Clinical research study
The Economic Burden of Hyponatremia: Systematic Review and Meta-Analysis

https://doi.org/10.1016/j.amjmed.2016.03.007Get rights and content

Abstract

Background

Hyponatremia is the most common electrolyte abnormality observed in clinical practice. Several studies have demonstrated that hyponatremia is associated with an increased length of hospital stay and of hospital resource utilization. To clarify the impact of hyponatremia on the length of hospitalization and costs, we performed a meta-analysis based on published studies that compared hospital length of stay and cost between patients with and without hyponatremia.

Methods

An extensive Medline, Embase, and Cochrane search was performed to retrieve all studies published up to April 1, 2015 using the following words: “hyponatremia” or “hyponatraemia” AND “hospitalization” or “hospitalisation.” A meta-analysis was performed including all studies comparing duration of hospitalization and hospital readmission rate in subjects with and without hyponatremia.

Results

Of 444 retrieved articles, 46 studies satisfied the inclusion criteria, encompassing a total of 3,940,042 patients; among these, 757,763 (19.2%) were hyponatremic. Across all studies, hyponatremia was associated with a significantly longer duration of hospitalization (3.30 [2.90-3.71; 95% CIs] mean days; P < .000). Similar results were obtained when patients with associated morbidities were analyzed separately. Furthermore, hyponatremic patients had a higher risk of readmission after the first hospitalization (odds ratio 1.32 [1.18-1.48; 95% CIs]; P < .000). A meta-regression analysis showed that the hyponatremia-related length of hospital stay was higher in males (Slope = 0.09 [0.05-0.12; 95% CIs]; P = .000 and Intercept = −1.36 [−3.03-0.32; 95% CIs]; P = .11) and in elderly patients (Slope = 0.002 [0.001-0.003; 95% CIs]; P < .000 and Intercept = 0.89 [0.83-0.97; 95% CIs]; P < .001). A negative association between serum [Na+] cutoff and duration of hospitalization was detected. No association between duration of hospitalization, serum [Na+], and associated morbidities was observed. Finally, when only US studies (n = 8) were considered, hyponatremia was associated with up to around $3000 higher hospital costs/patient when compared with the cost of normonatremic subjects.

Conclusions

This meta-analysis confirms that hyponatremia is associated with a prolonged hospital length of stay and higher risk of readmission. These observations suggest that hyponatremia may represent one important determinant of the hospitalization costs.

Section snippets

Methods

This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist (see Appendix 1, available online) (http://www.prisma-statement.org/).

Results

Of 444 retrieved articles, 358 were excluded for different reasons. The flow of the meta-analysis is summarized in Figure 1, and the characteristics of the studies included in the meta-analysis are summarized in Table 1 (see references3, 10, 17, 19, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62). Eighty-six full-text articles were considered potentially eligible for the

Discussion

The present meta-analysis, which derives from the study of a large number of patients, confirms that hyponatremia represents a frequent condition observed in up to 20% of hospitalized patients. In addition, our data suggest that hyponatremia is associated with a prolonged hospital length of stay, and higher risk of readmission. The data were similar when European studies were compared with those performed in North America. Length of hospital stay is a strong determinant of the cost of hospital

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    Funding: None.

    Conflict of Interest: AP has served as a consultant and member of advisory boards for Otsuka. GLC has served as a consultant on advisory boards for Astellas, LEO Pharma, Sanofi, Merck Sharp and Dohme, DOC Generici, Takeda, UCB Pharma, and MerckSerono, and has received research and educational grants from Bayer HealthCare, Takeda, Gilead Sciences, Merck Sharp and Dohme, Otsuka and LEO Pharma. The authors report no other conflicts of interest in this work.

    Authorship: All authors had access to the data. Study concept and design: GC; Acquisition of data: CG, GP; Analysis and interpretation of data: GC, AP, GLC; Drafting of the manuscript: GC, AP, CG; Critical revision of the manuscript for important intellectual content: GF, MM, AS, GLC; Statistical analysis: GC; Study supervision: AP.

    1

    These authors contributed equally to this article.

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