Cost of illness of hyponatremia in the United States

BACKGROUND: Hyponatremia is a disorder of fluid and electrolyte balance characterized by a relative excess of body water relative to body sodium content. It is the most common electrolyte disorder encountered in clinical medicine and is associated with negative outcomes in many chronic diseases. However, there is limited information in the literature about health care resource use and costs attributable to the effects of the condition. The purpose of this analysis was to estimate the annual cost of illness of hyponatremia in the United States. METHODS: The study utilized a prevalence-based cost of illness framework that incorporated data from publicly available databases, published literature and a consensus panel of expert physicians. Panel members provided information on: classification of hyponatremia patients, treatment settings for hyponatremia (i.e., hospital, emergency room, doctor's office), and health care resource use associated with the diagnosis and treatment of hyponatremia. Low and high prevalence scenarios were estimated and utilized in a spreadsheet-based cost of illness model. Costs were assigned to units of resources and summarized across treatment settings. RESULTS: The prevalence estimate for hyponatremia ranged from 3.2 million to 6.1 million persons in the U.S. on an annual basis. Approximately 1% of patients were classified as having acute and symptomatic hyponatremia, 4% acute and asymptomatic, 15%–20% chronic and symptomatic, and 75–80% chronic and asymptomatic. Of patients treated for hyponatremia, 55%–63% are initially treated as inpatients, 25% are initially treated in the emergency room, and 13%–20% are treated solely in the office setting. The direct costs of treating hyponatremia in the U.S. on an annual basis were estimated to range between $1.6 billion and$3.6 billion. CONCLUSION: Treatment of hyponatremia represents a significant healthcare burden in the U.S. Newer therapies that may reduce the burden of hyponatremia in the inpatient setting could minimize the costs associated with this condition

V2 Receptor Antagonist; Tolvaptan

Hyponatremia is the most common electrolyte disorder in hospitalized patients. Many studies documented that it was related to increased morbidity and mortality in patients with congestive heart failure, liver cirrhosis, and neurologic diseases. Although knowledge of hyponatremia has been cumulated, the optimal management of hyponatremia remains incompletely established in clinical practice because of the diversity of underlying disease states, and its multiple causes with differing pathophysiologic mechanisms. Since vasopressin receptor antagonists have unique aquaretic effect to selectively increase electrolytes-free water excretion, clinicians could apply a more effective method to treat hyponatremia. Tolvaptan has significant evidence that it improves serum sodium levels in patients with euvolemic or hypervolemic hyponatremia related with heart failure, cirrhosis or syndrome of inappropriate anti-diuretic hormone. Tolvaptan has acceptable safety and tolerability for long-term usage in chronic hyponatremia, and the beneficial effects on serum Na+ occurred in patients with both mild and marked hyponatremia

Hyponatremia-Induced Osteoporosis

There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (µCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score –2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03–7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia. © 2010 American Society for Bone and Mineral Research

MDL 17,043 therapy in severe congestive heart failure: Characterization of the early and late hemodynamic, pharmacokinetic, hormonal and clinical response

MDL 17,043, an agent with both inotropic and vasodilator properties, was evaluated in the treatment of chronic severe heart failure. The early and late hemodynamic, hormonal, pharmacokinetic and clinical responses to oral MDL 17,043 were studied in 20 patients. MDL 17,043 acutely increased cardiac output from 3.6 ± 0.9 to 4.6 ± 1.0 liters/min ( + 28%, p < 0.001) and decreased mean pulmonary artery wedge pressure from 24 ± 8 to 13 ± 8 mm Hg (−46%, p < 0.001), mean right atrial pressure from 10 ± 5 to 4 ± 4 mm Hg (−60%, p < 0.001) and mean arterial pressure from 78 ± 9 to 70 ± 11 mm Hg (−10%, p < 0.001). Hemodynamic improvement was sustained for 8 hours. Plasma renin activity tended to increase (0.10 < p > 0.05), plasma norepinephrine tended to decrease (0.10 < p > 0.05) and arginine vasopressin did not show any directional change. Elimination half-life for MDL 17,043 was approximately 20 hours.Hemodynamic responsiveness was maintained in six patients undergoing restudy at 4 weeks. Initial subjective improvement in the 20 patients occurred in 90%, was present at 4 weeks in 50% and continued longer than 3 months in 25%. Side effects occurred in 75% and required cessation of treatment in 10%. Thirteen (93%) of 14 patients on long-term therapy died (median time after start of MDL 17,043 therapy 39 days). Deaths were sudden in 69%.It is concluded that oral MDL 17,043 produces early and late hemodynamic improvement in patients with severe heart failure. The clinical response suggests caution in its use and controlled trials to ascertain whether MDL 17,043 is safe and efficacious in chronic severe heart failure