Short-term Efficacy and Safety of Vasopressin Receptor Antagonists for Treatment of Hyponatremia

Abstract

Background We performed a meta-analysis to systematically measure efficacy and safety of vasopressin receptor antagonists (VRAs) tested in randomized controlled trials for treatment of hyponatremia. Methods MEDLINE, ClinicalTrials.gov, and scientific abstracts were searched without language restriction. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, and efficacy and safety endpoints. Results Eleven trials were identified (1094 patients). By meta-analysis, VRAs achieved a net increase in serum sodium concentration ([Na +] serum) relative to placebo of 3.3 mEq/L at day 1 (95% confidence interval [CI], 2.7-3.8), and 4.2 mEq/L at day 2 (95% CI, 3.6-4.8), persisting at days 3-5. Larger net increases in [Na +] serum at days 1-4 were observed in euvolemic hyponatremia and with higher doses. VRAs induced a net increase in effective water clearance relative to placebo of 1244 mL at day 1 (95% CI, 920-1567), persisting at days 2 and 4. VRAs were associated with odds ratios of 3.0 for overly rapid correction of [Na +] serum ( P <.001), 7.8 for development of hypernatremia ( P <.001), 3.3 for thirst development ( P <.001), and 2.2 for postural hypotension ( P = .04). Conclusions Short-term use of VRAs in treating hyponatremia was successful at raising [Na +] serum. Additional experience is required to guide their optimal use and minimize safety concerns.