Hyponatremia in Guillain-Barré Syndrome.

OBJECTIVES: To evaluate incidence, risk factors, and in-hospital outcomes associated with hyponatremia in patients hospitalized for Guillain-Barré Syndrome (GBS). METHODS: We identified adult patients with GBS in the Nationwide Inpatient Sample (2002-2011). Univariate and multivariable analyses were used. RESULTS: Among 54,778 patients hospitalized for GBS, the incidence of hyponatremia was 11.8% (compared with 4.0% in non-GBS patients) and increased from 6.9% in 2002 to 13.5% in 2011 (P < 0.0001). Risk factors associated with hyponatremia in multivariable analysis included advanced age, deficiency anemia, alcohol abuse, hypertension, and intravenous immunoglobulin (all P < 0.0001). Hyponatremia was associated with prolonged length of stay (16.07 vs. 10.41, days), increased costs (54,001 vs. 34,125, $USD), and mortality (20.5% vs. 11.6%) (all P < 0.0001). In multivariable analysis, hyponatremia was independently associated with adverse discharge disposition (odds ratio: 2.07, 95% confidence interval, 1.91-2.25, P < 0.0001). CONCLUSIONS: Hyponatremia is prevalent in GBS and is detrimental to patient-centered outcomes and health care costs. Sodium levels should be carefully monitored in high-risk patients.

The Economic Burden of Hyponatremia: Systematic Review and Meta-Analysis.

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.

The burden of illness in patients with hyponatraemia in Sweden: a population-based registry study.

BACKGROUND: Hyponatraemia (HN; serum sodium level < 135 mmol/l) is the most common electrolyte disturbance seen in clinical practice, and is associated with varying spectrum of symptoms. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common aetiology in hospitalised patients, and can be caused by several different underlying conditions. AIMS: The objectives of this study were to retrospectively examine the baseline characteristics, clinical outcomes and hospital resource utilisation of patients with HN and/or SIADH in Sweden over a 10-year period from 2001 to 2011. Additional analysis was performed on subpopulations of patients with hip fracture, pneumonia and small cell lung cancer (SCLC) to see if trends in outcomes were consistent across a broad range of aetiologies commonly associated with the condition. METHODS: Patient information was taken from the Swedish National Patient Registry, the Swedish Cancer Registry, the Swedish Cause of Death Register and the Swedish Prescribed Drug Register. A total of 34,537 patients (4.38%) were identified with HN and/or SIADH, with the incidence and prevalence rising over the 10-year study period. RESULTS: Of the 34,537 patients identified, 841 had hip fracture, 2635 had pneumonia and 106 had SCLC. Compared with matched control patients, those with HN and/or SIADH had a longer length of hospital stay, a higher re-admission rate and a shorter time to re-admission. CONCLUSIONS: This study showed that HN and/or SIADH negatively impact patient outcomes and healthcare resources related to hospital stay irrespective of the underlying cause. The impact of HN is not confined to the initial hospitalisation, as re-admission rates are also affected.

Prevalence, Timing, Causes, and Outcomes of Hyponatremia in Hospitalized Orthopaedic Surgery Patients.

BACKGROUND: Hyponatremia is common among orthopaedic patients and is associated with adverse clinical outcomes. We examined the prevalence, timing, causes, and outcomes of hyponatremia in adult hospitalized orthopaedic surgery patients. METHODS: We evaluated the medical records of 1067 consecutive orthopaedic surgery patients admitted to a tertiary academic institution. The medical records were reviewed to investigate hyponatremia (serum sodium <135 mEq/L) that (1) had been present on hospital admission or (2) had developed postoperatively. The primary outcomes were the prevalence and timing of, and risk factors for, presentation with or development of hyponatremia. Secondary outcomes were hospital length of stay, total hospital cost, and discharge disposition. Multivariable logistic regression models were used to assess the variables associated with hyponatremia and the effects of hyponatremia on clinical outcomes. RESULTS: Of the 1067 patients, seventy-one (7%) had preoperative hyponatremia and 319 (30%) developed hyponatremia postoperatively. Of the latter, 298 (93%) developed hyponatremia within forty-eight hours postoperatively. Compared with patients with normonatremia, those who presented with hyponatremia, on the average, were older (67.2 versus 60.5 years, p < 0.001), had longer hospital stays (4.6 versus 3.3 days, p < 0.001), incurred higher hospital costs ($19,200 versus $17,000, p = 0.006), and were more likely to be discharged to an extended-care facility (odds ratio [OR] = 2.87, p < 0.001). Developing hyponatremia postoperatively resulted, on average, in a longer hospital stay (3.7 versus 3.3 days, p = 0.002) and greater hospital cost ($18,800 versus $17,000, p < 0.001). Age (OR = 1.13 per decade, p = 0.012), spine surgery (OR = 2.76 versus knee, p < 0.001), hip surgery (OR = 1.76 versus knee, p < 0.001), and the amount of lactated Ringer solution used (OR = 1.16, p = 0.002) increased the risk of developing hyponatremia. CONCLUSIONS: Hyponatremia in orthopaedic patients is associated with longer, costlier hospitalizations. The factors that significantly increased the risk of developing postoperative hyponatremia were an older age, spine fusion, hip arthroplasty, and the amount of lactated Ringer solution used.

