New agents for managing hyponatremia in hospitalized patients

PURPOSE: An overview of hyponatremia is provided, including its pathophysiology, clinical manifestations, signs and symptoms, and treatment, particularly with arginine vasopressin (AVP)-receptor antagonists. SUMMARY: Hyponatremia (generally defined as a serum sodium concentration of <135 meq/L) is one of the most common electrolyte disorders in hospitalized and clinic patients. It may be caused by a number of conditions, including infections, heart disease, surgery, malignancy, and medication use. Clinical signs and symptoms such as hallucinations, lethargy, weakness, bradycardia, respiratory depression, seizures, coma, and death have been reported. Conventional treatment consists of fluid restriction and administration of hypertonic saline and pharmacologic agents, such as demeclocycline, lithium carbonate, and urea. These treatment options are often of limited effectiveness or difficult for patients to tolerate. AVP promotes the reabsorption of water in the renal collecting ducts by activation of V(2) receptors, resulting in water retention and dilution of serum solutes. The AVP-receptor antagonists, conivaptan, lixivaptan, and tolvaptan, are being studied for the treatment of hyponatremia. Conivaptan has been shown in clinical trials to increase free-water excretion and safely normalize serum sodium concentrations in patients with hyponatremia and is well tolerated. Also in clinical trials, lixivaptan and tolvaptan have safely improved serum sodium concentrations in patients with hyponatremia. CONCLUSION: Hyponatremia is a serious health condition for which treatment should be carefully performed. As new agents for treating hyponatremia, AVP-receptor antagonists have demonstrated efficacy and safety in clinical trials and may serve as significant improvements in the current treatment options for managing this disorder.