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Do Hyponatremia or Its Underlying Mechanisms Associate With Mortality Risk in Observational Data?

ABSTRACT: Objectives:Whether unaccounted determinants of hyponatremia, rather than water excess per se, primarily associate with mortality in observational studies has not been explicitly examined. Design:Retrospective cohort study of the association between hyponatremia and mortality, stratified by outpatient diuretic use in three strata. Setting:An inception cohort of 13,661 critically ill patients from a tertiary medical center. Measurements and Main Results:Admission serum sodium concentrations, obtained within 12 hours of admission to the ICU, were the primary exposure. Hyponatremia was associated with 1.82 (95% CI, 1.56-2.11; p < 0.001) higher odds of mortality, yet differed according to outpatient diuretic use (multiplicative interaction between thiazide and serum sodium < 133 mEq/L; p = 0.002). Although hyponatremia was associated with a three-fold higher (odds ratio, 3.11; 95% CI, 2.32-4.17; p < 0.001) odds of mortality among those prescribed loop diuretics, no increase of risk was observed among thiazide diuretic users (odds ratio, 0.87; 95% CI, 0.47-1.51; p = 0.63). When examined as a continuous variable, each one mEq/L higher serum sodium was associated with 8% (odds ratio, 0.92; 95% CI, 0.90-0.94; p < 0.001) lower odds of mortality in loop diuretic patients and 5% (odds ratio, 0.95; 95% CI, 0.93-0.96, p < 0.001) lower in diuretic naïve patients, but was not associated with mortality risk among thiazide users (odds ratio, 0.99; 95% CI, 0.95-1.02; p = 0.45). Conclusions:Hyponatremia is not uniformly associated with increased mortality, but differs according to diuretic exposure. Our results suggest that the underlying pathophysiologic factors that lead to water excess, rather water excess itself, account in part for the association between hyponatremia and poor outcomes. More accurate estimations about the association between hyponatremia and outcomes might influence clinical decision-making.

SUBMITTER: Danziger J

PROVIDER: S-EPMC7063901 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Do Hyponatremia or Its Underlying Mechanisms Associate With Mortality Risk in Observational Data?

Danziger John J Lee Joon J Mark Roger G RG Celi Leo Anthony LA Mukamal Kenneth J KJ

Critical care explorations 20200129 1

<h4>Objectives</h4>Whether unaccounted determinants of hyponatremia, rather than water excess per se, primarily associate with mortality in observational studies has not been explicitly examined.<h4>Design</h4>Retrospective cohort study of the association between hyponatremia and mortality, stratified by outpatient diuretic use in three strata.<h4>Setting</h4>An inception cohort of 13,661 critically ill patients from a tertiary medical center.<h4>Measurements and main results</h4>Admission serum ...[more]

PMID: 32166294

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Project description:BackgroundHyponatremia 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 findingsAn 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.ConclusionsThis 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.

Project description:BackgroundHyponatremia (serum sodium concentration < 135 mmol/L) is the most common electrolyte abnormality and is a predictor of the mortality of hospitalized patients in Western countries. However, hyponatremia data are lacking in Asian countries. Here we evaluate the epidemiology and mortality of hyponatremia in general medical hospitalized patients in China.MethodsThis is a cohort study of 154,378 adults who were hospitalized between 2008 and 2012 at a teaching hospital in Beijing. We identified hospital patients with hyponatremia and calculated the prevalence and in-hospital mortality of hyponatremia. We also conducted a comprehensive retrospective review of the medical records of patients who had severe hyponatremia (serum sodium <120 mmol/L) during hospitalization in 2012.ResultsThe overall prevalence of hyponatremia at some point during hospitalization was 17.5% (26,990 patients), but only 0.26% (394 patients) of cases were identified with the diagnostic code of hyponatremia. Hyponatremia was more common in patients with infectious disease, cancer, or cardiovascular disease as the primary reason for hospitalization based on discharge diagnosis, with prevalences of 33.0, 25.9 and 24.9%, respectively. The in-hospital mortality was 0.48% amongst patients without hyponatremia compared to 3.57 and 20.23% in patients with serum sodium levels of 130-134 and <120 mmol/L, resulting in multivariable adjusted odds ratios (ORs) of 4.8 (95% CI 4.3-5.4) and 32.9 (95% CI 25.2-42.3), respectively. The mortality risk increased with increasing severity of hyponatremia in all diagnostic groups. After the multivariate adjustment, only the Charlson Comorbidity Index and age were independently associated with death risk (OR 1.36, 95% CI 1.14-1.64 and OR 1.04, 95% CI 1.00-1.09, respectively) in the patients with severe hyponatremia.ConclusionsHyponatremia is highly prevalent among Chinese hospitalized patients and is associated with increased in-hospital mortality risk. Physicians should raise awareness to improve the prognosis of hyponatremia.

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Do Hyponatremia or Its Underlying Mechanisms Associate With Mortality Risk in Observational Data?

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Do Hyponatremia or Its Underlying Mechanisms Associate With Mortality Risk in Observational Data?

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