Cost-effectiveness of tolvaptan for euvolemic or hypervolemic hyponatremia.

PURPOSE: Tolvaptan is clinically effective in increasing serum sodium concentrations for patients with euvolemic or hypervolemic hyponatremia. Appropriate treatment of hyponatremia may reduce the risk of death, hospital resource utilization, and economic burden. The aim of this study was to estimate the cost-effectiveness of tolvaptan treatment in patients who need to be hospitalized for treatment and monitoring of euvolemic or hypervolemic hyponatremia. METHODS: A decision-analytic model was constructed to assess the clinical and economic impact of tolvaptan compared with placebo during a 1-month treatment period. The probabilities, utility weights, resource utilization, and costs in the model were derived from clinical trials, survey research, and the Korean National Health Insurance database. Cost analysis was performed from the perspective of the South Korean health care setting in 2012 Korean won (KRW). The model outcome was the incremental cost per quality-adjusted life-year gained. In addition, subgroup analysis was performed to identify the cost-effectiveness in case of tolvaptan treatment only for patients with marked hyponatremia. Deterministic and probabilistic sensitivity analyses were performed on key model parameters and assumptions. FINDINGS: The total cost per patient was KRW 1,826,771 for tolvaptan treatment and KRW 2,281,926 for placebo. The quality-adjusted life-years for treatment with and without tolvaptan were 0.0481 and 0.0446, respectively. The base-case analysis revealed that tolvaptan was a more effective and less expensive strategy compared with placebo. In the subgroup analysis, this trend was more apparent in case of tolvaptan treatment only for patients with marked hyponatremia. The robustness of the results was confirmed by using deterministic and probabilistic sensitivity analyses. IMPLICATIONS: This cost-effectiveness analysis found that the use of tolvaptan was less expensive and more effective than treatment without tolvaptan in patients with euvolemic or hypervolemic hyponatremia.

Low prevalence of hyponatremia codification in departments of internal medicine and its prognostic implications.

OBJECTIVE: Hyponatremia is the most frequent ionic disorder among ambulatory and hospitalized populations. The aim of the study is to describe the profile of patients admitted to internal medicine departments of Spanish hospitals with a diagnostic codification of hyponatremia in their discharge sheets. METHODS: Data from the Minimum Basic Data Set (MBDS) of discharged patients from all departments of internal medicine (IM) of the Spanish National Health System (NHS) between 2007 and 2010 were analyzed to describe the profile of patients with diagnostic codification of hyponatremia. RESULTS: A total of 2,134,363 admittances were analyzed, identifying 31,933 (1.5%) with a diagnostic code of hyponatremia (18.3% as principal diagnosis and 81.7% as secondary diagnosis). Mortality among patients with codified hyponatremia was markedly higher than in patients without this condition (13.1% vs 9.8% [OR 1.38; 95% CI 1.33-1.41]). Hyponatremia codification was independently associated with a higher risk of readmission (OR 1.33 CI 95% 1.29-1.38). Average length of stay for patients with hyponatremia was 11.67 days (SD 13.01), compared to 9.84 days (SD 11.61) among the general population admitted to IM (p < 0.001). Mean cost per admission in the presence of codified hyponatremia was €4023 (SD €2531), compared to €3537 (SD €2858.02); p < 0.001. Hyponatremia was more prevalent among patients with the following conditions: dementia, chronic and acute renal failure, hepatic cirrhosis, pressure ulcers, heart failure, and depression. CONCLUSIONS: We found an extremely low prevalence of hyponatremia codification in our series (1.5%). Hyponatremia is underreported and undertreated although numerous studies have shown its devastating impact on hospital admittance. The first step in order to improve this situation is to raise awareness among physicians about a problem that despite its high prevalence is still overlooked.

