were treated with desmopressin. Hospital mortality rates were higher for patients with slow correction compared to those with rapid correction (9.2% vs. 5.1%). Due to a lack of information on the five patients with ODS and rapid correction, the study could not assess the role of correction in comparison to other risk factors.

Do you think that more lenient guidelines for hyponatremia treatment be considered.

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  • No

  • Not sure

This comprehensive study reveals that ODS is extremely rare and unrelated to rapid correction. Current hyponatremia treatment guidelines are increasingly restrictive, focusing on limiting correction rates to prevent ODS. However, this study questions the necessity of these limitations, as strict adherence may result in insufficient treatment, frequent sodium monitoring, serum sodium relowering with desmopressin, prolonged hospital stays, and higher costs without clinical benefits. The study suggests considering more lenient guidelines, allowing acute serum sodium increases with hypertonic saline to prevent neurological complications. Rapid intermittent bolus with hypertonic saline has been effective in correcting hyponatremia, and a 48-hour sodium correction limit of 15 to 20 mmol/l could be more beneficial than current 24-hour limits, providing greater flexibility for treatment while maintaining safety.


1. MacMillan TE, Shin S, Topf J, et al. Osmotic demyelination syndrome in patients hospitalized with hyponatremia. NEJM Evid2023: 2(4). DOI: 10.1056/EVIDoa2200215.

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