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. An extensive Medline, Embase and Cochrane search was performed to retrieve the studies published up to October 1^st 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. 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.

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. A Medline, Embase and Cochrane search was performed to retrieve all English-language studies of human subjects published up to June 30^th 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. This meta-analysis documents for the first time that improvement in serum [Na⁺] in hyponatremic patients is associated with a reduction of overall mortality.

Hyponatremia is a very common electrolyte disorder, especially in the elderly, and is associated with significant morbidity, mortality and disability. In particular, the consequences of acute hyponatremia on the brain may be severe, including permanent disability and death. Also chronic hyponatremia can affect the health status, causing attention deficit, gait instability, increased risk of falls and fractures, and osteoporosis. Furthermore, an overly rapid correction of hyponatremia can be associated with irreversible brain damage, which may be the result of the osmotic demyelination syndrome. This review analyzes the detrimental consequences of acute and chronic hyponatremia and its inappropriate correction on the brain and the underlying physiopathological mechanisms, with a particular attention to the less known in vivo and in vitro effects of chronic hyponatremia.