Health care utilization, costs, and readmission rates associated with hyponatremia.

PURPOSE: Hyponatremia is associated with higher morbidity and mortality rates among hospitalized patients. Our study evaluated health care utilization and associated costs of patients hospitalized with a primary diagnosis of hyponatremia. METHODS: Hospitalized patients with a primary discharge diagnosis of hyponatremia (aged ≥ 18 years) were identified from the Premier Perspective™ database (January 1, 2007-March 31, 2010) and matched to non-hyponatremic (non-HN) patients using a combination of exact patient characteristic matching and propensity score matching. Univariate and multivariate statistics were used to compare hospital resource usage, costs, and 30-day readmission rates between cohorts. RESULTS: Hospital length of stay (LOS) (± standard deviation) (3.78 ± 3.19 vs 3.54 ± 3.26 days; P < 0.001) and cost ($5396 ± $6500 vs $4979 ± $6152; P < 0.001 for the hyponatremic [HN] and non-HN patient cohorts, respectively) were greater for the HN cohort, but intensive care unit (ICU) costs ($3554 ± $6463 vs $3484 ± $8510; P = 0.828) and ICU LOS (2.37 ± 3.47 vs 2.52 ± 3.87; P = 0.345) did not differ between cohorts. The ICU admission rate (7.9% vs 4.4%; P < 0.001), as well as the 30-day readmission rate (12.1% vs 2.9%; P < 0.001) were greater for the HN cohort. After adjustment for key patient characteristics, hyponatremia was associated with a 7.6% increase in hospital LOS, an 8.9% increase in hospital costs, and a 9% increase in ICU costs. Hyponatremia was associated with an increased risk of ICU admission (odds ratio, 1.89, confidence limits, 1.72, 2.07; P < 0.001) and 30-day hospital readmission for hyponatremia (odds ratio, 4.76; confidence limits, 4.31, 5.26; P < 0.001). CONCLUSION: Compared with non-HN patients, patients with a primary diagnosis of hyponatremia use a greater amount of hospital resources and represent a challenge to hospital profitability due to the increased likelihood of 30-day readmission.

The frequency, cost, and clinical outcomes of hypernatremia in patients hospitalized to a comprehensive cancer center.

PURPOSE: To study the frequency of hypernatremia in hospitalized cancer patients and its impact on clinical outcomes and healthcare cost. METHODS: Cross-sectional analysis of data obtained from patients admitted to the University of Texas M. D. Anderson Cancer Center over a 3-month period in 2006. The clinical outcomes and hospital costs were compared among hypernatremics, eunatremics, and hyponatremics (serum sodium values include >147, 135-147, and <135 mEq/L, respectively). RESULTS: Of 3,446 patients with at least one serum sodium value, 51.4 % were eunatremic, 46.0 % hyponatremic, and 2.6 % hypernatremic with most of the hypernatremia (90 %) acquired during hospital stay. The multivariate hazard ratio (HR) for mortality in hypernatremic was 5-fold higher than eunatremic (HR for 90 days-5.09 (95 % CI, 3.32-7.81); p < 0·01) and over 2-fold higher than hyponatremic (HR for 90 days-2.79 (95 % CI, 1.91-4.11), p < 0.01). The length of hospital stay in hypernatremic was 2-fold higher than in hyponatremic and 4-fold higher than in eunatremic (e.g., 27 ± 22 days in hypernatremic vs. 6 ± 5 days in eunatremic; mean ± SD, p < 0.01). The hospital bill was higher for hypernatremic compared with the rest of the groups (46 % over eunatremic and 37 % over hyponatremic, p < 0.01 for both). CONCLUSIONS: Although hypernatremia was far less frequent than hyponatremia in the hospitalized cancer patients, most hypernatremia were acquired in the hospital and had substantially higher mortality, hospital stay, and hospital bills than eunatremic or even hyponatremic patients. Studies are warranted to determine whether avoidance of hypernatremia or its prompt and sustained correction improves clinical outcomes.

Hyponatremia-associated healthcare burden among US patients hospitalized for cirrhosis.

