Background Osmotic demyelination syndrome (ODS) is a rare but devastating complication of rapid correction of hyponatremia. Current guidelines recommend limiting the sodium correction rate to no more than 8 mmol/L per 24 hours, but this is based on expert opinion and small observational studies.

Methods We conducted a multicenter cohort study of patients admitted into hospital with hyponatremia at five academic hospitals in Toronto between April 1, 2010 and December 31, 2019. We identified all adult patients with hyponatremia (sodium <130 mmol/L) based on their initial serum sodium measured on presentation to the emergency department. The primary outcome was the rate of ODS. ODS cases were identified using medical record review and neuroimaging results. The secondary outcome was the rate of rapid correction of sodium (>8 mmol/L in any 24-hour period).

Results Our cohort included 21182 hospitalizations with hyponatremia. Approximately 50% were women, the average age was 68 years, and mean initial sodium was 124.6 mmol/L (SD 4.6) including 13.1% with sodium <120 mmol/L. Overall, rapid correction of sodium occurred in 3438 (17.9%) admissions. Despite the fact that 3438 experienced rapid correction, there were only 12 cases of ODS among our 21182 hospitalizations with hyponatremia. Cases of ODS had a markedly lower initial serum sodium (110.7 vs. 124.6 mmol/L), were younger (50 years vs 68 years), were more likely to have alcohol use disorder, and were more likely to have hypokalemia (58% vs 14%) compared to those without ODS.

Conclusions In the large multicenter study of patients with hyponatremia, “rapid” overcorrection was common (N=3438, 17.9%) but ODS was rare (N=12, 0.06%). The initial serum sodium was markedly lower for those with ODS compared to those without. Taken together, these results suggest that the severity of hyponatremia is a more important risk factor for ODS then the rate of correction.

The authors have declared no competing interest.

This study did not receive any funding.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Research Ethics Board approval was obtained from all participating hospitals. REB approval for University Health Network (Toronto), Sunnybrook Health Sciences Centre (Toronto), and St. Michael's Hospital (Toronto) was obtained through the integrated Clinical Trials Ontario platform, with St. Michael's Hospital as the "Board of Record". REB approval was also obtained from Trillium Health Partners (Mississauga) and Mount Sinai Hospital (Toronto). Clinical Trials Ontario Study ID 1394, https://www.ctontario.ca/

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