We read with interest Drs. Rondon-Berrios and Sterns' editorial regarding the treatment of hyponatremia in the May issue of ASN Kidney News (1) on the original investigation published in March 2023 in NEJM Evidence (2). This is a 10-year retrospective examination of hyponatremia at five hospitals in Toronto, Ontario, Canada. We found 22,858 medicine admissions with a serum sodium <130 mmol/L with only 12 cases of osmotic demyelination syndrome (ODS) despite exceeding sodium correction of 8 mmol/L in 24 hours in 18% of admissions. The patients with an initial sodium of <110 mmol/L had a markedly higher proportion of ODS.
The authors criticized our inclusion of a low-risk population. They claimed that patients with an initial sodium over 120 mmol/L are known to be at low risk for ODS, but do not support this assertion with any references. Most of the largest prior case series on patients with hyponatremia excluded patients with initial sodium over 125 mmol/L (3–8). We included patients in this group to empirically evaluate the risk of ODS. More than one patient in our ODS cohort came from this purportedly “low risk” group. While our study indeed confirms that the risk of ODS is low in patients with an initial sodium between 120 and 129 mmol/L, ODS did occur, and the risk may not be as “vanishingly low” as the authors suggested. Additionally, in the authors' own review of case reports of ODS with slow correction of hyponatremia, one-quarter of their cases came from patients with initial sodium levels over 120 mmol/L (9).
The editorialists state that patients with acute water intoxication should have been excluded from the study and claim that this group is at very low risk of ODS, although they do not provide support references. Determining the acuity of hyponatremia is not possible in a cohort study, as patients rarely have sodium measurements on the days preceding admission. Current guidelines recognize this and recommend that when the acuity of hyponatremia is uncertain, it should be treated as chronic, which is the approach we took in our study and the approach the authors used in their own publications (2, 9). Additionally, in a systematic review of patients with hyponatremia due to excessive water intake, 39% of symptomatic patients had symptoms for more than 48 hours (10). The meta-analysis also found a 3% rate of ODS, questioning the assertion that this population is low risk.
The authors also question how we determined the rate of sodium correction. We defined overcorrection as any change in sodium of >8 mmol/L occurring within any period of 24 hours or less, until the sodium reached 130 mmol/L, or the patient was discharged; this approach has been used previously (8). While there are many ways of measuring sodium overcorrection, there is no consensus on the optimal method, and others have used maximum correction rates (11). There is no evidence that defining overcorrection using fixed time points is more closely linked to the risk of ODS than using maximum correction rates (11). Most patients do not have sodium measurements at exactly 24 and 48 hours, which is partly why we did not use these to define overcorrection in our study.
The authors state that ODS is a clinical diagnosis and that only the most severe cases show up on brain imaging. They do not provide any references to support this claim. In Lohr's review of ODS, only 12 of the 74 cases were a “clinical diagnosis” (12). In the study by George et al. on the rapid correction of hyponatremia, they found nine cases of ODS; all of them were diagnosed by MRI-based brain imaging (5). In the authors' recent review, 20 of the 21 cases of ODS had MRI findings consistent with the diagnosis (9).
The authors conclude by saying the current approach to severe hyponatremia of using DDAVP [desmopressin] should not be relaxed and that we should ask ourselves what percentage risk of ODS would we be willing to accept for our patients or family members so that they can be discharged from the hospital 1 day or 2 days earlier. They answer their own question as “none.” In our opinion, the authors are too quick to dismiss the potential negative consequences to slowing the rate of sodium correction, especially in patients at lower risk of ODS. From a patient perspective, more frequent blood draws can be painful and uncomfortable, and many would value a shorter length of stay. From a health systems perspective, increasing length of stay can contribute to overcrowding, increased health care costs, and increased ICU mortality (13, 14). Most concerning is the recent finding that slower sodium correction is associated with increased mortality (15). This suggests that determining the ideal rate of correction may require prospective, interventional trials to determine and balance the harms and benefits of any strategy.
References
- 1.↑
Rondon-Berrios H, Sterns RH. We do not need to rethink our approach to overcorrection of hyponatremia. Kidney News, May 2023; 15(5):14–15. https://www.kidneynews.org/view/journals/kidney-news/15/5/article-p14_6.xml
- 2.↑
MacMillan TE, et al. Osmotic demyelination syndrome in patients hospitalized with hyponatremia. NEJM Evid 2023; 2:1–9. https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200215
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Winzeler B, et al. Long-term outcome of profound hyponatremia: A prospective 12 months follow-up study. Eur J Endocrinol 2016; 175:499–507. doi: 10.1530/EJE-16-0500
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Nzerue CM, et al. Predictors of outcome in hospitalized patients with severe hyponatremia. J Natl Med Assoc 2023; 95:335–343. PMID: 12793790
- 5.↑
George JC, et al. Risk factors and outcomes of rapid correction of severe hyponatremia. Clin J Am Soc Nephrol 2018; 13:984–992. doi: 10.2215/CJN.13061117
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Vu T, et al. Patients presenting with severe hypotonic hyponatremia: Etiological factors, assessment, and outcomes. Hosp Pract (1995) 2009; 37:128–136. doi: 10.3810/hp.2009.12.266
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Geoghegan P, et al. Sodium correction practice and clinical outcomes in profound hyponatremia. Mayo Clin Proc 2015; 90:1348–1355. doi: 10.1016/j.mayocp.2015.07.014
- 8.↑
MacMillan TE, Cavalcanti RB. Outcomes in severe hyponatremia treated with and without desmopressin. Am J Med 2018; 131:317.e1–317.e10. doi: 10.1016/j.amjmed.2017.09.048
- 9.↑
Tandukar S, et al. Osmotic demyelination syndrome following correction of hyponatremia by ≤10 mEq/L per day. Kidney360 2021; 2:1415–1423. doi: 10.34067/KID.0004402021
- 10.↑
Rangan GK, et al. Clinical characteristics and outcomes of hyponatraemia associated with oral water intake in adults: A systematic review. BMJ Open 2021; 11:e046539. doi: 10.1136/bmjopen-2020-046539
- 11.↑
Woodfine JD, van Walraven C. Criteria for hyponatremic overcorrection: Systematic review and cohort study of emergently ill patients. J Gen Intern Med 2020; 35:315–321. doi: 10.1007/s11606-019-05286-y
- 12.↑
Lohr JW. Osmotic demyelination syndrome following correction of hyponatremia: Association with hypokalemia. Am J Med 1994; 96:408–413. doi: 10.1016/0002-9343(94)90166-x
- 13.↑
Gabler NB, et al. Mortality among patients admitted to strained intensive care units. Am J Respir Crit Care Med 2013; 188:800–806. doi: 10.1164/rccm.201304-0622OC
- 14.↑
Siddique SM, et al. Interventions to reduce hospital length of stay in high-risk populations: A systematic review. JAMA Netw Open 2021; 4:e2125846. doi: 10.1001/jamanetworkopen.2021.25846
- 15.↑
Kinoshita T, et al. Effects of correction rate for severe hyponatremia in the intensive care unit on patient outcomes. J Crit Care (published online ahead of print May 13, 2023). doi: 10.1016/j.jcrc.2023.154325; https://www.sciencedirect.com/science/article/abs/pii/S0883944123000746?via%3Dihub