INTRODUCTION: Hyponatremia is a frequent comorbid condition of patients hospitalized for cirrhosis and a predictor of disease severity and mortality. This study evaluated the healthcare burden of hyponatremia among patients hospitalized for cirrhosis in the real world. METHODS: Hyponatremic (HN) patients (>-18 years of age) with cirrhosis were identified using the Premier Hospital Database (January 1, 2007 to March 31, 2010) and matched to non-HN patients with cirrhosis using a combination of exact patient characteristics and propensity score matching. Univariate and multivariate statistics were utilized to compare hospital resource utilization, cost, and 30-day hospital re-admission among patient cohorts. RESULTS: The study population included 21,864 subjects (HN 10,932; non-HN 10,932). The hospital length of stay (LOS) (7.63 ± 7.4 vs. 5.89 ± 6.2 days; P < 0.001), hospital cost ($13,842 ± $20,702 vs. $11,140 ± $20,562; P < 0.001), intensive care unit (ICU) LOS (4.58 ± 4.7 vs. 3.59 ± 4.4 days; P < 0.001), and ICU cost ($7,038 ± $7,781 vs. $5,360 ± $7,557; P < 0.001) were greater for the HN cohort, as was the 30-day re-admission rate (all cause: 31.1% vs. 24.8%; P < 0.001; hyponatremia related: 25.1% vs. 11.0%; P < 0.001). Multivariate analysis showed that hyponatremia was associated with a 29.5% increase in hospital LOS, a 26.6% increase in overall hospital cost, a 23.2% increase in S. ICU LOS, and a 28.6% increase in ICU cost. Additionally, hyponatremia was associated with an increased risk of 30-day hospital re-admission (all cause: odds ratio [OR] 1.37; confidence interval [CI] 1.28-1.46; P < 0.001; hyponatremia related: OR 2.68; CI 2.48-2.90; P < 0.001). CONCLUSION: Hyponatremia in patients with cirrhosis is a predictor of increased hospital resource use and 30-day hospital re-admission, and represents a potential target for intervention to reduce healthcare expenditures for patients hospitalized for cirrhosis.

Healthcare resource burden associated with hyponatremia among patients hospitalized for heart failure in the US.

OBJECTIVE: To evaluate the burden of hyponatremia in terms of hospital resource utilization, costs, and 30-day hospital readmission among patients hospitalized for heart failure (HF) in routine clinical practice. METHODS: Hyponatremic (HN) patients (≥18 years of age) with HF discharged between January 2, 2007 and March 31, 2010 were selected from the Premier Hospital Database and matched to non-HN HF patients using exact and propensity score matching. Univariate and multivariate statistics were utilized to compare hospital resource utilization (total and intensive care unit (ICU)) and associated costs and 30-day hospital readmission among cohorts. RESULTS: The study population included 51,710 subjects (HN = 25,855, non-HN = 25,855). In comparison to the non-HN cohort, length of stay (LOS) (7.7 ± 8.3 vs 6.3 ± 7.6 days, p < 0.001), hospitalization cost ($13,339 ± $19,273 vs $10,475 ± 15,157, p < 0.001), ICU LOS (4.9 ± 5.4 vs 4.2 ± 5.4 days, p < 0.001) and ICU cost ($7195 ± $9522 vs $5618 ± 10,919, p < 0.001) as well as rate of 30-day readmission (all cause: 25.3% vs 22.2%, p < 0.001; hyponatremia-related: 21.4% vs 5.0%, p < 0.001) were greater for the HN cohort. After adjustment, hyponatremia was associated with a 21.5% increase in hospital LOS, a 25.6% increase in hospital cost, a 13.7% increase in ICU LOS and a 24.6% increase in ICU cost. Additionally, hyponatremia was associated with increased risk of ICU admission (Odds Ratio (OR) = 1.58, [CI = 1.37, 1.84], p < 0.001) and 30-day hospital readmission (all cause: OR = 1.19, [CI = 1.14, 1.24], p < 0.001; hyponatremia-related: 5.10 [CI = 4.77, 5.46], p < 0.001). LIMITATIONS: Laboratory data for serum sodium level are not available in the Premier database and the severity of hyponatremia could not be established, although several patient variables were controlled for in this study by exact and propensity score matching techniques. CONCLUSIONS: Hyponatremia in HF patients is a predictor of increased hospital resource use and represents a potential target for intervention to reduce healthcare expenditures.

Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients: a single-center experience in Turkey.

