Efficacy and safety of two different tolvaptan doses in the treatment of hyponatremia in the Emergency Department

Hyponatremia (plasma sodium concentration or P[Na(+)] <136 mEq/L) is the most common electrolyte unbalance in clinical practice. Although it constitutes a negative prognostic factor, it frequently remains underdiagnosed and undertreated. Tolvaptan is an oral V2-receptor antagonist which produces aquaresis. Given its emerging role in the treatment of dilutional hyponatremia, we aimed to compare the efficacy and safety of two different doses of this drug in an Emergency Department (ED) setting. Consecutive patients with moderate-severe euvolemic or hypervolemic hyponatremia were sequentially assigned to the 15 mg Group and to the 7.5 mg Group, and were revaluated at 6, 12 and 24 h. Further evaluations and administrations were scheduled daily until P[Na(+)] correction was achieved or the maximum period of 72 h was exceeded. A 1-month follow-up was performed. Twenty-three patients were enrolled: 12 were included in the 15 mg Group, 11 in the 7.5 mg Group. Both doses significantly elevated the P[Na(+)] over 24 h, although the 15 mg Group showed faster corrections than the 7.5 mg Group (12 vs 6 mEq/L/24 h; P = 0.025). An optimal correction rate (within 4-8 mEq/L/24 h) was observed in 45.4 % of the 7.5 mg Group against 25.0 % (P n.s.). The standard dose led to dangerous overcorrections (>12 mEq/L/24 h) in 41.7 % of the patients, while the low dose did not cause any (P = 0.037). No osmotic demyelination syndrome was observed. A 7.5 mg tolvaptan dose can be considered both effective and safe in treating hyponatremia in the ED, while a 15 mg dose implicates too high risk of overcorrection.