Hyponatremia: Current Treatment Strategies and the Role of Vasopressin Antagonists

Abstract

Objective: Hyponatremia is a complex electrolyte disorder that results mainly from dysregulation of arginine vasopressin (AVP) by osmotic and nonosmotic mechanisms. Several populations, including the elderly, are at risk for the development of hyponatremia, and awareness of such risk factors can lead to an overall improvement in patient care. AVP receptor antagonists are promising new therapeutic options whose safety and efficacy have been clinically established for some forms of hyponatremia. Data Sources: A search of MEDLINE (1967–March 2007) was conducted, using the search terms aquaporins, AVP, AVP receptor antagonists, conivaptan, hyponatremia, lixivaptan, and tolvaptan. Additionally, data were obtained from manufacturers' prescribing information. Study Selection and Data Extraction: All articles identified from the reference search and data sources were evaluated. Material was included in this review if it was relevant to the pathophysiology and management of euvolemic and hypervolemic hyponatremia in hospitalized patients. Data Synthesis: A large percentage of hospitalized patients are found to have symptomatic or asymptomatic hyponatremia. One study reported that 24.5% of intensive care patients admitted over a 3 month period experienced hyponatremia at some time during their hospitalization. Conventional management techniques include water restriction, demeclocycline, lithium, and urea, which have demonstrated variable efficacy and toxicity. AVP receptor antagonists, whose safety and efficacy have been established in clinical trials, are providing new therapeutic options. Conclusions: AVP receptor antagonists appear to be safe and effective for the treatment of patients with hyponatremia. With conivaptan recently approved by the Food and Drug Administration for use in treating euvolemic and hypervolemic hyponatremia in hospitalized patients and lixivaptan and tolvaptan in the late stages of development, prudent use of these agents requires a thorough understanding of the clinical manifestations of hyponatremia to optimize therapeutic outcomes.