PURPOSE: Hyponatremia is a common electrolyte disorder in hospitalized patients. Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients are not well known. METHODS: Elderly (>64 years) patients admitted to the emergency department (ED) and hospitalized between January 1, 2010, and December 31, 2010, were evaluated. Hyponatremia was defined as serum sodium level below 135 mmol/L. Hyponatremic patients were divided into two groups: group 1 (n = 150, 65-74 years old) and group 2 (n = 103, >74 years old). RESULTS: A total of 4,960 patients above 65 years of age admitted to ED and hospitalized were included. Prevalence of ED in group 1 and group 2 was 4.1 % (150/3,651) and 7.8 % (103/1,309), respectively (p < 0.001). Vomiting and diarrhea were the most important complaints. A total of 111 (43.8 %) patients were being treated with renin-angiotensin system (RAS) blockers. Mortality, morbidity and hospital cost increased in parallel to decrease in serum Na(+) level and increase in age. Group 2 subjects had not only higher intensive care need (p < 0.01) and mortality rates (p < 0.01), but also higher hospital cost burden (p < 0.05) compared to group 1. Alzheimer's disease was one of the most common co-morbidity in patients, particularly in group 2 (5.3 % vs. 21.3 %, p < 0.001). CONCLUSION: Hyponatremia-associated hospitalization is an important and potentially lethal condition in elderly and very elderly patients. Clinicians should be careful when prescribing RAS blockers and diuretics in elderly patients.

Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US.

BACKGROUND: Hyponatremia is a prevalent electrolyte disorder in hospitalized patients indicative of greater morbidity and mortality. A large-scale retrospective analysis was conducted to evaluate the incremental burden of hospitalized hyponatremic (HN) versus non-HN patients in terms of hospital resource utilization, costs, and hospital readmissions in the real-world setting. METHODS: HN patients (≥18 years) were selected from the Premier Hospital Database between January 1, 2007 and March 31, 2010 and matched to a non-HN control cohort using propensity score matching. Bivariate and multivariate statistics were employed to evaluate the differences in healthcare resource utilization, costs, and hospital readmissions between patient cohorts. RESULTS: Among the matched patient cohorts, length of stay (LOS) (8.8 ± 10.3 vs 7.7 ± 8.5 days, P < 0.001), hospital admission costs ($15,281 ± $24,054 vs $13,439 ± $22,198, P < 0.001), intensive care unit (ICU) LOS (5.5 ± 7.9 vs 4.9 ± 7.1 days, P < 0.001), and ICU costs ($8525 ± $13,342 vs $7597 ± $12,695, P < 0.001) were greater for the HN versus non-HN cohort, as were hospital readmission rates 30 days postdischarge. Multivariate regressions further demonstrated that hyponatremia was associated with an increase of 10.9% for LOS, 8.2% for total hospitalization costs, 10.2% for ICU LOS, and 8.9% for ICU costs. Additionally, after multivariate adjustment, hyponatremia was associated with a 15.0% increased chance for hospital readmission 30 days postdischarge (P < 0.0001). CONCLUSIONS: Hyponatremia is an independent predictor of increased hospitalization LOS and cost, ICU admission and cost, and 30-day hospital readmission, and therefore represents a potential target for intervention to reduce healthcare expenditures for a large population of hospitalized hyponatremic patients.

Hyponatremia with intracranial malignant tumor resection in children.

OBJECT: Intracranial neoplasms are the second most common childhood cancer, and lead to significant morbidity and mortality. Hyponatremia is a complication associated with neurosurgical procedures, but children undergoing intracranial tumor resection have not been selectively studied. In this study, the authors aimed to determine the incidence and risk factors associated with hyponatremia among children undergoing intracranial neoplasm resection. METHODS: A retrospective cohort was compiled using the 2006 Kids' Inpatient Database to identify children younger than 21 years of age who underwent intracranial neoplasm resection. Hyponatremia was ascertained by diagnosis codes. Bivariate analyses were conducted using chi-square and Mann-Whitney U-tests. Logistic regression models were developed to evaluate factors associated with hyponatremia in bivariate analyses. RESULTS: Hyponatremia occurred in 205 (8.7%) of 2343 annual weighted cases, and was independently associated with tumor location in the deep brain structures and ventricles compared with the cortical area (adjusted odds ratio [aOR] 2.4; 95% CI 1.1-5.3). Hyponatremia was also associated with obstructive hydrocephalus (aOR 2.7; 95% CI 1.7-4.3) and emergency department admission (aOR 1.7; 95% CI 1.1-2.4). Hyponatremia was significantly associated with mechanical ventilation, ventriculostomy placement, ventriculoperitoneal shunt placement, and sepsis. Hyponatremia was also associated with a significantly longer average length of stay (24.6 vs 10.2 days), higher average charges ($191,000 vs $92,000), and a higher percentage of discharges to intermediate-care facilities. CONCLUSIONS: Hyponatremia commonly occurs with resection of intracranial malignant tumors, especially for lesions located in the deep brain and in patients with obstructive hydrocephalus. Hyponatremia was associated with higher morbidity. Further research is needed to develop targeted monitoring and intervention strategies to decrease perioperative hyponatremia and to determine if this could decrease the number of complications in this specialized population.

