title: The Economic Burden of Hyponatremia: Systematic Review and Meta-Analysis.
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.
authors.affiliation: Endocrinology Unit, Maggiore-Bellaria Hospital, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Careggi Hospital, Italy.
authors.forename: Corinna
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Department of Medicine and Geriatrics, Careggi Hospital, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Parenti
authors.affiliation: Department of Drug Sciences, University of Pavia, Italy.
authors.forename: Giorgio L
authors.initials: GL
authors.lastname: Colombo
authors.affiliation: Endocrinology Unit, Maggiore-Bellaria Hospital, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sforza
authors.affiliation: Andrology Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Careggi Hospital, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Careggi Hospital, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Careggi Hospital, Italy. Electronic address: alessandro.peri@unifi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: D006760:Hospitalization / Q000191:economics*; D006801:Humans; D007010:Hyponatremia / Q000191:economics*; D007902:Length of Stay / Q000191:economics; D010359:Patient Readmission / Q000191:economics; D013997:Time Factors
keywords: Costs; Hospitalization; Hyponatremia