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Meta-Analysis
. 2013 Dec 18;8(12):e80451.
doi: 10.1371/journal.pone.0080451. eCollection 2013.

Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis

Giovanni Corona  1 , Corinna Giuliani  2 , Gabriele Parenti  2 , Dario Norello  2 , Joseph G Verbalis  3 , Gianni Forti  2 , Mario Maggi  4 , Alessandro Peri  2
Affiliations
Meta-Analysis

Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis

Giovanni Corona et al. PLoS One. .

Abstract

Background: Hyponatremia is the most common electrolyte disorder in clinical practice, and evidence to date indicates that severe hyponatremia is associated with increased morbidity and mortality. The aim of our study was to perform a meta-analysis that included the published studies that compared mortality rates in subjects with or without hyponatremia of any degree.

Methods and findings: An extensive Medline, Embase and Cochrane search was performed to retrieve the studies published up to October 1st 2012, using the following words: "hyponatremia" and "mortality". Eighty-one studies satisfied inclusion criteria encompassing a total of 850222 patients, of whom 17.4% were hyponatremic. 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 81 studies, hyponatremia was significantly associated with an increased risk of overall mortality (RR = 2.60[2.31-2.93]). Hyponatremia was also associated with an increased risk of mortality in patients with myocardial infarction (RR = 2.83[2.23-3.58]), heart failure (RR = 2.47[2.09-2.92]), cirrhosis (RR = 3.34[1.91-5.83]), pulmonary infections (RR = 2.49[1.44-4.30]), mixed diseases (RR = 2.59[1.97-3.40]), and in hospitalized patients (RR = 2.48[2.09-2.95]). A mean difference of serum [Na(+)] of 4.8 mmol/L was found in subjects who died compared to survivors (130.1 ± 5.6 vs 134.9 ± 5.1 mmol/L). A meta-regression analysis showed that the hyponatremia-related risk of overall mortality was inversely correlated with serum [Na(+)]. This association was confirmed in a multiple regression model after adjusting for age, gender, and diabetes mellitus as an associated morbidity.

Conclusions: This meta-analysis shows for the first time that even a moderate serum [Na(+)] decrease is associated with an increased risk of mortality in commonly observed clinical conditions across large numbers of patients.

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Conflict of interest statement

Competing Interests: Joseph G. Verbalis has served as a consultant and member of advisory boards and Speakers' Bureau for Astellas Pharma US, Inc., as a consultant and member of advisory boards for Sanofi-Aventis, and as a consultant for Otsuka; Alessandro Peri has served as a consultant and member of advisory boards for Otsuka. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Giovanni Corona, Corinna Giuliani, Gabriele Parenti, Dario Norello, Gianni Forti and Mario Maggi have nothing to disclose.

Figures

Figure 1
Figure 1. Trial flow diagram.
Figure 2
Figure 2. Odds ratio for overall mortality in patients with or without (no) hyponatremia according to the presence of myocardial infarction (A), heart failure (B), cirrhosis (C), pulmonary infection (D), mixed disease (E), or in hospitalized series of subjects (F).
Figure 3
Figure 3. Weighted differences (with 95% CI) of mean serum [Na+] in dead and alive patients.
Figure 4
Figure 4. Relation between serum [Na+] cut-off definition and overall mortality risk.
See this image and copyright information in PMC

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