Evaluation of costs associated with tolvaptan-mediated hospital length of stay reduction among US patients with the syndrome of inappropriate antidiuretic hormone secretion, based on SALT-1 and SALT-2 trials.

BACKGROUND: Two randomized clinical trials, the Study of Ascending Levels of Tolvaptan in Hyponatremia 1 and 2 (SALT-1 and SALT-2), showed that tolvaptan was an efficacious and safe therapy for the treatment of hyponatremic patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). HYPOTHESIS: This study evaluated the potential cost savings associated with tolvaptan usage based on the SALT-1 and SALT-2 trials. METHODS: Hospital length of stay (LOS) reduction associated with tolvaptan versus placebo was evaluated among hyponatremic patients with the SIADH (serum sodium < 135 mEq/L) from the combined data of the SALT-1 and SALT-2 trials. The Healthcare Cost and Utilization Project 2009 Nationwide Inpatient Sample database was used to estimate hospital cost and LOS for hospitalizations of adult (age ≥ 18 years) patients with the SIADH. A cost-offset model was constructed to evaluate the impact of tolvaptan on hospital cost and LOS, with univariate and multivariate Monte Carlo sensitivity analyses. RESULTS: In the SALT-1 and SALT-2 trials, patients with the SIADH receiving tolvaptan had a shorter hospital LOS than patients receiving placebo (4.98 vs 6.19 days, respectively). There were 21 718 hospitalizations for the SIADH identified from the Healthcare Cost and Utilization Project Nationwide 2009 Inpatient Sample database, with a mean LOS of 5.7 days and mean total hospital costs of $8667. Using an inpatient tolvaptan treatment duration of 4 days, with a daily wholesale acquisition cost of $250, the cost-offset model estimated an LOS reduction among SIADH hospitalizations of 1.11 days. The total cost offset, including tolvaptan drug cost, was estimated to be $694 per admission. The cost-neutral break-even duration of tolvaptan therapy is 6.78 days. Univariate and multivariate sensitivity analyses demonstrated consistent cost reduction associated with tolvaptan usage. Ten thousand cycles of Monte Carlo simulation showed the 95% CI for cost offset to be $73 to $1405. CONCLUSION: Based on the SALT-1 and SALT-2 trials, tolvaptan usage is associated with a shorter hospital LOS than placebo among patients with the SIADH. Including the drug cost for 4 days of inpatient tolvaptan therapy, tolvaptan is associated with an estimated mean hospital cost reduction of $694 per admission in the United States.

The impact of hyponatremia.

Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with significant morbidity and mortality. Clinical consequences of hyponatremia include neurologic dysfunction, decreased mental function, cerebral edema, gait disturbances and falls, osteoporosis, and fractures. Hyponatremia can increase hospital length of stay by 1-2 days and correlates with an increased risk of intensive care unit admission. Thus, hyponatremia is associated with substantial economic and clinical consequences, as well as an increased risk of mortality, especially in individuals with very low serum sodium concentrations.

Cost and resource allocation issues in managing hyponatremia: the pharmacist's role.

Hyponatremia is associated with significant morbidity and mortality in a wide variety of patients with underlying disease states. Hospital-associated hyponatremia is a common occurrence, and all forms of hyponatremia are independently associated with heightened resource consumption during hospitalization as well as after discharge to both short-term and long-term care facilities. The chronic morbidities of hyponatremia, even when not severe, can have a significant impact on health care costs. Resolving hyponatremia during hospitalization decreases the risk of mortality conferred by the disorder. Patients at risk for hyponatremia may not receive adequate investigation into cause of hyponatremia; thus, increased awareness may result in better identification of patients at risk, and more aggressive monitoring in both the inpatient and outpatient settings may lead to appropriate intervention. In the management of hyponatremia, clinical pharmacists have a key role in identifying the source of the hyponatremia, carefully monitoring serum sodium concentration and symptoms of hyponatremia, and intervening with appropriate therapy including avoidance of interventions that may exacerbate hyponatremia.

