Hyponatremia Improvement Is Associated with a Reduced Risk of Mortality: Evidence from a Meta-Analysis

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.