Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis

Giovanni Corona, Corinna Giuliani, Joseph G Verbalis, Gianni Forti, Mario Maggi, Alessandro Peri, Giovanni Corona, Corinna Giuliani, Joseph G Verbalis, Gianni Forti, Mario Maggi, Alessandro Peri

Abstract

Background: Hyponatremia is the most common electrolyte disorder and it is associated with increased morbidity and mortality. However, there is no clear demonstration that the improvement of serum sodium concentration ([Na(+)]) counteracts the increased risk of mortality associated with hyponatremia. Thus, we performed a meta-analysis that included the published studies that addressed the effect of hyponatremia improvement on mortality.

Methods and findings: A Medline, Embase and Cochrane search was performed to retrieve all English-language studies of human subjects published up to June 30th 2014, using the following words: "hyponatremia", "hyponatraemia", "mortality", "morbidity" and "sodium". Fifteen studies satisfied inclusion criteria encompassing a total of 13,816 patients. The identification of relevant abstracts, the selection of studies and the subsequent data extraction were performed independently by two of the authors, and conflicts resolved by a third investigator. Across all fifteen studies, any improvement of hyponatremia was associated with a reduced risk of overall mortality (OR=0.57[0.40-0.81]). The association was even stronger when only those studies (n=8) reporting a threshold for serum [Na(+)] improvement to >130 mmol/L were considered (OR=0.51[0.31-0.86]). The reduced mortality rate persisted at follow-up (OR=0.55[0.36-0.84] at 12 months). Meta-regression analyses showed that the reduced mortality associated with hyponatremia improvement was more evident in older subjects and in those with lower serum [Na(+)] at enrollment.

Conclusions: This meta-analysis documents for the first time that improvement in serum [Na(+)] in hyponatremic patients is associated with a reduction of overall mortality.

Conflict of interest statement

Competing Interests: Joseph G. Verbalis has served as a consultant and member of advisory boards and Speakers’ Bureau for Otsuka and has received research grants from Otsuka; Alessandro Peri has served as a consultant and member of advisory boards for Otsuka. Giovanni Corona, Corinna Giuliani, Gianni Forti and Mario Maggi have nothing to disclose. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Trial flow diagram.
Fig 1. Trial flow diagram.
Fig 2. Funnel plot of the observational…
Fig 2. Funnel plot of the observational studies included in the meta-analysis.
Fig 3. Odds ratio for overall mortality…
Fig 3. Odds ratio for overall mortality rate in patients with any increase of serum [Na+].
Fig 4. Odds ratio for overall mortality…
Fig 4. Odds ratio for overall mortality rate in patients from studies in which a threshold for serum [Na+] improvement >130 mmol/L was reported.

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