Dyshomeostasis of serum sodium concentration in congestive heart failure.

Congestive heart failure (CHF) is the most common discharge diagnosis in the United States and accounts for greater than 1 million hospital discharges annually. CHF is associated with many serum electrolyte abnormalities, the most common and perhaps most significant of which is hyponatremia. CHF with hyponatremia makes the already high morbidity and mortality of CHF even more unfavorable. Further, the usual treatment for CHF with diuretics usually aggravates hyponatremia. Hyponatremia may result in impaired cognition and neurologic performance in a large number of patients, which is usually reversible with correction. The high morbidity and mortality with CHF and hyponatremia are not improved with the usual treatment with diuretics or ultrafiltration. This article provides an overview of the pathophysiology of hyponatremia in CHF. In addition, the authors will explore the various treatment options that are available and the evidence to support their utility.

Economic impact of hyponatremia in hospitalized patients: a retrospective cohort study.

BACKGROUND: Hyponatremia is the most common electrolyte abnormality seen in general hospital patients, with an incidence of 1% to 6% in the United States. OBJECTIVE: We aimed to evaluate the impact of varying levels of hyponatremia at admission on length of stay (LOS) and cost of care in adult hospitalized patients. METHODS: A retrospective cohort study was conducted using an existing clinical database from a large academic-setting hospital. All adult admissions from January 2004 through May 2005 with serum sodium level at admission of < or = 134 mEq/L were separated into 2 cohorts: patients with moderate-to-severe hyponatremia (serum sodium level at admission of < or = 129 mEq/L, n = 547) and patients with mild-to-moderate hyponatremia (serum sodium level of 130-134 mEq/L, n = 1500). ICD-9 diagnosis codes for these 2047 admissions with hyponatremia were used to identify a cohort of 7573 admissions with the same principal admitting diagnoses and a serum sodium level of 135 to 145 mEq/L. Differences in hospital LOS, intensive care unit (ICU) admission rate, and median total costs per admission between cohorts were examined using multiple linear regression, logistic, and quantile regression models. RESULTS: Admissions with hyponatremia had significantly longer hospital LOS than those admitted without hyponatremia (median LOS: moderate-to-severe hyponatremia, 8 days; mild-to-moderate hyponatremia, 8 days; normal, 6 days; P < 0.001). Patients with more severe hyponatremia were also more likely to be admitted to the ICU during the hospital stay (moderate-to-severe hyponatremia, 32%; mild-to-moderate hyponatremia, 26%; normal, 22%; P < 0.001). These trends were also reflected in the total costs per admission, with median costs of $16,606 for moderate-to-severe hyponatremia cases, $14,266 for mild-to-moderate hyponatremia cases, and $13,066 for normal admissions (P < 0.001). CONCLUSIONS: Hyponatremia at admission was associated with increased LOS and cost of care for hospitalized patients. Interventions or pharmacotherapies for the prompt treatment of hyponatremia could potentially reduce morbidity and LOS, thereby reducing the utilization of health care resources.

Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients.

BACKGROUND: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na(+)]<135 mEq/L. RESULTS: The incidence of hyponatremia at admission was 5.5% (n=10,899). Patients with hyponatremia were older (65.7+/-19.6 vs. 61.5+/-21.8, p<0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8+/-2.1 vs. 1.3+/-1.8, p<0.001) than those with normal [Na(+)]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3% vs. 10.9%, p<0.001) and mechanical ventilation (MV) (5.0% vs. 2.8%, p<0.001) within 48 hours of hospitalization. Hospital mortality (5.9% vs. 3.0%, p<0.001), mean length of stay (HLOS, 8.6+/-8.0 vs. 7.2+/-8.2 days, p<0.001) and costs ($16,502+/-$28,984 vs. $13,558+/-$24,640, p<0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95% CI 1.56-1.73) and MV (OR 1.68, 95% CI 1.53-1.84), and higher hospital mortality (OR 1.55, 95% CI 1.42-1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289. CONCLUSIONS: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55% increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na(+)] may impact these outcomes.